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The immunoglobulin supergene family is "the group of proteins that have immunoglobulin-like domains, including histocompatibility antigens, the T-cell antigen receptor, poly-IgR, and other proteins involved in the vertebrate immune response (17)."<ref name=Ishioka/>
The immunoglobulin supergene family is "the group of proteins that have immunoglobulin-like domains, including histocompatibility antigens, the T-cell antigen receptor, poly-IgR, and other proteins involved in the vertebrate immune response (17)."<ref name=Ishioka/>
==𝛂<sub>1</sub>B-glycoprotein==
==Immunoglobulin supergenes==
"𝛂<sub>1</sub>B-glycoprotein(𝛂<sub>1</sub>B) [...] consists of a single polypeptide chain N-linked to four
Each family within the immunoglobulin supergene family has its share of human genes:
glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues. [...] 𝛂<sub>1</sub>B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond. [...] several domains of 𝛂<sub>1</sub>B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. 𝛂<sub>1</sub>B [...] exhibits sequence similarity to other members of the immunoglobulin supergene family such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA."<ref name=Ishioka>{{ cite journal
"Some of the domains of 𝛂<sub>1</sub>B show significant homology to variable (V) and constant (C) regions of certain immunoglobulins. Likewise, there is statistically significant homology between 𝛂<sub>1</sub>B and the secretory component (SC) of human IgA (15) and also with the extracellular portion of the rabbit receptor for transepithelial transport of polymeric immunoglobulins (IgA and IgM). Mostov et al. (16) have called the later protein the poly-Ig receptor or poly-IgR and have shown that it is the precursor of SC."<ref name=Ishioka/>
{{main|Major histocompatibility complex class I gene family}}
===Class II===
{{main|MHC class II}}
[[Image:MHC Class 2.svg|thumb|In the schematic representation MHC class II consists of two homologous peptides, an α and β chain.]]
Gene ID: 972 is [[CD74]] CD74 molecule, aka HLA class II histocompatibility antigen gamma chain, on 5q33.1: "The protein encoded by this gene associates with class II major histocompatibility complex (MHC) and is an important chaperone that regulates antigen presentation for immune response. It also serves as cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF) which, when bound to the encoded protein, initiates survival pathways and cell proliferation. This protein also interacts with amyloid precursor protein (APP) and suppresses the production of amyloid beta (Abeta). Multiple alternatively spliced transcript variants encoding different isoforms have been identified."<ref name=RefSeq2011A>{{ cite web
|author=RefSeq
|title=CD74 CD74 molecule [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=August 2011
|url=https://www.ncbi.nlm.nih.gov/gene/972
|accessdate=1 April 2020 }}</ref>
# NP_001020329.1 HLA class II histocompatibility antigen gamma chain isoform c: "Transcript Variant: This variant (3) lacks three consecutive exons in the 3' coding region, which results in a frame-shift, compared to variant 1. The resulting isoform (c) has a shorter and distinct C-terminus, compared to isoform a."<ref name=RefSeq2011A/>
# NP_001020330.1 HLA class II histocompatibility antigen gamma chain isoform a: "Transcript Variant: This variant (1) encodes the longest isoform (a)."<ref name=RefSeq2011A/>
# NP_001351012.1 HLA class II histocompatibility antigen gamma chain isoform d.<ref name=RefSeq2011A/>
# NP_001351013.1 HLA class II histocompatibility antigen gamma chain isoform e.<ref name=RefSeq2011A/>
# NP_004346.1 HLA class II histocompatibility antigen gamma chain isoform b: "Transcript Variant: This variant (2) lacks an in-frame exon in the 3' coding region, compared to variant 1. The resulting isoform (b) lacks an internal segment in the C-terminal region, compared to isoform a."<ref name=RefSeq2011A/>
Gene ID: 1302 is COL11A2 collagen type XI alpha 2 chain on 6p21.32: "This gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. It is located on chromosome 6 very close to but separate from the gene for retinoid X receptor beta. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1 type II chain. Proteolytic processing of this type XI chain produces PARP, a proline/arginine-rich protein that is an amino terminal domain. Mutations in this gene are associated with type III Stickler syndrome, otospondylomegaepiphyseal dysplasia (OSMED syndrome), Weissenbacher-Zweymuller syndrome, autosomal dominant non-syndromic sensorineural type 13 deafness (DFNA13), and autosomal recessive non-syndromic sensorineural type 53 deafness (DFNB53). Alternative splicing results in multiple transcript variants. A related pseudogene is located nearby on chromosome 6."<ref name=RefSeq1302>{{ cite web
|title=COL11A2 collagen type XI alpha 2 chain [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2009
|url=https://www.ncbi.nlm.nih.gov/gene/1302
|accessdate=7 April 2020 }}</ref>
# NP_001157243.1 collagen alpha-2(XI) chain isoform 4 precursor: "Transcript Variant: This variant (4) lacks several exons at the 3' end and has a distinct 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (4) has a distinct C-terminus and is considerably shorter than isoform 1."<ref name=RefSeq1302/>
# NP_542410.2 collagen alpha-2(XI) chain isoform 3 preproprotein: "Transcript Variant: This variant (3) lacks three alternate in-frame exons, compared to variant 1, resulting in a shorter protein (isoform 3), compared to isoform 1. There are no publicly available human transcripts representing the full-length exon combination of this variant, but the region of variation is supported by experimental data in PMIDs 8663204 and 8838804, by homology data in mouse, and the full-length sequence is represented in accession U32169.1:AAC50215.1."<ref name=RefSeq1302/>
# NP_542411.2 collagen alpha-2(XI) chain isoform 1 preproprotein: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1). There are no publicly available human transcripts representing the full-length exon combination of this variant, but the region of variation is supported by experimental data in PMIDs 8663204 and 8838804, by homology data in mouse, and the full-length sequence is represented in accession U32169.1:AAC50214.1."<ref name=RefSeq1302/>
# NP_542412.2 collagen alpha-2(XI) chain isoform 2 preproprotein: "Transcript Variant: This variant (2) lacks two alternate in-frame exons, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1. There are no publicly available human transcripts representing the full-length exon combination of this variant, but the region of variation is supported by experimental data in PMIDs 8663204 and 8838804, by homology data in mouse, and the full-length sequence is represented in accession U32169.1:AAC50213.1."<ref name=RefSeq1302/>
Gene ID: 1388 is ATF6B activating transcription factor 6 beta on 6p21.32: "The protein encoded by this gene is a transcription factor in the unfolded protein response (UPR) pathway during ER stress. Either as a homodimer or as a heterodimer with ATF6-alpha, the encoded protein binds to the ER stress response element, interacting with nuclear transcription factor Y to activate UPR target genes. The protein is normally found in the membrane of the endoplasmic reticulum; however, under ER stress, the N-terminal cytoplasmic domain is cleaved from the rest of the protein and translocates to the nucleus. Two transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq1388>{{ cite web
Gene ID: 1 A1BG [[alpha-1-B glycoprotein]] on 19q13.43: "The protein encoded by this gene is a plasma glycoprotein of unknown function. The protein shows sequence similarity to the variable regions of some immunoglobulin supergene family member proteins."<ref name=RefSeq1>{{ cite web
|title=A1BG alpha-1-B glycoprotein [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=October 2008
|url=https://www.ncbi.nlm.nih.gov/gene/1388
|accessdate=8 April 2020 }}</ref>
# NP_001129625.1 cyclic AMP-dependent transcription factor ATF-6 beta isoform b: "Transcript Variant: This variant (2) uses an alternate in-frame splice site at the 3' end of exon 1 compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is 3 aa shorter compared to isoform a."<ref name=RefSeq1388/>
# NP_004372.3 cyclic AMP-dependent transcription factor ATF-6 beta isoform a: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a)."<ref name=RefSeq1388/>
Gene ID: 1616 is [[Death-associated protein 6|DAXX death domain associated protein]] on 6p21.32: "This gene encodes a multifunctional protein that resides in multiple locations in the nucleus and in the cytoplasm. It interacts with a wide variety of proteins, such as apoptosis antigen Fas, centromere protein C, and transcription factor erythroblastosis virus E26 oncogene homolog 1. In the nucleus, the encoded protein functions as a potent transcription repressor that binds to sumoylated transcription factors. Its repression can be relieved by the sequestration of this protein into promyelocytic leukemia nuclear bodies or nucleoli. This protein also associates with centromeres in G2 phase. In the cytoplasm, the encoded protein may function to regulate apoptosis. The subcellular localization and function of this protein are modulated by post-translational modifications, including sumoylation, phosphorylation and polyubiquitination. Alternative splicing results in multiple transcript variants."<ref name=RefSeq1616>{{ cite web
|author=RefSeq
|title=DAXX death domain associated protein [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=November 2008
|url=https://www.ncbi.nlm.nih.gov/gene/1616
|accessdate=8 April 2020 }}</ref>
# NP_001135441.1 death domain-associated protein 6 isoform a: "Transcript Variant: This variant (1) represents the longest transcript but encodes the shorter isoform (a). Variants 1 and 2 encode the same isoform (a)."<ref name=RefSeq1616/>
# NP_001135442.1 death domain-associated protein 6 isoform b: "Transcript Variant: This variant (3) lacks an in-frame segment in a 5' coding exon and uses an upstream start codon, compared to variant 1. The resulting protein (isoform b) has a distinct and longer N-terminus, compared to isoform a."<ref name=RefSeq1616/>
# NP_001241646.1 death domain-associated protein 6 isoform c: "Transcript Variant: This variant (4) differs in the 5' UTR and lacks an exon in the coding region, compared to variant 1. These differences cause translation initiation at a downstream AUG and result in an isoform (c) with a shorter N-terminus, compared to isoform a."<ref name=RefSeq1616/>
# NP_001341.1 death domain-associated protein 6 isoform a: "Transcript Variant: This variant (2) uses an alternate splice site in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (a)."<ref name=RefSeq1616/>
Gene ID: 2968 is [[GTF2H4]] general transcription factor IIH subunit 4 on 6p21.33.<ref name=RefSeq2968>{{ cite web
|author=RefSeq
|title=GTF2H4 general transcription factor IIH subunit 4 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=13 March 2020
|url=https://www.ncbi.nlm.nih.gov/gene/2968
|accessdate=6 April 2020 }}</ref>
Gene ID: 3108 is [[HLA-DMA]] major histocompatibility complex, class II, DM alpha, on 6p21.32: "HLA-DMA belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta chain (DMB), both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail."<ref name=RefSeq3108>{{ cite web
|author=RefSeq
|title=HLA-DMA major histocompatibility complex, class II, DM alpha [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/3108
|url=https://www.ncbi.nlm.nih.gov/gene/1
|accessdate=2 April 2020 }}</ref>
|accessdate=17 April 2020 }}</ref>
# NP_006111.2 HLA class II histocompatibility antigen, DM alpha chain precursor.<ref name=RefSeq3108/>
# NP_570602.2 alpha-1B-glycoprotein precursor, Conserved Domains (4) summary: '''cd05751''' Location: 401 → 493 Ig1_LILRB1_like; First immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors (LILR)B1 (also known as LIR-1) and similar proteins, '''smart00410''' Location: 218 → 280 IG_like; Immunoglobulin like, '''pfam13895''' Location: 210 → 301 Ig_2; Immunoglobulin domain and '''cl11960''' Location: 28 → 110 Ig; Immunoglobulin domain.<ref name=RefSeq1/>
Gene ID: 3109 is [[HLA-DMB]] major histocompatibility complex, class II, DM beta, on 6p21.32: "HLA-DMB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta (DMB) chain, both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP (class II-associated invariant chain peptide) molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail."<ref name=RefSeq2008July>{{ cite web
A1BG contains the immunoglobulin domain: '''cl11960''' and three immunoglobulin-like domains: '''pfam13895''', '''cd05751''' and '''smart00410'''.
|author=RefSeq
|title=HLA-DMB major histocompatibility complex, class II, DM beta [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/3109
|accessdate=2 April 2020 }}</ref>
# NP_002109.2 HLA class II histocompatibility antigen, DM beta chain precursor.<ref name=RefSeq2008July/>
Gene ID: 3111 is [[HLA-DOA]] major histocompatibility complex, class II, DO alpha, on 6p21.32: "HLA-DOA belongs to the HLA class II alpha chain paralogues. HLA-DOA forms a heterodimer with HLA-DOB. The heterodimer, HLA-DO, is found in lysosomes in B cells and regulates HLA-DM-mediated peptide loading on MHC class II molecules. In comparison with classical HLA class II molecules, this gene exhibits very little sequence variation, especially at the protein level."<ref name=RefSeq3111>{{ cite web
"Immunoglobulin (Ig) domain ['''cl11960'''] found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond."<ref name=NCBI386229>{{ cite web
|author=RefSeq
|author=NCBI
|title=HLA-DOA major histocompatibility complex, class II, DO alpha [ Homo sapiens (human) ]
|title=Conserved Protein Domain Family cl11960: Ig Superfamily
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
# NP_002110.1 HLA class II histocompatibility antigen, DO alpha chain precursor.<ref name=RefSeq3111/>
Gene ID: 3112 is [[HLA-DOB]] major histocompatibility complex, class II, DO beta, on 6p21.32: "HLA-DOB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DOA) and a beta chain (DOB), both anchored in the membrane. It is located in intracellular vesicles. DO suppresses peptide loading of MHC class II molecules by inhibiting HLA-DM. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail."<ref name=RefSeq3112>{{ cite web
"This domain ['''pfam13895'''] contains immunoglobulin-like domains."<ref name=NCBI372793>{{ cite web
|author=RefSeq
|author=NCBI
|title=HLA-DOB major histocompatibility complex, class II, DO beta [ Homo sapiens (human) ]
|title=Conserved Protein Domain Family pfam13895: Ig_2
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
# NP_002111.1 HLA class II histocompatibility antigen, DO beta chain precursor.<ref name=RefSeq3112/>
Gene ID: 3113 is HLA-DPA1 [[major histocompatibility complex, class II, DP alpha 1]] on 6p21.32: "HLA-DPA1 belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta (DPB) chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules."<ref name=RefSeq2008Ju>{{ cite web
"Ig1_LILR_KIR_like: ['''cd05751'''] domain similar to the first immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors (LILRs) and Natural killer inhibitory receptors (KIRs). This group includes LILRB1 (or LIR-1), LILRA5 (or LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (or CD89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3,and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1 (LIR-1), LILRB2 (LIR-2), and LILRB3 (LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LIR-1 (LILRB1), and LIR-2 (LILRB2), show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1 (LIR-1), and LILRB2 (LIR-2), and two in the case of LILRB4 (LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst."<ref name=NCBI319306>{{ cite web
|author=RefSeq
|author=NCBI
|title=HLA-DPA1 major histocompatibility complex, class II, DP alpha 1 [ Homo sapiens (human) ]
|title=Conserved Protein Domain Family cd05751: Ig1_LILR_KIR_like
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
# NP_001229453.1 HLA class II histocompatibility antigen, DP alpha 1 chain precursor: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein."<ref name=RefSeq2008Ju/>
# NP_001229454.1 HLA class II histocompatibility antigen, DP alpha 1 chain precursor: "Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein."<ref name=RefSeq2008Ju/>
# NP_291032.2 HLA class II histocompatibility antigen, DP alpha 1 chain precursor: "Transcript Variant: This variant (1) represents the shortest transcript. Variants 1, 2 and 3 encode the same protein."<ref name=RefSeq2008Ju/>
Gene ID: 3115 is [[HLA-DPB1]] major histocompatibility complex, class II, DP beta 1, on 6p21.32: "HLA-DPB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta chain (DPB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules."<ref name=RefSeq2008DP>{{ cite web
"IG domains ['''smart00410'''] that cannot be classified into one of IGv1, IGc1, IGc2, IG."<ref name=NCBI214653>{{ cite web
|author=RefSeq
|author=NCBI
|title=HLA-DPB1 major histocompatibility complex, class II, DP beta 1 [ Homo sapiens (human) ]
|title=Conserved Protein Domain Family smart00410: IG_like
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
# NP_002112.3 HLA class II histocompatibility antigen, DP beta 1 chain precursor.<ref name=RefSeq2008DP/>
"𝛂<sub>1</sub>B-glycoprotein(𝛂<sub>1</sub>B) [...] consists of a single polypeptide chain N-linked to four
glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues. [...] 𝛂<sub>1</sub>B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond. [...] several domains of 𝛂<sub>1</sub>B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. 𝛂<sub>1</sub>B [...] exhibits sequence similarity to other members of the immunoglobulin supergene family such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA."<ref name=Ishioka>{{ cite journal
|author=Noriaki Ishioka, Nobuhiro Takahashi, and Frank W. Putnam
|title=Amino acid sequence of human plasma 𝛂<sub>1</sub>B-glycoprotein: Homology to the immunoglobulin supergene family
|journal=Proceedings of the National Academy of Sciences USA
Gene ID: 3117 is [[HLA-DQA1]] major histocompatibility complex, class II, DQ alpha 1, on 6p21.32: "HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation."<ref name=RefSeq2008DQ>{{ cite web
"Some of the domains of 𝛂<sub>1</sub>B show significant homology to variable (V) and constant (C) regions of certain immunoglobulins. Likewise, there is statistically significant homology between 𝛂<sub>1</sub>B and the secretory component (SC) of human IgA (15) and also with the extracellular portion of the rabbit receptor for transepithelial transport of polymeric immunoglobulins (IgA and IgM). Mostov et al. (16) have called the later protein the poly-Ig receptor or poly-IgR and have shown that it is the precursor of SC."<ref name=Ishioka/>
|author=RefSeq
|title=HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/3117
|accessdate=28 March 2020 }}</ref>
# NP_002113.2 HLA class II histocompatibility antigen, DQ alpha 1 chain precursor.<ref name=RefSeq2008DQ/>
Gene ID: 3118 is [[HLA-DQA2]] major histocompatibility complex, class II, DQ alpha 2, on 6p21.32: "This gene belongs to the HLA class II alpha chain family. The encoded protein forms a heterodimer with a class II beta chain. It is located in intracellular vesicles and plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (B lymphocytes, dendritic cells, macrophages) and are used to present antigenic peptides on the cell surface to be recognized by CD4 T-cells."<ref name=RefSeq2010J>{{ cite web
Gene ID: 7441 is [[VPREB1]] V-set pre-B cell surrogate light chain 1 on 22q11.22: "The protein encoded by this gene belongs to the immunoglobulin superfamily and is expressed selectively at the early stages of B cell development, namely, in proB and early preB cells. This gene encodes the iota polypeptide chain that is associated with the Ig-mu chain to form a molecular complex which is expressed on the surface of pre-B cells. The complex is thought to regulate Ig gene rearrangements in the early steps of B-cell differentiation. Alternative splicing results in multiple transcript variants."<ref name=RefSeq7441>{{ cite web
|author=RefSeq
|author=RefSeq
|title=HLA-DQA2 major histocompatibility complex, class II, DQ alpha 2 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=June 2010
|date=January 2015
|url=https://www.ncbi.nlm.nih.gov/gene/3118
|url=https://www.ncbi.nlm.nih.gov/gene/7441
|accessdate=2 April 2020 }}</ref>
|accessdate=17 April 2020 }}</ref>
# NP_064440.1 HLA class II histocompatibility antigen, DQ alpha 2 chain precursor.<ref name=RefSeq2010J/>
# NP_001290438.1 immunoglobulin iota chain isoform 2: "Transcript Variant: This variant (2) uses an alternate splice site in the coding region and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1."<ref name=RefSeq7441/> Conserved Domains summary: '''smart00410''' Location: 25 → 115 IG_like; Immunoglobulin like and '''cl11960''' Location: 29 → 117 Ig; Immunoglobulin domain.<ref name=RefSeq7441/>
# NP_009059.1 immunoglobulin iota chain isoform 1 precursor: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."<ref name=RefSeq7441/> Conserved Domains summary: '''smart00410''' Location: 26 → 116 IG_like; Immunoglobulin like and '''cl11960''' Location: 30 → 118 Ig; Immunoglobulin domain.<ref name=RefSeq7441/>
Gene ID: 3119 is [[HLA-DQB1]] major histocompatibility complex, class II, DQ beta 1, on 6p21.32: "HLA-DQB1 belongs to the HLA class II beta chain paralogs. This class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and it contains six exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. Alternative splicing results in multiple transcript variants."<ref name=RefSeq2011>{{ cite web
Gene ID: 29802 is [[VPREB3]] V-set pre-B cell surrogate light chain 3 on 22q11.23; 22q11: "The protein encoded by this gene is the human ortholog of the mouse VpreB3 (8HS20) protein, is thought to be involved in B-cell maturation, and may play a role in assembly of the pre-B cell receptor (pre-BCR). While the role of this protein in B-cell development has not yet been elucidated, studies with the chicken ortholog of this protein have found that when overexpressed, this protein localizes to the endoplasmic reticulum. The mouse ortholog of this protein has been shown to associate with membrane mu heavy chains early in the course of pre-B cell receptor biosynthesis. Expression of this gene has been observed in some lymphomas."<ref name=RefSeq29802>{{ cite web
|author=RefSeq
|author=RefSeq
|title=HLA-DQB1 major histocompatibility complex, class II, DQ beta 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=September 2011
|date=April 2015
|url=https://www.ncbi.nlm.nih.gov/gene/3119
|url=https://www.ncbi.nlm.nih.gov/gene/29802
|accessdate=28 March 2020 }}</ref>
|accessdate=17 April 2020 }}</ref>
# NP_001230890.1 HLA class II histocompatibility antigen, DQ beta 1 chain isoform 2 precursor: "Transcript Variant: This variant (2) includes an alternate in-frame exon in the coding region, compared to variant 1. It encodes isoform 2 which is longer than isoform 1. This transcript represents the DQB1*06:02:01:01 allele of the HLA-DQB1 gene, as represented in the assembled chromosome 6 in the primary assembly of the reference genome."<ref name=RefSeq2011/>
# NP_001230891.1 HLA class II histocompatibility antigen, DQ beta 1 chain isoform 1 precursor: "Transcript Variant: This variant (3) has the same exon combination as variant 1 but represents the DQB1*02:01:01:01 allele of the HLA-DQB1 gene, as represented in the alternate locus group ALT_REF_LOCI_2 of the reference genome. It encodes isoform 1."<ref name=RefSeq2011/>
# NP_002114.3 HLA class II histocompatibility antigen, DQ beta 1 chain isoform 1 precursor: "Transcript Variant: This variant (1) is the predominant transcript and encodes isoform 1. This transcript represents the DQB1*06:02:01:01 allele of the HLA-DQB1 gene, as represented in the assembled chromosome 6 in the primary assembly of the reference genome."<ref name=RefSeq2011/>
Gene ID: 3120 is [[HLA-DQB2]] major histocompatibility complex, class II, DQ beta 2, on 6p21.32: "HLA-DQB2 belongs to the family of HLA class II beta chain paralogs. Class II molecules are heterodimers consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. They play a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). Polymorphisms in the alpha and beta chains specify the peptide binding specificity, and typing for these polymorphisms is routinely done for bone marrow transplantation. However this gene, HLA-DQB2, is not routinely typed, as it is not thought to have an effect on transplantation. There is conflicting evidence in the literature and public sequence databases for the protein-coding capacity of HLA-DQB2. Because there is evidence of transcription and an intact ORF, HLA-DQB2 is represented in Entrez Gene and in RefSeq as a protein-coding locus."<ref name=RefSeq2010>{{ cite web
==Carcinoembryonic antigen gene family==
|author=RefSeq
{{main|Carcinoembryonic antigen gene family}}
|title=HLA-DQB2 major histocompatibility complex, class II, DQ beta 2 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=October 2010
|url=https://www.ncbi.nlm.nih.gov/gene/3120
|accessdate=2 April 2020 }}</ref>
# NP_001185787.1 HLA class II histocompatibility antigen, DQ beta 2 chain isoform 2 precursor: "Transcript Variant: This variant (2) lacks an in-frame exon in the 3' coding region, compared to variant 1. It encodes a shorter isoform (2), compared to isoform 1."<ref name=RefSeq2010/>
# NP_001287719.1 HLA class II histocompatibility antigen, DQ beta 2 chain isoform 1 precursor: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."<ref name=RefSeq2010/>
Gene ID: 3121 is HLA-DQB3 major histocompatibility complex, class II, DQ beta 3, on 6p21.3: "not in current annotation release"<ref name=RefSeq3121>{{ cite web
==Immunoglobulin superfamily genes==
|author=RefSeq
{{main|Immunoglobulin superfamily genes}}
|title=HLA-DQB3 major histocompatibility complex, class II, DQ beta 3 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=24 March 2019
|url=https://www.ncbi.nlm.nih.gov/gene/3121
|accessdate=5 April 2020 }}</ref>
Gene ID: 3122 is [[HLA-DRA]] major histocompatibility complex, class II, DR alpha, on 6p21.32: "HLA-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha and a beta chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5."<ref name=RefSeq2008J>{{ cite web
==Major histocompatibility complex genes==
|author=RefSeq
{{main|Major histocompatibility complex}}
|title=HLA-DRA major histocompatibility complex, class II, DR alpha [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/3122
|accessdate=30 March 2020 }}</ref>
#NP_061984.2 HLA class II histocompatibility antigen, DR alpha chain precursor.<ref name=RefSeq2008J/>
Gene ID: 3123 is [[HLA-DRB1]] major histocompatibility complex, class II, DR beta 1, on 6p21.32: "HLA-DRB1 belongs to the HLA class II beta chain paralogs. The class II molecule is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells. The beta chain is approximately 26-28 kDa. It is encoded by 6 exons. Exon one encodes the leader peptide; exons 2 and 3 encode the two extracellular domains; exon 4 encodes the transmembrane domain; and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Hundreds of DRB1 alleles have been described and some alleles have increased frequencies associated with certain diseases. There are multiple pseudogenes of this gene."<ref name=RefSeq2020>{{ cite web
===Class I===
|author=RefSeq
{{main|MHC class I}}
|title=HLA-DRB1 major histocompatibility complex, class II, DR beta 1 [ Homo sapiens (human) ]
{{main|Major histocompatibility complex class I gene family}}
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=February 2020
|url=https://www.ncbi.nlm.nih.gov/gene/3123
|accessdate=28 March 2020 }}</ref>
# NP_001230894.1 major histocompatibility complex, class II, DR beta 1 precursor precursor: "Transcript Variant: This variant (2) represents the DRB1*03:01:01 allele of the HLA-DRB1 gene, as represented in the alternate locus groups ALT_REF_LOCI_2 and ALT_REF_LOCI_6 of the reference genome."<ref name=RefSeq2020/>
# NP_001346122.1 major histocompatibility complex, class II, DR beta 1 precursor: "Transcript Variant: This variant (3) represents the DRB1*07:01:01 allele of the HLA-DRB1 gene, as represented in the alternate locus groups ALT_REF_LOCI_3 and ALT_REF_LOCI_4 of the reference genome."<ref name=RefSeq2020/>
# NP_001346123.1 major histocompatibility complex, class II, DR beta 1 precursor: "Transcript Variant: This variant (4) represents the DRB1*04:03:01 allele of the HLA-DRB1 gene, as represented in the alternate locus group ALT_REF_LOCI_7 of the reference genome."<ref name=RefSeq2020/>
# NP_002115.2 major histocompatibility complex, class II, DR beta 1 precursor precursor: "Transcript Variant: This variant (1) represents the DRB1*15:01:01 allele of the HLA-DRB1 gene, as represented in the assembled chromosome 6 in the primary assembly of the reference genome and the CHM1_1.1 genome."<ref name=RefSeq2020/>
Gene ID: 3125 is [[HLA-DRB3]] major histocompatibility complex, class II, DR beta 3, on 6p21.3: "HLA-DRB3 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DRA) and a beta (DRB) chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells. The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. There are multiple pseudogenes of this gene."<ref name=RefSeq2020F>{{ cite web
===Class II===
|author=RefSeq
{{main|MHC class II}}
|title=HLA-DRB3 major histocompatibility complex, class II, DR beta 3 [ Homo sapiens (human) ]
{{main|Major histocompatibility complex class II gene family}}
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=February 2020
|url=https://www.ncbi.nlm.nih.gov/gene/3125
|accessdate=30 March 2020 }}</ref>
# NP_072049.2 major histocompatibility complex, class II, DR beta 3 precursor.<ref name=RefSeq2020F/>
Gene ID: 3126 is [[HLA-DRB4]] major histocompatibility complex, class II, DR beta 4, on 6p21.3: "HLA-DRB4 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DRA) and a beta (DRB) chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells. The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. There are multiple pseudogenes of this gene."<ref name=RefSeq2020DR>{{ cite web
|author=RefSeq
|title=HLA-DRB4 major histocompatibility complex, class II, DR beta 4 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=February 2020
|url=https://www.ncbi.nlm.nih.gov/gene/3126
|accessdate=28 March 2020 }}</ref>
# NP_068818.4 major histocompatibility complex, class II, DR beta 4 precursor.<ref name=RefSeq2020DR/>
Gene ID: 3127 is [[HLA-DRB5]] major histocompatibility complex, class II, DR beta 5, on 6p21.32: "HLA-DRB5 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DRA) and a beta (DRB) chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells. The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. There are multiple pseudogenes of this gene."<ref name=RefSeq2020Fe>{{ cite web
|author=RefSeq
|title=HLA-DRB5 major histocompatibility complex, class II, DR beta 5 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=February 2020
|url=https://www.ncbi.nlm.nih.gov/gene/3127
|accessdate=30 March 2020 }}</ref>
# NP_002116.2 major histocompatibility complex, class II, DR beta 5 precursor.<ref name=RefSeq2020Fe/>
Gene ID: 3833 is KIFC1 kinesin family member C1 on 6p21.32.<ref name=RefSeq3833>{{ cite web
|author=RefSeq
|title=KIFC1 kinesin family member C1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=5 April 2020
|url=https://www.ncbi.nlm.nih.gov/gene/3833
|accessdate=9 April 2020 }}</ref>
Gene ID: 4261 is [[CIITA]] class II major histocompatibility complex transactivator on 16p13.13: "This gene encodes a protein with an acidic transcriptional activation domain, 4 LRRs (leucine-rich repeats) and a GTP binding domain. The protein is located in the nucleus and acts as a positive regulator of class II major histocompatibility complex gene transcription, and is referred to as the "master control factor" for the expression of these genes. The protein also binds GTP and uses GTP binding to facilitate its own transport into the nucleus. Once in the nucleus it does not bind DNA but rather uses an intrinsic acetyltransferase (AT) activity to act in a coactivator-like fashion. Mutations in this gene have been associated with bare lymphocyte syndrome type II (also known as hereditary MHC class II deficiency or HLA class II-deficient combined immunodeficiency), increased susceptibility to rheumatoid arthritis, multiple sclerosis, and possibly myocardial infarction. Several transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq2013>{{ cite web
|author=RefSeq
|title=CIITA class II major histocompatibility complex transactivator [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=November 2013
|url=https://www.ncbi.nlm.nih.gov/gene/2623
|accessdate=30 March 2020 }}</ref>
# NP_000237.2 MHC class II transactivator isoform 2: "Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the 5' end of an exon compared to variant 1. The resulting isoform (2) is 1 aa shorter compared to isoform 1."<ref name=RefSeq2013/>
# NP_001273331.1 MHC class II transactivator isoform 1: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."<ref name=RefSeq2013/>
# NP_001273332.1 MHC class II transactivator isoform 3: "Transcript Variant: This variant (3) uses two alternate splice junctions and lacks two alternate coding exons compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1."<ref name=RefSeq2013/>
# NR_104444.2 RNA Sequence: "Transcript Variant: This variant (4) uses an alternate splice junction and lacks an alternate exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD)."<ref name=RefSeq2013/>
Gene ID: 4904 is YBX1 [[Y box binding protein 1|Y-box binding protein 1]] aka CCAAT-binding transcription factor I subunit A, DNA-binding protein B, Y-box transcription factor, enhancer factor I subunit A, major histocompatibility complex, class II, Y box-binding protein I, nuclease-sensitive element-binding protein 1 on 1p34.2: "This gene encodes a highly conserved cold shock domain protein that has broad nucleic acid binding properties. The encoded protein functions as both a DNA and RNA binding protein and has been implicated in numerous cellular processes including regulation of transcription and translation, pre-mRNA splicing, DNA reparation and mRNA packaging. This protein is also a component of messenger ribonucleoprotein (mRNP) complexes and may have a role in microRNA processing. This protein can be secreted through non-classical pathways and functions as an extracellular mitogen. Aberrant expression of the gene is associated with cancer proliferation in numerous tissues. This gene may be a prognostic marker for poor outcome and drug resistance in certain cancers. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on multiple chromosomes."<ref name=RefSeq4904>{{ cite web
|author=RefSeq
|title=YBX1 Y-box binding protein 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=September 2015
|url=https://www.ncbi.nlm.nih.gov/gene/4904
|accessdate=19 November 2018 }}</ref>
# NP_004550.2 Y-box-binding protein 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the functional protein."<ref name=RefSeq4904/>
# NR_132737.2 RNA Sequence: "Transcript Variant: This variant (2) contains an alternate 5' exon and lacks an internal exon, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria."<ref name=RefSeq4904/>
Gene ID: 5089 is PBX2 PBX homeobox 2 on 6p21.32: "This gene encodes a ubiquitously expressed member of the TALE/PBX homeobox family. It was identified by its similarity to a homeobox gene which is involved in t(1;19) translocation in acute pre-B-cell leukemias. This protein is a transcriptional activator which binds to the TLX1 promoter. The gene is located within the major histocompatibility complex (MHC) on chromosome 6."<ref name=RefSeq5089>{{ cite web
|author=RefSeq
|title=PBX2 PBX homeobox 2 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/5089
|accessdate=9 April 2020 }}</ref>
Gene ID: 5252 is PHF1 PHD finger protein 1 on 6p21.32: "This gene encodes a Polycomb group protein. The protein is a component of a histone H3 lysine-27 (H3K27)-specific methyltransferase complex, and functions in transcriptional repression of homeotic genes. The protein is also recruited to double-strand breaks, and reduced protein levels results in X-ray sensitivity and increased homologous recombination. Multiple transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq5252>{{ cite web
|author=RefSeq
|title=PHF1 PHD finger protein 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=May 2009
|url=https://www.ncbi.nlm.nih.gov/gene/5252
|accessdate=9 April 2020 }}</ref>
# NP_002627.2 PHD finger protein 1 isoform a: "Transcript Variant: This variant (1), uses an alternate splice site and lacks an alternate exon in the 3' coding region resulting in a frameshift, compared to variant 2. The resulting isoform (a) has a shorter and distinct C-terminus, compared to isoform b."<ref name=RefSeq5252/>
# NP_077084.2 PHD finger protein 1 isoform b: "Transcript Variant: This variant (2), also called variant PHF2, represents the longest transcript and encodes the longer isoform (b)."<ref name=RefSeq5252/>
Gene ID: 5696 is PSMB8 proteasome 20S subunit beta 8 on 6p21.32: "The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 3 (proteasome beta 5 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. Two alternative transcripts encoding two isoforms have been identified; both isoforms are processed to yield the same mature subunit."<ref name=RefSeq5696>{{ cite web
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/5696
|accessdate=9 April 2020 }}</ref>
# NP_004150.1 proteasome subunit beta type-8 isoform E1: "Transcript Variant: This variant (1) represents the longer transcript but encodes the shorter isoform (E1)."<ref name=RefSeq5696/>
# NP_683720.2 proteasome subunit beta type-8 isoform E2 precursor: "Transcript Variant: This variant (2) differs in the 5' UTR and contains an alternate in-frame exon in the 5' coding region, compared to variant 1. Isoform E2 has a distinct N-terminus, compared to isoform E1."<ref name=RefSeq5696/>
Gene ID: 5698 is PSMB9 proteasome 20S subunit beta 9 on 6p21.32: "The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 1 (proteasome beta 6 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit."<ref name=RefSeq5698>{{ cite web
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=March 2010
|url=https://www.ncbi.nlm.nih.gov/gene/5698
|accessdate=9 April 2020 }}</ref>
Gene ID: 5863 is RGL2 ral guanine nucleotide dissociation stimulator like 2 on 6p21.32.<ref name=RefSeq5863>{{ cite web
|author=RefSeq
|title=RGL2 ral guanine nucleotide dissociation stimulator like 2 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=20 March 2020
|url=https://www.ncbi.nlm.nih.gov/gene/5863
|accessdate=9 April 2020 }}</ref>
# NP_001230667.1 ral guanine nucleotide dissociation stimulator-like 2 isoform 2: "Transcript Variant: This variant (2) lacks an internal exon and uses a downstream, in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1."<ref name=RefSeq5863/>
# NP_004752.1 ral guanine nucleotide dissociation stimulator-like 2 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."<ref name=RefSeq5863/>
Gene ID: 6015 is RING1 ring finger protein 1 on 6p21.32: "This gene belongs to the RING finger family, members of which encode proteins characterized by a RING domain, a zinc-binding motif related to the zinc finger domain. The gene product can bind DNA and can act as a transcriptional repressor. It is associated with the multimeric polycomb group protein complex. The gene product interacts with the polycomb group proteins BMI1, EDR1, and CBX4, and colocalizes with these proteins in large nuclear domains. It interacts with the CBX4 protein via its glycine-rich C-terminal domain. The gene maps to the HLA class II region, where it is contiguous with the RING finger genes FABGL and HKE4."<ref name=RefSeq6015>{{ cite web
|author=RefSeq
|title=RING1 ring finger protein 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/6015
|accessdate=10 April 2020 }}</ref>
Gene ID: 6046 is BRD2 bromodomain containing 2 on 6p21.32: "This gene encodes a transcriptional regulator that belongs to the BET (bromodomains and extra terminal domain) family of proteins. This protein associates with transcription complexes and with acetylated chromatin during mitosis, and it selectively binds to the acetylated lysine-12 residue of histone H4 via its two bromodomains. The gene maps to the major histocompatability complex (MHC) class II region on chromosome 6p21.3, but sequence comparison suggests that the protein is not involved in the immune response. This gene has been implicated in juvenile myoclonic epilepsy, a common form of epilepsy that becomes apparent in adolescence. Multiple alternatively spliced variants have been described for this gene."<ref name=RefSeq6046>{{ cite web
|author=RefSeq
|title=BRD2 bromodomain containing 2 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=December 2010
|url=https://www.ncbi.nlm.nih.gov/gene/6046
|accessdate=10 April 2020 }}</ref>
# NP_001106653.1 bromodomain-containing protein 2 isoform 1: "Transcript Variant: This variant (2) has an alternate 5' UTR compared to variant 1. Both variants 1 and 2 encode the same isoform (1)."<ref name=RefSeq6046/>
# NP_001186384.1 bromodomain-containing protein 2 isoform 2: "Transcript Variant: This variant (3) has an additional in-frame exon in the CDS compared to variant 1. The resulting isoform (2) is longer than isoform 1."<ref name=RefSeq6046/>
# NP_001186385.1 bromodomain-containing protein 2 isoform 3: "Transcript Variant: This variant (4) has an alternate 5' exon, resulting in a downstream AUG start codon compared to variant 1. The resulting isoform (3) is shorter at the N-terminus, as compared to isoform 1."<ref name=RefSeq6046/>
# NP_001278915.1 bromodomain-containing protein 2 isoform 4: "Transcript Variant: This variant (5) has an alternate 5' exon and an additional internal exon compared to variant 1. The resulting isoform (4) is shorter at the N-terminus compared to isoform 1."<ref name=RefSeq6046/>
# NP_005095.1 bromodomain-containing protein 2 isoform 1: "Transcript Variant: This variant (1) and variant 2 encode the same predominant isoform (1)."<ref name=RefSeq6046/>
Gene ID: 6048 is RNF5 ring finger protein 5 on 6p21.32: "The protein encoded by this gene contains a RING finger, which is a motif known to be involved in protein-protein interactions. This protein is a membrane-bound ubiquitin ligase. It can regulate cell motility by targeting paxillin ubiquitination and altering the distribution and localization of paxillin in cytoplasm and cell focal adhesions."<ref name=RefSeq6048>{{ cite web
|author=RefSeq
|title=RNF5 ring finger protein 5 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/6048
|accessdate=10 April 2020 }}</ref>
Gene ID: 6222 is RPS18 ribosomal protein S18 on 6p21.32: "Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S13P family of ribosomal proteins. It is located in the cytoplasm. The gene product of the E. coli ortholog (ribosomal protein S13) is involved in the binding of fMet-tRNA, and thus, in the initiation of translation. This gene is an ortholog of mouse Ke3. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome."<ref name=RefSeq6222>{{ cite web
|author=RefSeq
|title=RPS18 ribosomal protein S18 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/6222
|accessdate=10 April 2020 }}</ref>
Gene ID: 6257 is RXRB retinoid X receptor beta on 6p21.32: "This gene encodes a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the effects of retinoic acid (RA). The encoded protein forms homodimers with the retinoic acid, thyroid hormone, and vitamin D receptors, increasing both DNA binding and transcriptional function on their respective response elements. This gene lies within the major histocompatibility complex (MHC) class II region on chromosome 6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene."<ref name=RefSeq6257>{{ cite web
|author=RefSeq
|title=RXRB retinoid X receptor beta [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/6257
|accessdate=10 April 2020 }}</ref>
# NP_001257330.1 retinoic acid receptor RXR-beta isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."<ref name=RefSeq6257/>
# NP_001278918.1 retinoic acid receptor RXR-beta isoform 3: "Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) has a shorter and distinct N-terminus compared to isoform 1."<ref name=RefSeq6257/>
# NP_068811.1 retinoic acid receptor RXR-beta isoform 2: "Transcript Variant: This variant (2) uses an alternate splice site in the coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1."<ref name=RefSeq6257/>
Gene ID: 6293 is VPS52 VPS52 subunit of GARP complex on 6p21.32: "This gene encodes a protein that is similar to the yeast suppressor of actin mutations 2 gene. The yeast protein forms a subunit of the tetrameric Golgi-associated retrograde protein complex that is involved in vesicle trafficking from from both early and late endosomes, back to the trans-Golgi network. This gene is located on chromosome 6 in a head-to-head orientation with the gene encoding ribosomal protein S18. Alternative splicing results in multiple transcript variants."<ref name=RefSeq6293>{{ cite web
|author=RefSeq
|title=VPS52 VPS52 subunit of GARP complex [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=January 2014
|url=https://www.ncbi.nlm.nih.gov/gene/6293
|accessdate=10 April 2020 }}</ref>
# NP_001276103.1 vacuolar protein sorting-associated protein 52 homolog isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR, initiates translation at an alternate start codon and lacks an alternate exon in the 5' coding region, compared to variant 1. It encodes isoform 2, which is shorter and has a distinct N-terminus, compared to isoform 1."<ref name=RefSeq6293/>
# NP_001276104.1 vacuolar protein sorting-associated protein 52 homolog isoform 3: "Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon, compared to variant 1. It encodes isoform 3, which is shorter at the N-terminus, compared to isoform 1."<ref name=RefSeq6293/>
# NP_001276105.1 vacuolar protein sorting-associated protein 52 homolog isoform 4: "Transcript Variant: This variant (4) differs in the 5' UTR and the 5' coding region and initiates translation at a downstream start codon, compared to variant 1. It encodes isoform 4, which is shorter than isoform 1."<ref name=RefSeq6293/>
# NP_072047.4 vacuolar protein sorting-associated protein 52 homolog isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1)."<ref name=RefSeq6293/>
Gene ID: 7922 is SLC39A7 solute carrier family 39 member 7 on 6p21.32: "The protein encoded by this gene transports zinc from the Golgi and endoplasmic reticulum to the cytoplasm. This transport may be important for activation of tyrosine kinases, some of which could be involved in cancer progression. Therefore, modulation of the encoded protein could be useful as a therapeutic agent against cancer. Alternative splicing results in multiple transcript variants."<ref name=RefSeq7922>{{ cite web
|author=RefSeq
|title=SLC39A7 solute carrier family 39 member 7 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=January 2014
|url=https://www.ncbi.nlm.nih.gov/gene/7922
|accessdate=11 April 2020 }}</ref>
# NP_001070984.1 zinc transporter SLC39A7 isoform 1 precursor: "Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1 and 2 encode the same protein (isoform 1)."<ref name=RefSeq7922/>
# NP_001275706.1 zinc transporter SLC39A7 isoform 2: "Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. It encodes isoform 2, which contains a shorter N-terminus, compared to isoform 1."<ref name=RefSeq7922/>
# NP_008910.2 zinc transporter SLC39A7 isoform 1 precursor: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Variants 1 and 2 encode the same protein."<ref name=RefSeq7922/>
Gene ID: 7923 is HSD17B8 hydroxysteroid 17-beta dehydrogenase 8 on 6p21.32: "In mice, the Ke6 protein is a 17-beta-hydroxysteroid dehydrogenase that can regulate the concentration of biologically active estrogens and androgens. It is preferentially an oxidative enzyme and inactivates estradiol, testosterone, and dihydrotestosterone. However, the enzyme has some reductive activity and can synthesize estradiol from estrone. The protein encoded by this gene is similar to Ke6 and is a member of the short-chain dehydrogenase superfamily. An alternatively spliced transcript of this gene has been detected, but the full-length nature of this variant has not been determined."<ref name=RefSeq7923>{{ cite web
|author=RefSeq
|title=HSD17B8 hydroxysteroid 17-beta dehydrogenase 8 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/7923
|accessdate=11 April 2020 }}</ref>
Gene ID: 8705 is B3GALT4 beta-1,3-galactosyltransferase 4 on 6p21.32: "his gene is a member of the beta-1,3-galactosyltransferase (beta3GalT) gene family. This family encodes type II membrane-bound glycoproteins with diverse enzymatic functions using different donor substrates (UDP-galactose and UDP-N-acetylglucosamine) and different acceptor sugars (N-acetylglucosamine, galactose, N-acetylgalactosamine). The beta3GalT genes are distantly related to the Drosophila Brainiac gene and have the protein coding sequence contained in a single exon. The beta3GalT proteins also contain conserved sequences not found in the beta4GalT or alpha3GalT proteins. The carbohydrate chains synthesized by these enzymes are designated as type 1, whereas beta4GalT enzymes synthesize type 2 carbohydrate chains. The ratio of type 1:type 2 chains changes during embryogenesis. By sequence similarity, the beta3GalT genes fall into at least two groups: beta3GalT4 and 4 other beta3GalT genes (beta3GalT1-3, beta3GalT5). This gene is oriented telomere to centromere in close proximity to the ribosomal protein S18 gene. The functionality of the encoded protein is limited to ganglioseries glycolipid biosynthesis."<ref name=RefSeq8705>{{ cite web
|author=RefSeq
|title=B3GALT4 beta-1,3-galactosyltransferase 4 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/8705
|accessdate=11 April 2020 }}</ref>
Gene ID: 8831 is SYNGAP1 synaptic Ras GTPase activating protein 1 on 6p21.32: "This gene encodes a Ras GTPase activating protein that is a member of the N-methyl-D-aspartate receptor complex. The N-terminal domain of the protein contains a Ras-GAP domain, a pleckstrin homology domain, and a C2 domain that may be involved in binding of calcium and phospholipids. The C-terminal domain consists of a ten histidine repeat region, serine and tyrosine phosphorylation sites, and a T/SXV motif required for postsynaptic scaffold protein interaction. The encoded protein negatively regulates Ras, Rap and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking to the postsynaptic membrane to regulate synaptic plasticity and neuronal homeostasis. Allelic variants of this gene are associated with intellectual disability and autism spectrum disorder. Alternative splicing results in multiple transcript variants."<ref name=RefSeq8831>{{ cite web
|author=RefSeq
|title=SYNGAP1 synaptic Ras GTPase activating protein 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=November 2016
|url=https://www.ncbi.nlm.nih.gov/gene/8831
|accessdate=11 April 2020 }}</ref>
# NP_001123538.1 ras/Rap GTPase-activating protein SynGAP isoform 2.<ref name=RefSeq8831/>
# NP_006763.2 ras/Rap GTPase-activating protein SynGAP isoform 1.<ref name=RefSeq8831/>
{{clear}}
===Class III===
===Class III===
{{main|MHC class III}}
{{main|MHC class III}}
{{main|Major histocompatibility complex class III gene family}}
MHC class III region encodes for other immune components, such as [[Complement system|complement]] components (e.g., [[Complement component 2|C2]], [[Complement component 4|C4]], [[Complement factor B|factor B]]) and some that encode [[cytokine]]s (e.g., [[TNF-α]]) and also [[Heat shock protein|HSP]]s. They are mainly known from their genes because their gene cluster is present between those of class I and class II.<ref name="gruen01">{{cite journal |last1=Gruen |first1=JR |last2=Weissman |first2=SM |title=Human MHC class III and IV genes and disease associations |journal=Frontiers in Bioscience |date=2001 |volume=6 |issue=3 |pages=D960-172 |pmid=11487469 |url=https://www.bioscience.org/2001/v6/d/gruen/fulltext.htm|doi=10.2741/A658 }}</ref> The gene cluster was discovered in between class I and class II genes on the short (p) arm of [[human chromosome 6]]. It was later found that it contains many genes for different signalling molecules such as [[tumour necrosis factors]] (TNFs) and [[heat shock proteins]]. More than 60 MHC class III genes are described, which is about 28% of the total MHC genes (224).<ref>{{cite journal |last1=The MHC sequencing consortium |title=Complete sequence and gene map of a human major histocompatibility complex |journal=Nature |date=1999 |volume=401 |issue=6756 |pages=921–923 |doi=10.1038/44853 |pmid=10553908|bibcode=1999Natur.401..921T }}</ref>
MHC class III genes are located on chromosome 6 (6p21.3) in humans. It covers 700 kb and contains 61 genes. The gene cluster is the most gene-dense region of the human genome. They are basically similar with those of other animals. The functions of many genes are yet unknown.<ref>{{cite journal |last1=Xie |first1=T |last2=Rowen |first2=L |last3=Aguado |first3=B |last4=Ahearn |first4=ME |last5=Madan |first5=A |last6=Qin |first6=S |last7=Campbell |first7=RD |last8=Hood |first8=L |title=Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse |journal=Genome Research |date=2003 |volume=13 |issue=12 |pages=2621–36 |doi=10.1101/gr.1736803 |pmid=14656967 |pmc=403804}}</ref> Many retroelements such as human endogenous retrovirus (HERV) and Alu elements are located in the cluster.<ref>{{cite journal |last1=Dawkins |first1=R |last2=Leelayuwat |first2=C |last3=Gaudieri |first3=S |last4=Tay |first4=G |last5=Hui |first5=J |last6=Cattley |first6=S |last7=Martinez |first7=P |last8=Kulski |first8=J |title=Genomics of the major histocompatibility complex: haplotypes, duplication, retroviruses and disease. |journal=Immunological Reviews |date=1999 |volume=167 |pages=275–304 |doi=10.1111/j.1600-065X.1999.tb01399.x |pmid=10319268}}</ref> The region containing genes ''G11/C4/Z/CYP21/X/Y'', varying in size from 142 to 214 kb, is known as the most complex gene cluster in the human genome.<ref>{{cite journal |last1=Milner |first1=CM |last2=Campbell |first2=RD |title=Genetic organization of the human MHC class III region. |journal=Frontiers in Bioscience |date=2001 |volume=6 |issue=3 |pages=D914-926 |pmid=11487476 |url=https://www.bioscience.org/2001/v6/d/milner/fulltext.htm|doi=10.2741/A653 }}</ref>
MHC class III genes are similar in humans, mouse, frog (''Xenopus tropicalis''), and gray short-tailed opossum, but not all genes are common. For example, human ''NCR3'', ''MIC'' and ''MCCD1'' are absent in mouse. Human ''NCR3'' and ''LST1'' are absent in opossum.<ref name="deakin"/> However, birds (chicken and quail) have only a single gene, which codes for a complement component gene (C4).<ref>{{cite journal |last1=Shiina |first1=T |last2=Shimizu |first2=S |last3=Hosomichi |first3=K |last4=Kohara |first4=S |last5=Watanabe |first5=S |last6=Hanzawa |first6=K |last7=Beck |first7=S |last8=Kulski |first8=JK |last9=Inoko |first9=H |title=Comparative genomic analysis of two avian (quail and chicken) MHC regions |journal=Journal of Immunology |date=2004 |volume=172 |issue=11 |pages=6751–63 |pmid=15153492 |url=http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=15153492|doi=10.4049/jimmunol.172.11.6751 }}</ref> In fishes, the genes are distributed in different chromosomes.<ref>{{cite journal |last1=Sambrook |first1=JG |last2=Figueroa |first2=F |last3=Beck |first3=S |title=A genome-wide survey of Major Histocompatibility Complex (MHC) genes and their paralogues in zebrafish |journal=BMC Genomics |date=2005 |volume=6 |pages=152 |doi=10.1186/1471-2164-6-152 |pmid=16271140 |pmc=1309616}}</ref>
Gene ID: 177 is [[RAGE (receptor)|AGER]] advanced glycosylation end-product specific receptor on 6p21.32: "The advanced glycosylation end product (AGE) receptor encoded by this gene is a member of the immunoglobulin superfamily of cell surface receptors. It is a multiligand receptor, and besides AGE, interacts with other molecules implicated in homeostasis, development, and inflammation, and certain diseases, such as diabetes and Alzheimer's disease. Many alternatively spliced transcript variants encoding different isoforms, as well as non-protein-coding variants, have been described for this gene (PMID:18089847)."<ref name=RefSeq177>{{ cite web
|author=RefSeq
|title=AGER advanced glycosylation end-product specific receptor [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=May 2011
|url=https://www.ncbi.nlm.nih.gov/gene/177
|accessdate=7 April 2020 }}</ref>
# NP_001127.1 advanced glycosylation end product-specific receptor isoform 1 precursor: "Transcript Variant: This variant (1, also known as RAGE) represents the predominant transcript, and encodes isoform 1."<ref name=RefSeq177/>
# NP_001193858.1 advanced glycosylation end product-specific receptor isoform 2 precursor: "Transcript Variant: This variant (2, also known as RAGE_v5) uses an alternate in-frame donor splice site at an internal coding exon compared to variant 1. This results in a longer isoform (2) containing an additional protein segment compared to isoform 1."<ref name=RefSeq177/>
# NP_001193861.1 advanced glycosylation end product-specific receptor isoform 3 precursor: "Transcript Variant: This variant (3, also known as RAGE_v4) uses alternate in-frame acceptor and donor splice sites at two internal coding exons compared to variant 1. This results in a shorter isoform (2) missing two internal protein segments compared to isoform 1."<ref name=RefSeq177/>
# NP_001193863.1 advanced glycosylation end product-specific receptor isoform 4 precursor: "Transcript Variant: This variant (4, also known as RAGE_v6) lacks the penultimate coding exon, and uses alternate donor splice sites at two internal coding exons compared to variant 1. This results in a frame-shift and a shorter isoform (4) with a distinct C-terminus compared to isoform 1."<ref name=RefSeq177/>
# NP_001193865.1 advanced glycosylation end product-specific receptor isoform 5 precursor: "Transcript Variant: This variant (5, also known as RAGE_v9) lacks the penultimate coding exon, and uses alternate acceptor and donor splice sites at two internal coding exons compared to variant 1. This results in a frame-shift and a shorter isoform (5) with a distinct C-terminus compared to isoform 1."<ref name=RefSeq177/>
# NP_001193869.1 advanced glycosylation end product-specific receptor isoform 6 precursor: "Transcript Variant: This variant (6, also known as RAGE_v1) lacks the penultimate coding exon, and uses an alternate donor splice site at another coding exon compared to variant 1. This results in a frame-shift and a shorter isoform (6, also known as esRAGE and soluble RAGE) with a distinct C-terminus compared to isoform 1. This isoform lacks the transmembrane and intracellular domains, is secreted (PMID:18089847), and thought to function as a decoy receptor that inhibits RAGE signaling, and thus prevent the pathological progression of some pathologic conditions, such as Alzheimer's disease (PMID:18431028). Variants 6 and 9 encode the same isoform."<ref name=RefSeq177/>
# NP_001193883.1 advanced glycosylation end product-specific receptor isoform 8 precursor: "Transcript Variant: This variant (8, also known as RAGE_v8) lacks two internal coding exons, and uses an alternate donor splice site at another coding exon compared to variant 1. This results in a frame-shift, and a shorter isoform (8) with a distinct C-terminus compared to isoform 1."<ref name=RefSeq177/>
# NP_001193895.1 advanced glycosylation end product-specific receptor isoform 6 precursor: "Transcript Variant: This variant (9, also known as RAGE_v10) lacks the penultimate coding exon, and uses alternate splice sites at other exons at the 3' end compared to variant 1. This results in a frame-shift and a shorter isoform (6, also known as esRAGE and soluble RAGE) with a distinct C-terminus compared to isoform 1. Variants 6 and 9 encode the same isoform."<ref name=RefSeq177/>
# NP_751947.1 advanced glycosylation end product-specific receptor isoform 7 precursor: "Transcript Variant: This variant (7, also known as RAGE_v16) uses alternate splice sites at several internal coding exons compared to variant 1. This results in a frame-shift and a shorter isoform (7, also known as hRAGEsec) with a distinct C-terminus compared to isoform 1."<ref name=RefSeq177/>
Gene ID: 578 is [[Bcl-2 homologous antagonist killer|BAK1]] BCL2 antagonist/killer 1 on 6p21.31: "The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress."<ref name=RefSeq578>{{ cite web
|author=RefSeq
|title=BAK1 BCL2 antagonist/killer 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/578
|accessdate=7 April 2020 }}</ref>
Gene ID: 629 is CFB [[Complement factor B|complement factor B]] on 6p21.33: "This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single chain polypeptide. Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. The active subunit Bb is a serine protease which associates with C3b to form the alternative pathway C3 convertase. Bb is involved in the proliferation of preactivated B lymphocytes, while Ba inhibits their proliferation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. This cluster includes several genes involved in regulation of the immune reaction. Polymorphisms in this gene are associated with a reduced risk of age-related macular degeneration. The polyadenylation site of this gene is 421 bp from the 5' end of the gene for complement component 2."<ref name=RefSeq629>{{ cite web
|author=RefSeq
|title=CFB complement factor B [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/629
|accessdate=6 April 2020 }}</ref>
# NP_001701.2 complement factor B preproprotein.<ref name=RefSeq629/>
Gene ID: 717 is [[Complement component 2|C2]] complement C2 on 6p21.33: "Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined."<ref name=RefSeq717>{{ cite web
|author=RefSeq
|title=C2 complement C2 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=March 2009
|url=https://www.ncbi.nlm.nih.gov/gene/717
|accessdate=6 April 2020 }}</ref>
# NP_000054.2 complement C2 isoform 1 preproprotein: "Transcript Variant: This variant (1) encodes the longest isoform (1)."<ref name=RefSeq717/>
# NP_001139375.1 complement C2 isoform 2 precursor: "Transcript Variant: This variant (2) lacks two in-frame exons in the 5' coding region, compared to variant 1, that results in an isoform (2) with a shorter N-terminus that lacks one of two SUSHI repeat domains, compared to isoform 1."<ref name=RefSeq717/>
# NP_001171534.1 complement C2 isoform 3: "Transcript Variant: This variant (3) has an alternate 5' sequence and lacks an in-frame internal segment, as compared to variant 1. The resulting isoform (3) is shorter; it has a distinct N-terminus and lacks an internal segment, as compared to isoform 1."<ref name=RefSeq717/>
# NP_001269386.1 complement C2 isoform 4: "Transcript Variant: This variant (4) represents use of an alternate promoter and has multiple differences in the coding region compared to variant 1. The resulting protein (isoform 4) has a distinct N-terminus and is shorter than isoform 1."<ref name=RefSeq717/>
# NP_001269387.1 complement C2 isoform 5: "Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (5) has a shorter and distinct N-terminus compared to isoform 1."<ref name=RefSeq717/>
# NP_001269388.1 complement C2 isoform 6 precursor: "Transcript Variant: This variant (6) uses an alternate 3' exon structure, and thus differs in the 3' coding region and 3' UTR compared to variant 1. It encodes isoform 6 which is shorter and has a distinct C-terminus, compared to isoform 1."<ref name=RefSeq717/>
Gene ID: 720 is [[C4A]] complement C4A (Rodgers blood group) aka MHC class III region complement on 6p21.33: "This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain is cleaved to release C4 anaphylatoxin, an antimicrobial peptide and a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus and type I diabetes mellitus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. Two transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq720>{{ cite web
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=November 2014
|url=https://www.ncbi.nlm.nih.gov/gene/720
|accessdate=6 April 2020 }}</ref>
# NP_001239133.1 complement C4-A isoform 2 preproprotein: "Transcript Variant: This variant (2) lacks an alternate in-frame segment compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1."<ref name=RefSeq720/>
# NP_009224.2 complement C4-A isoform 1 preproprotein: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."<ref name=RefSeq720/>
Gene ID: 721 is C4B [[Complement component 4B|complement C4B]] (Chido blood group) on 6p21.33: "This gene encodes the basic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. In addition, this gene exists as a long form and a short form due to the presence or absence of a 6.4 kb endogenous HERV-K retrovirus in intron 9."<ref name=RefSeq721>{{ cite web
Gene ID: 780 is [[DDR1]] discoidin domain receptor tyrosine kinase 1 on 6p21.33: "Receptor tyrosine kinases play a key role in the communication of cells with their microenvironment. These kinases are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene belongs to a subfamily of tyrosine kinase receptors with homology to Dictyostelium discoideum protein discoidin I in their extracellular domain, and that are activated by various types of collagen. Expression of this protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, it has been shown to be significantly overexpressed in several human tumors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene."<ref name=RefSeq780>{{ cite web
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=February 2011
|url=https://www.ncbi.nlm.nih.gov/gene/780
|accessdate=7 April 2020 }}</ref>
# NP_001189450.1 epithelial discoidin domain-containing receptor 1 isoform 4 precursor: "Transcript Variant: This variant (4) is missing an internal coding exon compared to variant 1. This results in a frame-shift, and early translation termination, rendering this transcript a candidate for nonsense-mediated mRNA decay (NMD). However, the encoded isoform (4, also known as DDR1d) is represented as it has been detected in vivo in several colon carcinoma cell lines (PMID:11344127). This isoform is truncated and lacks the catalytic tyrosine kinase domain, therefore, most likely lacks intrinsic tyrosine kinase activity. It may function in some other regulatory capacity."<ref name=RefSeq780/>
# NP_001189451.1 epithelial discoidin domain-containing receptor 1 isoform 5 precursor: "Transcript Variant: This variant (5) is missing an internal coding exon, and uses an alternate acceptor splice site at one of the coding exons compared to variant 1. This results in localized frame-shift, and a shorter isoform (5, also known as DDR1e) compared to isoform 1. This isoform lacks the ATP binding site, therefore, most likely lacks intrinsic tyrosine kinase activity. It may function in some other regulatory capacity."<ref name=RefSeq780/>
# NP_001189452.1 epithelial discoidin domain-containing receptor 1 isoform 6 precursor: "Transcript Variant: This variant (6) contains an alternate 5' terminal exon compared to variant 1. This results in translation initiation from an in-frame upstream start codon, and a longer isoform (6) with a distinct N-terminus compared to isoform 1."<ref name=RefSeq780/>
# NP_001284581.1 epithelial discoidin domain-containing receptor 1 isoform 1 precursor: "Transcript Variant: This variant (7) differs in the 5' UTR compared to variant 1. It encodes isoform 1 (also known as DDR1a). Variants 1, 7, and 8 encode the same isoform (1)."<ref name=RefSeq780/>
# NP_001284582.1 epithelial discoidin domain-containing receptor 1 isoform 1 precursor: "Transcript Variant: This variant (8) differs in the 5' UTR compared to variant 1. It encodes isoform 1 (also known as DDR1a). Variants 1, 7, and 8 encode the same isoform (1)."<ref name=RefSeq780/>
# NP_001284583.1 epithelial discoidin domain-containing receptor 1 isoform 2 precursor: "Transcript Variant: This variant (9) contains an additional in-frame coding exon and differs in the 5' UTR compared to variant 1, resulting in a longer isoform (2, also known as DDR1b) with a 37 aa protein segment not found in isoform 1. Variants 2 and 9 encode the same isoform (2)."<ref name=RefSeq780/>
# NP_001945.3 epithelial discoidin domain-containing receptor 1 isoform 1 precursor: "Transcript Variant: This variant (1) represents the predominant transcript, and encodes isoform 1 (also known as DDR1a). Variants 1, 7, and 8 encode the same isoform (1)."<ref name=RefSeq780/>
# NP_054699.2 epithelial discoidin domain-containing receptor 1 isoform 2 precursor: "Transcript Variant: This variant (2) contains an additional in-frame coding exon compared to variant 1, resulting in a longer isoform (2, also known as DDR1b) with a 37 aa protein segment not found in isoform 1. Variants 2 and 9 encode the same isoform (2)."<ref name=RefSeq780/>
# NP_054700.2 epithelial discoidin domain-containing receptor 1 isoform 3 precursor: "Transcript Variant: This variant (3) contains an additional in-frame coding exon, and uses an alternate in-frame acceptor splice site at one of the coding exons compared to variant 1. This results in the longest isoform (3, also known as DDR1c) with additional protein segments not found in isoform 1."<ref name=RefSeq780/>
Gene ID: 1041 is CDSN [[corneodesmosin]] on 6p21.33: "This gene encodes a protein found in corneodesmosomes, which localize to human epidermis and other cornified squamous epithelia. The encoded protein undergoes a series of cleavages during corneocyte maturation. This gene is highly polymorphic in human populations, and variation has been associated with skin diseases such as psoriasis, hypotrichosis and peeling skin syndrome. The gene is located in the major histocompatibility complex (MHC) class I region on chromosome 6."<ref name=RefSeq1041>{{ cite web
|author=RefSeq
|title=CDSN corneodesmosin [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
Gene ID: 1192 is CLIC1 chloride intracellular channel 1 on 6p21.33: "Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. Chloride intracellular channel 1 is a member of the p64 family; the protein localizes principally to the cell nucleus and exhibits both nuclear and plasma membrane chloride ion channel activity."<ref name=RefSeq1192>{{ cite web
|author=RefSeq
|title=CLIC1 chloride intracellular channel 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/1192
|accessdate=10 April 2020 }}</ref>
# NP_001274522.1 chloride intracellular channel protein 1: "Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2 and 3 encode the same protein."<ref name=RefSeq1192/>
# NP_001274523.1 chloride intracellular channel protein 1: "Transcript Variant: This variant (3) has an alternate exon in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein."<ref name=RefSeq1192/>
# NP_001279.2 chloride intracellular channel protein 1: "Transcript Variant: This variant (2) has an alternate exon in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein."<ref name=RefSeq1192/>
Gene ID: 1432 is [[MAPK14]] mitogen-activated protein kinase 14 on 6p21.31: "The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported."<ref name=RefSeq1432>{{ cite web
|author=RefSeq
|title=MAPK14 mitogen-activated protein kinase 14 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/1432
|accessdate=6 April 2020 }}</ref>
# NP_001306.1 mitogen-activated protein kinase 14 isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1) [...] STKc_p38alpha; Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14)."<ref name=RefSeq1432/>
# NP_620581.1 mitogen-activated protein kinase 14 isoform 2: "Transcript Variant: This variant (2) contains a different segment within the coding region when compared to variant 1. The translation frame remains the same, and the resulting isoform 2 has an internal segment different from that of isoform 1."<ref name=RefSeq1432/>
# NP_620582.1 mitogen-activated protein kinase 14 isoform 3: "Transcript Variant: This variant (3) contains a different internal segment within the coding region, and a different 3' coding region as well as a different 3' UTR, when compared to variant 1. It thus encodes an isoform that has a different internal segment, and a distinct C-terminus, as compared to isoform 1."<ref name=RefSeq1432/>
# NP_620583.1 mitogen-activated protein kinase 14 isoform 4: "Transcript Variant: This variant (4) contains a different internal segment when compared to variant 1. It thus encodes an isoform that has a different and shorter internal segment, as compared to isoform 1."<ref name=RefSeq1432/>
Gene ID: 1460 is [[CSNK2B]] casein kinase 2 beta on 6p21.33: "This gene encodes the beta subunit of casein kinase II, a ubiquitous protein kinase which regulates metabolic pathways, signal transduction, transcription, translation, and replication. The enzyme is composed of three subunits, alpha, alpha prime and beta, which form a tetrameric holoenzyme. The alpha and alpha prime subunits are catalytic, while the beta subunit serves regulatory functions. The enzyme localizes to the endoplasmic reticulum and the Golgi apparatus. Two transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq1460>{{ cite web
|author=RefSeq
|title=CSNK2B casein kinase 2 beta [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=September 2013
|url=https://www.ncbi.nlm.nih.gov/gene/1460
|accessdate=8 April 2020 }}</ref>
# NP_001269314.1 casein kinase II subunit beta isoform 2: "Transcript Variant: This variant (2) uses an alternate in-frame splice junction in the 3' coding sequence compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1."<ref name=RefSeq1460/>
# NP_001311.3 casein kinase II subunit beta isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."<ref name=RefSeq1460/>
Gene ID: 1589 is [[21-Hydroxylase|CYP21A2]] cytochrome P450 family 21 subfamily A member 2 on 6p21.33: "This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone. Mutations in this gene cause congenital adrenal hyperplasia. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought to account for many cases of steroid 21-hydroxylase deficiency. Two transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq1589>{{ cite web
|author=RefSeq
|title=CYP21A2 cytochrome P450 family 21 subfamily A member 2 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/1589
|accessdate=6 April 2020 }}</ref>
# NP_000491.4 steroid 21-hydroxylase isoform a: "Transcript Variant: This variant (1) encodes the longer isoform (a)."<ref name=RefSeq1589/>
# NP_001122062.3 steroid 21-hydroxylase isoform b: "Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a."<ref name=RefSeq1589/>
# NP_001355072.1 steroid 21-hydroxylase isoform c: "Transcript Variant: This variant (3), as well as variant 4, encodes isoform c."<ref name=RefSeq1589/>
# NP_001355073.1 steroid 21-hydroxylase isoform c: "Transcript Variant: This variant (4), as well as variant 3, encodes isoform c."<ref name=RefSeq1589/>
Gene ID: 1797 is DXO decapping exoribonuclease aka [[DOM3Z]] on 6p21.33: "This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. The function of its protein product is unknown, but its ubiquitous expression and conservation in both simple and complex eukaryotes suggests that this may be a housekeeping gene."<ref name=RefSeq1797>{{ cite web
|author=RefSeq
|title=DXO decapping exoribonuclease [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/1797
|accessdate=8 April 2020 }}</ref>
# NP_001358134.1 decapping and exoribonuclease protein isoform 1: "Transcript Variant: This variant (1) represents the longest transcript. Both variants 1 and 3 encode the same protein."<ref name=RefSeq1797/>
# NP_001358135.1 decapping and exoribonuclease protein isoform 1: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 3 encode the same protein."<ref name=RefSeq1797/>
# NP_005501.2 decapping and exoribonuclease protein isoform 2.<ref name=RefSeq1797/>
Gene ID: 2289 is [[FKBP5]] FKBP prolyl isomerase 5 on 6p21.31: "The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It is thought to mediate calcineurin inhibition. It also interacts functionally with mature hetero-oligomeric progesterone receptor complexes along with the 90 kDa heat shock protein and P23 protein. This gene has been found to have multiple polyadenylation sites. Alternative splicing results in multiple transcript variants."<ref name=RefSeq2289>{{ cite web
|author=RefSeq
|title=FKBP5 FKBP prolyl isomerase 5 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=March 2009
|url=https://www.ncbi.nlm.nih.gov/gene/2289
|accessdate=8 April 2020 }}</ref>
# NP_001139247.1 peptidyl-prolyl cis-trans isomerase FKBP5 isoform 1: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same isoform (1)."<ref name=RefSeq2289/>
# NP_001139248.1 peptidyl-prolyl cis-trans isomerase FKBP5 isoform 1: "Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same isoform (1)."<ref name=RefSeq2289/>
# NP_001139249.1 peptidyl-prolyl cis-trans isomerase FKBP5 isoform 2: "Transcript Variant: This variant (4) has multiple differences in the coding region and 3' UTR compared to variant 1 which result in a frameshift. The resulting protein (isoform 2) is shorter and has a distinct C-terminus compared to isoform 1."<ref name=RefSeq2289/>
# NP_004108.1 peptidyl-prolyl cis-trans isomerase FKBP5 isoform 1: "Transcript Variant: This variant (1) represents the shortest transcript and encodes the longer isoform (1). Variants 1, 2 and 3 encode the same isoform (1)."<ref name=RefSeq2289/>
Gene ID: 2914 is [[Metabotropic glutamate receptor 4|GRM4]] glutamate metabotropic receptor 4 on 6p21.31: "L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Several transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq2914>{{ cite web
|author=RefSeq
|title=GRM4 glutamate metabotropic receptor 4 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=February 2012
|url=https://www.ncbi.nlm.nih.gov/gene/2914
|accessdate=8 April 2020 }}</ref>
# NP_000832.1 metabotropic glutamate receptor 4 isoform 1 precursor: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."<ref name=RefSeq2914/>
# NP_001243738.1 metabotropic glutamate receptor 4 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence, and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus and lacks an alternate internal segment compared to isoform 1."<ref name=RefSeq2914/>
# NP_001243740.1 metabotropic glutamate receptor 4 isoform 4 precursor: "Transcript Variant: This variant (4) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1."<ref name=RefSeq2914/>
# NP_001243741.1 metabotropic glutamate receptor 4 isoform 5: "Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (5) has a shorter and distinct N-terminus compared to isoform 1."<ref name=RefSeq2914/>
# NP_001243742.1 metabotropic glutamate receptor 4 isoform 6: "Transcript Variant: This variant (6) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (6) has a shorter and distinct N-terminus compared to isoform 1."<ref name=RefSeq2914/>
# NP_001269776.1 metabotropic glutamate receptor 4 isoform 8: "Transcript Variant: This variant (8) uses an alternate 5' structure and thus differs in the 5' UTR and 5' coding region compared to variant 1. These differences cause translation initiation at a downstream AUG and result in an isoform (8) with a shorter N-terminus, compared to isoform 1."<ref name=RefSeq2914/>
Gene ID: 4295 is MLN motilin on 6p21.31: "This gene encodes a small peptide hormone that is secreted by cells of the small intestine to regulate gastrointestinal contractions and motility. Proteolytic processing of the secreted protein produces the mature peptide and a byproduct referred to as motilin-associated peptide (MAP). Three transcript variants encoding different preproprotein isoforms but the same mature peptide have been found for this gene."<ref name=RefSeq4295>{{ cite web
|author=RefSeq
|title=MLN motilin [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=May 2010
|url=https://www.ncbi.nlm.nih.gov/gene/4295
|accessdate=9 April 2020 }}</ref>
# NP_001035198.1 promotilin isoform 2 preproprotein: "Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a shorter preproprotein (isoform 2) but not affecting the mature peptide."<ref name=RefSeq4295/>
# NP_001171627.1 promotilin isoform 3 preproprotein: "Transcript Variant: This variant (3) uses an alternate in-frame splice junction at the 3' end of an exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1."<ref name=RefSeq4295/>
# NP_002409.1 promotilin isoform 1 preproprotein: "ranscript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."<ref name=RefSeq4295/>
Gene ID: 4439 is MSH5 mutS homolog 5 on 6p21.33: "This gene encodes a member of the mutS family of proteins that are involved in DNA mismatch repair and meiotic recombination. This protein is similar to a Saccharomyces cerevisiae protein that participates in segregation fidelity and crossing-over events during meiosis. This protein plays a role in promoting ionizing radiation-induced apoptosis. This protein forms hetero-oligomers with another member of this family, mutS homolog 4. Polymorphisms in this gene have been linked to various human diseases, including IgA deficiency, common variable immunodeficiency, and premature ovarian failure. Alternative splicing results multiple transcript variants. Read-through transcription also exists between this gene and the downstream chromosome 6 open reading frame 26 (C6orf26) gene."<ref name=RefSeq4439>{{ cite web
|author=RefSeq
|title=MSH5 mutS homolog 5 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=February 2011
|url=https://www.ncbi.nlm.nih.gov/gene/2623
|accessdate=9 April 2020 }}</ref>
# NP_002432.1 mutS protein homolog 5 isoform c: "Transcript Variant: This variant (3) differs in the 5' UTR and uses alternate in-frame splice sites in both the central and 3' coding regions, compared to variant 1, resulting in an isoform (c) that is longer than isoform a. Both variants 3 and 4 encode the same isoform."<ref name=RefSeq4439/>
# NP_079535.4 mutS protein homolog 5 isoform a: "Transcript Variant: This variant (1) represents the shortest transcript and encodes the shortest isoform (a)."<ref name=RefSeq4439/>
# NP_751897.1 mutS protein homolog 5 isoform b: "Transcript Variant: This variant (2) uses alternate in-frame splice sites in both the central and 3' coding regions, compared to variant 1, resulting in an isoform (b) that is longer than isoform a."<ref name=RefSeq4439/>
# NP_751898.1 mutS protein homolog 5 isoform c: "Transcript Variant: This variant (4) uses alternate in-frame splice sites in both the central and 3' coding regions, compared to variant 1, resulting in an isoform (c) that is longer than isoform a. Both variants 3 and 4 encode the same isoform."<ref name=RefSeq4439/>
Gene ID: 4736 is RPL10A ribosomal protein L10a on 6p21.31: "Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L1P family of ribosomal proteins. It is located in the cytoplasm. The expression of this gene is downregulated in the thymus by cyclosporin-A (CsA), an immunosuppressive drug. Studies in mice have shown that the expression of the ribosomal protein L10a gene is downregulated in neural precursor cells during development. This gene previously was referred to as NEDD6 (neural precursor cell expressed, developmentally downregulated 6), but it has been renamed RPL10A (ribosomal protein 10a). As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome."<ref name=RefSeq4736>{{ cite web
|author=RefSeq
|title=RPL10A ribosomal protein L10a [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/4736
|accessdate=9 April 2020 }}</ref>
Gene ID: 4758 is NEU1 neuraminidase 1 on 6p21.33: "The protein encoded by this gene is a lysosomal enzyme that cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter is also referred to as 'protective protein'). Mutations in this gene can lead to sialidosis, a lysosomal storage disease that can be type 1 (cherry red spot-myoclonus syndrome or normosomatic type), which is late-onset, or type 2 (the dysmorphic type), which occurs at an earlier age with increased severity."<ref name=RefSeq4758>{{ cite web
|author=RefSeq
|title=NEU1 neuraminidase 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
Gene ID: 4795 is NFKBIL1 NFKB inhibitor like 1 on 6p21.33: "This gene encodes a divergent member of the I-kappa-B family of proteins. Its function has not been determined. The gene lies within the major histocompatibility complex (MHC) class I region on chromosome 6. Multiple transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq4795>{{ cite web
|author=RefSeq
|title=NFKBIL1 NFKB inhibitor like 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=January 2009
|url=https://www.ncbi.nlm.nih.gov/gene/4795
|accessdate=9 April 2020 }}</ref>
# NP_001138433.1 NF-kappa-B inhibitor-like protein 1 isoform 2: "Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the 3' end of an exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1."<ref name=RefSeq4795/>
# NP_001138434.1 NF-kappa-B inhibitor-like protein 1 isoform 3: "Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1."<ref name=RefSeq4795/>
# NP_001138435.1 NF-kappa-B inhibitor-like protein 1 isoform 4: "Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence and uses an alternate in-frame splice junction at the 3' end of an exon compared to variant 1. The resulting isoform (4) is shorter at the N-terminus and lacks an alternate internal segment compared to isoform 1."<ref name=RefSeq4795/>
# NP_004998.3 NF-kappa-B inhibitor-like protein 1 isoform 1: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."<ref name=RefSeq4795/>
Gene ID: 4855 is [[Neurogenic locus notch homolog protein 4|NOTCH4]] notch receptor 4 on 6p21.32: "This gene encodes a member of the NOTCH family of proteins. Members of this Type I transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple different domain types. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor may play a role in vascular, renal and hepatic development. Mutations in this gene may be associated with schizophrenia. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed."<ref name=RefSeq4855>{{ cite web
|author=RefSeq
|title=NOTCH4 notch receptor 4 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=January 2016
|url=https://www.ncbi.nlm.nih.gov/gene/4855
|accessdate=6 April 2020 }}</ref>
# NP_004548.3 neurogenic locus notch homolog protein 4 preproprotein: "Transcript Variant: This variant (1) represents the longest transcript and encodes the protein."<ref name=RefSeq4855/>
Gene ID: 5460 is POU5F1 POU class 5 homeobox 1 on 6p21.33: "This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12."<ref name=RefSeq5460>{{ cite web
|author=RefSeq
|title=POU5F1 POU class 5 homeobox 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=October 2013
|url=https://www.ncbi.nlm.nih.gov/gene/5460
|accessdate=9 April 2020 }}</ref>
# NP_001167002.1 POU domain, class 5, transcription factor 1 isoform 2: "Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame non-AUG (CUG) start codon, compared to variant 1. The resulting isoform (2, also known as OCT4B-190) is shorter at the N-terminus, compared to isoform 1. Variants 2 and 3 encode the same isoform (2). This variant may encode an additional isoform through the use of an alternative downstream AUG start codon. Use of alternate start codons and the non-AUG start codon is described in PMID:19489092."<ref name=RefSeq5460/>
# NP_001272915.1 POU domain, class 5, transcription factor 1 isoform 4: "Transcript Variant: This variant (4, also known as OCT4B1) contains multiple differences in the 5' UTR and the 5' coding region, compared to variant 1, and initiates translation at a downstream in-frame AUG start codon. The resulting isoform (4, also known as OCT4B-164) is shorter at the N-terminus, compared to isoform 1."<ref name=RefSeq5460/>
# NP_001272916.1 POU domain, class 5, transcription factor 1 isoform 3: "Transcript Variant: This variant (5, also known as OCT4B) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate AUG start codon, compared to variant 1. The resulting isoform (3, also known as OCT4B-265) is shorter and has a distinct N-terminus, compared to isoform 1. This variant represents an allele of variant 2 that contains an AUG start codon that is polymorphic in human populations (see rs3130932). This variant may encode additional isoforms through the use of alternative downstream AUG and non-AUG start codons, as described in PMID:19489092."<ref name=RefSeq5460/>
# NP_002692.2 POU domain, class 5, transcription factor 1 isoform 1: "Transcript Variant: This variant (1, also known as OCT4A) represents the shortest transcript and encodes the longest isoform (1)."<ref name=RefSeq5460/>
# NP_976034.4 POU domain, class 5, transcription factor 1 isoform 2: "Transcript Variant: This variant (2, also known as OCT4B) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame non-AUG (CUG) start codon, compared to variant 1. The resulting isoform (2, also known as OCT4B-190) is shorter at the N-terminus, compared to isoform 1. Variants 2 and 3 encode the same isoform (2). This variant may encode additional isoforms through the use of an alternative downstream AUG start codon, as well as an alternative upstream AUG start codon, which is polymorphic in human populations (AGG allele represented in this RefSeq; see rs3130932). Use of alternate start codons and the non-AUG start codon is described in PMID:19489092."<ref name=RefSeq5460/>
Gene ID: 5514 is PPP1R10 protein phosphatase 1 regulatory subunit 10 aka MHC class I region proline-rich protein CAT53 on 6p21.33: "This gene encodes a protein phosphatase 1 binding protein. The encoded protein plays a role in many cellular processes including cell cycle progression, DNA repair and apoptosis by regulating the activity of protein phosphatase 1. This gene lies within the major histocompatibility complex class I region on chromosome 6, and alternatively spliced transcript variants have been observed for this gene."<ref name=RefSeq5514>{{ cite web
|author=RefSeq
|title=PPP1R10 protein phosphatase 1 regulatory subunit 10 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2012
|url=https://www.ncbi.nlm.nih.gov/gene/5514
|accessdate=9 April 2020 }}</ref>
# NP_001363124.1 serine/threonine-protein phosphatase 1 regulatory subunit 10: "Transcript Variant: This variant (3) represents the longest transcript. Variants 1 and 3 both encode the same protein."<ref name=RefSeq5514/>
Gene ID: 5603 is MAPK13 mitogen-activated protein kinase 13 on 6p21.31: "This gene encodes a member of the mitogen-activated protein (MAP) kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The encoded protein is a p38 MAP kinase and is activated by proinflammatory cytokines and cellular stress. Substrates of the encoded protein include the transcription factor ATF2 and the microtubule dynamics regulator stathmin. Alternatively spliced transcript variants have been observed for this gene."<ref name=RefSeq5603>{{ cite web
|author=RefSeq
|title=MAPK13 mitogen-activated protein kinase 13 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2012
|url=https://www.ncbi.nlm.nih.gov/gene/5603
|accessdate=9 April 2020 }}</ref>
# NP_002745.1 mitogen-activated protein kinase 13: "Transcript Variant: This variant (1) represents the longer transcript and is protein-coding."<ref name=RefSeq5603/>
Gene ID: 6204 is RPS10 ribosomal protein S10 on 6p21.31: "Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S10E family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternate splicing results in multiple transcript variants that encode the same protein. Naturally occurring read-through transcription occurs between this locus and the neighboring locus NUDT3 (nudix (nucleoside diphosphate linked moiety X)-type motif 3)."<ref name=RefSeq6204>{{ cite web
|author=RefSeq
|title=RPS10 ribosomal protein S10 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=February 2011
|url=https://www.ncbi.nlm.nih.gov/gene/6204
|accessdate=10 April 2020 }}</ref>
# NP_001005.1 40S ribosomal protein S10: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein."<ref name=RefSeq6204/>
# NP_001190174.1 40S ribosomal protein S10: "Transcript Variant: This variant (1) represents the longer transcript. Variants 1, 2 and 3 encode the same protein."<ref name=RefSeq6204/>
# NP_001191020.1 40S ribosomal protein S10: "Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein."<ref name=RefSeq6204/>
Gene ID: 6631 is SNRPC small nuclear ribonucleoprotein polypeptide C on 6p21.31: "This gene encodes one of the specific protein components of the U1 small nuclear ribonucleoprotein (snRNP) particle required for the formation of the spliceosome. The encoded protein participates in the processing of nuclear precursor messenger RNA splicing. snRNP particles are attacked by autoantibodies frequently produced by patients with connective tissue diseases. The genome contains several pseudogenes of this functional gene. Alternative splicing results in a non-coding transcript variant."<ref name=RefSeq6631>{{ cite web
|author=RefSeq
|title=SNRPC small nuclear ribonucleoprotein polypeptide C [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=October 2009
|url=https://www.ncbi.nlm.nih.gov/gene/6631
|accessdate=10 April 2020 }}</ref>
# NP_003084.1 U1 small nuclear ribonucleoprotein C: "Transcript Variant: This variant (1) represents the longer transcript."<ref name=RefSeq6631/>
Gene ID: 6732 is SRPK1 SRSF protein kinase 1 on 6p21.31: "This gene encodes a serine/arginine protein kinase specific for the SR (serine/arginine-rich domain) family of splicing factors. The protein localizes to the nucleus and the cytoplasm. It is thought to play a role in regulation of both constitutive and alternative splicing by regulating intracellular localization of splicing factors. Alternative splicing of this gene results in multiple transcript variants. Additional alternatively spliced transcript variants have been described for this gene, but their full length nature have not been determined."<ref name=RefSeq6732>{{ cite web
|author=RefSeq
|title=SRPK1 SRSF protein kinase 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2010
|url=https://www.ncbi.nlm.nih.gov/gene/6732
|accessdate=10 April 2020 }}</ref>
# NP_003128.3 SRSF protein kinase 1: "Transcript Variant: This variant (1) represents the shorter transcript."<ref name=RefSeq6732/>
Gene ID: 6882 is TAF11 TATA-box binding protein associated factor 11 on 6p21.31: "Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes a small subunit of TFIID that is present in all TFIID complexes and interacts with TBP. This subunit also interacts with another small subunit, TAF13, to form a heterodimer with a structure similar to the histone core structure. Two transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq6882>{{ cite web
|author=RefSeq
|title=TAF11 TATA-box binding protein associated factor 11 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2012
|url=https://www.ncbi.nlm.nih.gov/gene/6882
|accessdate=10 April 2020 }}</ref>
# NP_001257417.1 transcription initiation factor TFIID subunit 11 isoform 2: "Transcript Variant: This variant (2) lacks an alternate coding exon compared to variant 1, that causes a frameshift. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1."<ref name=RefSeq6882/>
# NP_005634.1 transcription initiation factor TFIID subunit 11 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."<ref name=RefSeq6882/>
Gene ID: 6941 is TCF19 transcription factor 19 on 6p21.33: "This gene encodes a protein that contains a PHD-type zinc finger domain and likely functions as a transcription factor. The encoded protein plays a role proliferation and apoptosis of pancreatic beta cells. Alternative splicing results in multiple transcript variants."<ref name=RefSeq6941>{{ cite web
|author=RefSeq
|title=TCF19 transcription factor 19 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=January 2016
|url=https://www.ncbi.nlm.nih.gov/gene/6941
|accessdate=10 April 2020 }}</ref>
# NP_001070979.1 transcription factor 19: "Transcript Variant: This variant (2) uses an alternate splice site in the 5' UTR compared to variant 1. Variants 1, 2, and 3 encode the same protein."<ref name=RefSeq6941/>
# NP_001305837.1 transcription factor 19: "Transcript Variant: This variant (3) lacks an alternate segment in the 5' UTR compared to variant 1. Variants 1, 2, and 3 encode the same protein."<ref name=RefSeq6941/>
# NP_009040.2 transcription factor 19: "Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2, and 3 encode the same protein."<ref name=RefSeq6941/>
Gene ID: 6954 is TCP11 t-complex 11 on 6p21.31.<ref name=RefSeq6954>{{ cite web
|author=RefSeq
|title=TCP11 t-complex 11 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=13 March 2020
|url=https://www.ncbi.nlm.nih.gov/gene/6954
|accessdate=10 April 2020 }}</ref>
# NP_001248746.2 T-complex protein 11 homolog isoform 3: "Transcript Variant: This variant (3) uses an alternate splice site in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (3) is shorter than isoform 1."<ref name=RefSeq6954/>
# NP_001248747.1 T-complex protein 11 homolog isoform 4: "Transcript Variant: This variant (4) lacks an exon in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (4) is shorter than isoform 1."<ref name=RefSeq6954/>
# NP_001248748.1 T-complex protein 11 homolog isoform 5: "Transcript Variant: This variant (5) lacks an exon and uses an alternate splice site in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (5) is shorter than isoform 1."<ref name=RefSeq6954/>
# NP_001248749.1 T-complex protein 11 homolog isoform 6: "Transcript Variant: This variant (6) differs in the 5' UTR, includes an alternate internal exon in the 5' region and initiates translation at a downstream, in-frame start codon, compared to variant 1. Variants 6 and 7 encode the same isoform (6), which has a shorter N-terminus compared to isoform 1."<ref name=RefSeq6954/>
# NP_001248750.1 T-complex protein 11 homolog isoform 6: "Transcript Variant: This variant (7) has multiple differences, including the use of a downstream, in-frame start codon, compared to variant 1. Variants 6 and 7 encode the same isoform (6), which has a shorter N-terminus compared to isoform 1."<ref name=RefSeq6954/>
# NP_001357616.1 T-complex protein 11 homolog isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1)."<ref name=RefSeq6954/>
# NP_061149.1 T-complex protein 11 homolog isoform 2: "Transcript Variant: This variant (2) has multiple differences, including the use of an alternate start codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct N-terminus, compared to isoform 1."<ref name=RefSeq6954/>
Gene ID: 7148 is TNXB [[Tenascin X|tenascin XB]] on 6p21.33-p21.32: "This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The tenascins have anti-adhesive effects, as opposed to fibronectin which is adhesive. This protein is thought to function in matrix maturation during wound healing, and its deficiency has been associated with the connective tissue disorder Ehlers-Danlos syndrome. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. It is one of four genes in this cluster which have been duplicated. The duplicated copy of this gene is incomplete and is a pseudogene which is transcribed but does not encode a protein. The structure of this gene is unusual in that it overlaps the CREBL1 and CYP21A2 genes at its 5' and 3' ends, respectively. Multiple transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq7148>{{ cite web
|author=RefSeq
|title=TNXB tenascin XB [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/7148
|accessdate=6 April 2020 }}</ref>
# NP_001352205.1 tenascin-X isoform 3 precursor: "Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (3). It should be noted that the exon combination of this variant lacks full-length transcript support in human; it is predicted based on a combination of partial human and homologous transcript alignments."<ref name=RefSeq7148/>
# NP_061978.6 tenascin-X isoform 1 precursor: "Transcript Variant: This variant (XB) uses an alternate in-frame splice junction compared to variant 3. The resulting isoform (1) has the same N- and C-termini but is shorter compared to isoform 3. It should be noted that the exon combination of this variant lacks full-length transcript support in human; it is predicted based on a combination of partial human and homologous transcript alignments."<ref name=RefSeq7148/>
# NP_115859.2 tenascin-X isoform 2: "Transcript Variant: This variant (XB-S) is transcribed from a cryptic internal promoter sequence and is substantially shorter than variant 3 at the 5' end. It encodes isoform 2, which is identical to the C-terminus of the full-length protein, isoform 3."<ref name=RefSeq7148/>
Gene ID: 7287 is TULP1 TUB like protein 1 on 6p21.31: "This gene encodes a member of the tubby-like gene family (TULPs). Members of this family have been identified in plants, vertebrates, and invertebrates. TULP proteins share a conserved C-terminal region of approximately 200 amino acid residues. The protein encoded by this gene is thought to play a role in the physiology of photoreceptors. Mutations in this gene are associated with recessive juvenile retinitis pigmentosa and Leber congenital amaurosis-15."<ref name=RefSeq7287>{{ cite web
|author=RefSeq
|title=TULP1 TUB like protein 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=November 2016
|url=https://www.ncbi.nlm.nih.gov/gene/7287
|accessdate=10 April 2020 }}</ref>
# NP_001276324.1 tubby-related protein 1 isoform 2: "Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. It encodes isoform 2, which lacks an internal segment and is shorter than isoform 1."<ref name=RefSeq7287/>
# NP_003313.3 tubby-related protein 1 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."<ref name=RefSeq7287/>
Gene ID: 7407 is VARS1 valyl-tRNA synthetase 1 on 6p21.33: "Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. The protein encoded by this gene belongs to class-I aminoacyl-tRNA synthetase family and is located in the class III region of the major histocompatibility complex."<ref name=RefSeq7407>{{ cite web
|author=RefSeq
|title=VARS1 valyl-tRNA synthetase 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/7407
|accessdate=10 April 2020 }}</ref>
Gene ID: 7629 is ZNF76 zinc finger protein 76 on 6p21.31.<ref name=RefSeq7629>{{ cite web
|author=RefSeq
|title=ZNF76 zinc finger protein 76 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=13 March 2020
|url=https://www.ncbi.nlm.nih.gov/gene/7629
|accessdate=10 April 2020 }}</ref>
# NP_001278961.1 zinc finger protein 76 isoform 2: "Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1."<ref name=RefSeq7629/>
# NP_003418.2 zinc finger protein 76 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."<ref name=RefSeq7629/>
Gene ID: 7936 is [[RDBP|NELFE]] negative elongation factor complex member E aka major histocompatibility complex gene RD on 6p21.33: "The protein encoded by this gene is part of a complex termed negative elongation factor (NELF) which represses RNA polymerase II transcript elongation. This protein bears similarity to nuclear RNA-binding proteins; however, it has not been demonstrated that this protein binds RNA. The protein contains a tract of alternating basic and acidic residues, largely arginine (R) and aspartic acid (D). The gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6."<ref name=RefSeq7936>{{ cite web
|author=RefSeq
|title=NELFE negative elongation factor complex member E [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
Gene ID: 7940 is LST1 leukocyte specific transcript 1 on 6p21.33: "The protein encoded by this gene is a membrane protein that can inhibit the proliferation of lymphocytes. Expression of this gene is enhanced by lipopolysaccharide, interferon-gamma, and bacteria. Several transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq7940>{{ cite web
|author=RefSeq
|title=LST1 leukocyte specific transcript 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=October 2011
|url=https://www.ncbi.nlm.nih.gov/gene/7940
|accessdate=11 April 2020 }}</ref>
# NP_001160010.1 leukocyte-specific transcript 1 protein isoform 6: "Transcript Variant: This variant (6) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1, resulting in an isoform (6) that is shorter than isoform 1. The 5' UTR of this variant is incomplete because the transcripts supporting this CDS exon combination lack a complete 5' UTR, and alternative splicing choices exist further upstream."<ref name=RefSeq7940/>
# NP_009092.3 leukocyte-specific transcript 1 protein isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1). The 5' UTR of this variant is incomplete because the transcripts supporting this CDS exon combination lack a complete 5' UTR, and alternative splicing choices exist further upstream."<ref name=RefSeq7940/>
# NP_995309.2 leukocyte-specific transcript 1 protein isoform 2: "Transcript Variant: This variant (2) includes an additional exon in the 5' UTR and lacks an internal exon that causes a frameshift in the 3' coding region, compared to variant 1. The encoded isoform (2) has a distinct C-terminus and is shorter than isoform 1."<ref name=RefSeq7940/>
# NP_995310.2 leukocyte-specific transcript 1 protein isoform 3: "Transcript Variant: This variant (3) includes an additional exon in the 5' UTR, lacks an alternate in-frame exon in the 5' coding region, and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1."<ref name=RefSeq7940/>
# NP_995311.2 leukocyte-specific transcript 1 protein isoform 4: "Transcript Variant: This variant (4) includes an additional exon in the 5' UTR and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (4) is shorter than isoform 1."<ref name=RefSeq7940/>
# NP_995312.2 leukocyte-specific transcript 1 protein isoform 5: "Transcript Variant: This variant (5) lacks an alternate exon in the central coding region and uses an alternate splice site that causes a frameshift in the 3' coding region, compared to variant 1. The encoded isoform (5) has a distinct C-terminus and is shorter than isoform 1. The 5' UTR of this variant is incomplete because the transcripts supporting this CDS exon combination lack a complete 5' UTR, and alternative splicing choices exist further upstream."<ref name=RefSeq7940/>
Gene ID: 8449 is DHX16 DEAH-box helicase 16 on 6p21.33: "DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is a functional homolog of fission yeast Prp8 protein involved in cell cycle progression. This gene is mapped to the MHC region on chromosome 6p21.3, a region where many malignant, genetic and autoimmune disease genes are linked. Three transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq8449>{{ cite web
|author=RefSeq
|title=DHX16 DEAH-box helicase 16 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=May 2018
|url=https://www.ncbi.nlm.nih.gov/gene/8449
|accessdate=11 April 2020 }}</ref>
# NP_001157711.1 pre-mRNA-splicing factor ATP-dependent RNA helicase DHX16 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1."<ref name=RefSeq8449/>
# NP_001350444.1 pre-mRNA-splicing factor ATP-dependent RNA helicase DHX16 isoform 3: "Transcript Variant: This variant (3) contains an alternate exon compared to variant 1. The resulting isoform (3) has a shorter and distinct N-terminus compared to isoform 1."<ref name=RefSeq8449/>
Gene ID: 8859 is [[STK19]] serine/threonine kinase 19 aka MHC class III HLA-RP1 on 6p21.33: "This gene encodes a serine/threonine kinase which localizes predominantly to the nucleus. Its specific function is unknown; it is possible that phosphorylation of this protein is involved in transcriptional regulation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6 and expresses two transcript variants."<ref name=RefSeq8859>{{ cite web
|author=RefSeq
|title=STK19 serine/threonine kinase 19 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/8859
|accessdate=6 April 2020 }}</ref>
# NP_004188.1 serine/threonine-protein kinase 19 isoform 1: "Transcript Variant: This variant (1) uses an alternate splice site in the coding region, compared to variant 2. It encodes isoform 1 which is shorter compared to isoform 2. Although isoforms 1 and 2 differ in the kinase domain, it appears that there is no difference in kinase activity between isoforms 1 and 2."<ref name=RefSeq8859/>
# NP_115830.1 serine/threonine-protein kinase 19 isoform 2: "Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (2). Although isoforms 1 and 2 differ in the kinase domain, it appears that there is no difference in kinase activity between isoforms 1 and 2."<ref name=RefSeq8859/>
Gene ID: 8870 is IER3 immediate early response 3 on 6p21.33: "This gene functions in the protection of cells from Fas- or tumor necrosis factor type alpha-induced apoptosis. Partially degraded and unspliced transcripts are found after virus infection in vitro, but these transcripts are not found in vivo and do not generate a valid protein."<ref name=RefSeq8870>{{ cite web
|author=RefSeq
|title=IER3 immediate early response 3 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/8870
|accessdate=11 April 2020 }}</ref>
Gene ID: 259197 is [[NCR3]] natural cytotoxicity triggering receptor 3 on 6p21.33: "The protein encoded by this gene is a natural cytotoxicity receptor (NCR) that may aid NK cells in the lysis of tumor cells. The encoded protein interacts with CD3-zeta (CD247), a T-cell receptor. A single nucleotide polymorphism in the 5' untranslated region of this gene has been associated with mild malaria suceptibility. Three transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq259197>{{ cite web
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=May 2010
|url=https://www.ncbi.nlm.nih.gov/gene/259197
|accessdate=6 April 2020 }}</ref>
# NP_001138938.1 natural cytotoxicity triggering receptor 3 isoform b: "Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region compared to variant 1, that results in a frameshift. It encodes isoform b, which has a shorter and distinct C-terminus compared to isoform a."<ref name=RefSeq259197/>
# NP_001138939.1 natural cytotoxicity triggering receptor 3 isoform c: "Transcript Variant: This variant (3) uses an alternate splice site in the 3' coding region compared to variant 1, that results in a frameshift. It encodes isoform c, which has a shorter and distinct C-terminus compared to isoform a."<ref name=RefSeq259197/>
# NP_667341.1 natural cytotoxicity triggering receptor 3 isoform a precursor: "Transcript Variant: This variant (1) encodes the longest isoform (a). [...] Ig; Immunoglobulin domain".<ref name=RefSeq259197/>
===Class IV===
===Class IV===
Several "genes have been described that are encoded in the telomeric end of the Class III region and that appear to be involved in both global and specific inflammatory responses. Due to this commonality of function this gene-rich region was dubbed Class IV, and includes the TNF family, AIF1, and HSP70."<ref name="gruen01"/>
Several "genes have been described that are encoded in the telomeric end of the Class III region and that appear to be involved in both global and specific inflammatory responses. Due to this commonality of function this gene-rich region was dubbed Class IV, and includes the TNF family, AIF1, and HSP70."<ref name="gruen01">{{cite journal |last1=Gruen |first1=JR |last2=Weissman |first2=SM |title=Human MHC class III and IV genes and disease associations |journal=Frontiers in Bioscience |date=2001 |volume=6 |issue=3 |pages=D960-172 |pmid=11487469 |url=https://www.bioscience.org/2001/v6/d/gruen/fulltext.htm|doi=10.2741/A658 }}</ref>
The B144/LST1 protein [...] is expressed in T cell, monocytic, and macrophage cell lines, and is also substantially expressed in both murine and human dendritic cells in culture."<ref name="gruen01"/>
The B144/LST1 protein [...] is expressed in T cell, monocytic, and macrophage cell lines, and is also substantially expressed in both murine and human dendritic cells in culture."<ref name="gruen01"/>
Line 961:
Line 148:
"The existence of the G1 gene was initially noted as a part of a screen of MHC cosmids for embedded genes. The G1 and AIF1 transcripts appear to be derived by alternative splicing from partially overlapping genomic templates. A third human interferon gamma-responsive transcript, IRT-1, has been noted that shares some internal sequences with both G1 and AIF1, but on the basis of the predicted open reading frame it shares only limited amino acid sequences with G1."<ref name="gruen01"/>
"The existence of the G1 gene was initially noted as a part of a screen of MHC cosmids for embedded genes. The G1 and AIF1 transcripts appear to be derived by alternative splicing from partially overlapping genomic templates. A third human interferon gamma-responsive transcript, IRT-1, has been noted that shares some internal sequences with both G1 and AIF1, but on the basis of the predicted open reading frame it shares only limited amino acid sequences with G1."<ref name="gruen01"/>
Gene ID: 199 is AIF1 allograft inflammatory factor 1 on 6p21.33: "This gene encodes a protein that binds actin and calcium. This gene is induced by cytokines and interferon and may promote macrophage activation and growth of vascular smooth muscle cells and T-lymphocytes. Polymorphisms in this gene may be associated with systemic sclerosis. Alternative splicing results in multiple transcript variants, but the full-length and coding nature of some of these variants is not certain."<ref name=RefSeq199>{{ cite web
Gene ID: 199 is AIF1 [[allograft inflammatory factor 1]] on 6p21.33: "This gene encodes a protein that binds actin and calcium. This gene is induced by cytokines and interferon and may promote macrophage activation and growth of vascular smooth muscle cells and T-lymphocytes. Polymorphisms in this gene may be associated with systemic sclerosis. Alternative splicing results in multiple transcript variants, but the full-length and coding nature of some of these variants is not certain."<ref name=RefSeq199>{{ cite web
|author=RefSeq
|author=RefSeq
|title=AIF1 allograft inflammatory factor 1 [ Homo sapiens (human) ]
|title=AIF1 allograft inflammatory factor 1 [ Homo sapiens (human) ]
Line 1,001:
Line 188:
|url=https://www.ncbi.nlm.nih.gov/gene/3305
|url=https://www.ncbi.nlm.nih.gov/gene/3305
|accessdate=6 April 2020 }}</ref>
|accessdate=6 April 2020 }}</ref>
Gene ID: 3309 is [[Binding immunoglobulin protein|HSPA5]] heat shock protein family A (Hsp70) member 5 on 9q33.3: "The protein encoded by this gene is a member of the heat shock protein 70 (HSP70) family. It is localized in the lumen of the endoplasmic reticulum (ER), and is involved in the folding and assembly of proteins in the ER. As this protein interacts with many ER proteins, it may play a key role in monitoring protein transport through the cell."<ref name=RefSeq3309>{{ cite web
|author=RefSeq
|title=HSPA5 heat shock protein family A (Hsp70) member 5 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
Gene ID: 6892 is [[Tapasin|TAPBP]] TAP binding protein on 6p21.32: "This gene encodes a transmembrane glycoprotein which mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction is essential for optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and this protein may be bound to a single TAP molecule. This protein contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. This gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms."<ref name=RefSeq6892>{{ cite web
Gene ID: 6892 is [[Tapasin|TAPBP]] TAP binding protein on 6p21.32: "This gene encodes a transmembrane glycoprotein which mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction is essential for optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and this protein may be bound to a single TAP molecule. This protein contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. This gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms."<ref name=RefSeq6892>{{ cite web
Line 1,013:
Line 210:
# NP_757345.2 tapasin isoform 2 precursor: "Transcript Variant: This variant (2) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (2) has a distinct C-terminus and is longer than isoform 1."<ref name=RefSeq6892/>
# NP_757345.2 tapasin isoform 2 precursor: "Transcript Variant: This variant (2) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (2) has a distinct C-terminus and is longer than isoform 1."<ref name=RefSeq6892/>
# NP_757346.2 tapasin isoform 3 precursor: "Transcript Variant: This variant (3) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (3) that is shorter than isoform 1."<ref name=RefSeq6892/>
# NP_757346.2 tapasin isoform 3 precursor: "Transcript Variant: This variant (3) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (3) that is shorter than isoform 1."<ref name=RefSeq6892/>
Gene ID: 23640 is HSPBP1 HSPA (Hsp70) binding protein 1 on 19q13.42.<ref name=HGNC23640>{{ cite web
|author=HGNC
|title=HSPBP1 HSPA (Hsp70) binding protein 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=3 May 2020
|url=https://www.ncbi.nlm.nih.gov/gene/23640
|accessdate=8 May 2020 }}</ref>
# NP_001123578.1 hsp70-binding protein 1 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon, compared to variant 3. Variants 1 and 2 encode the same isoform (2), which has a shorter N-terminus, compared to isoform 1."<ref name=HGNC23640/>
# NP_001284529.1 hsp70-binding protein 1 isoform 1: "Transcript Variant: This variant (3) encodes the longer isoform (1)."<ref name=HGNC23640/>
# NP_036399.3 hsp70-binding protein 1 isoform 2: "Transcript Variant: This variant (1) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon, compared to variant 3. Variants 1 and 2 encode the same isoform (2), which has a shorter N-terminus, compared to isoform 1."<ref name=HGNC23640/>
===Class V===
===Class V===
Line 1,018:
Line 227:
"Vacuolar ATPase is a multi-subunit protein complex that transports H<sup>+</sup> ions. It functions in general to mediate acidification of cellular vacuoles, and consequently in receptor recycling, lysosome formation, and cellular pH control. [Sequences] centromeric to the BAT1 gene [...] encode exons of a gene, ATP6G, homologous to the G subunit of the vacuolar H<sup>+</sup> ATPase of a number of species.(26) The mRNA for this gene had two alternative splice forms, with the shorter form removing the presumptive translation initiation codon of the longer form and therefore removing an amino terminal region of high homology to other G subunits. The longer splice form was selectively expressed in some B and T cell lines as compared with myelomonocytic lines. Vacuolar ATPase subunit G is up-regulated in neutrophils exposed to non-pathogenic bacteria (Yeramilli and Weissman, unpublished). The ATPase is also up-regulated in neutrophils by GM-CSF or phorbol myristic acid. Up-regulation of the ATPase is one of the mechanisms that may delay apoptosis in activated neutrophils. However a specific role for the ATP6G in inflammation remains to be established by more specific means."<ref name="gruen01"/>
"Vacuolar ATPase is a multi-subunit protein complex that transports H<sup>+</sup> ions. It functions in general to mediate acidification of cellular vacuoles, and consequently in receptor recycling, lysosome formation, and cellular pH control. [Sequences] centromeric to the BAT1 gene [...] encode exons of a gene, ATP6G, homologous to the G subunit of the vacuolar H<sup>+</sup> ATPase of a number of species.(26) The mRNA for this gene had two alternative splice forms, with the shorter form removing the presumptive translation initiation codon of the longer form and therefore removing an amino terminal region of high homology to other G subunits. The longer splice form was selectively expressed in some B and T cell lines as compared with myelomonocytic lines. Vacuolar ATPase subunit G is up-regulated in neutrophils exposed to non-pathogenic bacteria (Yeramilli and Weissman, unpublished). The ATPase is also up-regulated in neutrophils by GM-CSF or phorbol myristic acid. Up-regulation of the ATPase is one of the mechanisms that may delay apoptosis in activated neutrophils. However a specific role for the ATP6G in inflammation remains to be established by more specific means."<ref name="gruen01"/>
Gene ID: 534 is ATP6V1G2 ATPase H+ transporting V1 subunit G2 on 6p21.33: "This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of three V1 domain G subunit proteins. This gene had previous gene symbols of ATP6G and ATP6G2. Alternatively spliced transcript variants encoding different isoforms have been described. Read-through transcription also exists between this gene and the downstream DEAD (Asp-Glu-Ala-Asp) box polypeptide 39B (DDX39B) gene."<ref name=RefSeq534>{{ cite web
Gene ID: 534 is [[ATP6V1G2]] ATPase H+ transporting V1 subunit G2 on 6p21.33: "This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of three V1 domain G subunit proteins. This gene had previous gene symbols of ATP6G and ATP6G2. Alternatively spliced transcript variants encoding different isoforms have been described. Read-through transcription also exists between this gene and the downstream DEAD (Asp-Glu-Ala-Asp) box polypeptide 39B (DDX39B) gene."<ref name=RefSeq534>{{ cite web
Gene ID: 7916 is PRRC2A proline rich coiled-coil 2A aka G2; BAT2; D6S51; D6S51E on 6p21.33: "A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. These genes are all within the human major histocompatibility complex class III region. This gene has microsatellite repeats which are associated with the age-at-onset of insulin-dependent diabetes mellitus (IDDM) and possibly thought to be involved with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. This gene is also a candidate gene for the development of rheumatoid arthritis. Two transcript variants encoding the same protein have been found for this gene."<ref name=RefSeq7916>{{ cite web
Gene ID: 7916 is PRRC2A proline rich coiled-coil 2A aka G2; [[BAT2]]; D6S51; D6S51E on 6p21.33: "A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. These genes are all within the human major histocompatibility complex class III region. This gene has microsatellite repeats which are associated with the age-at-onset of insulin-dependent diabetes mellitus (IDDM) and possibly thought to be involved with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. This gene is also a candidate gene for the development of rheumatoid arthritis. Two transcript variants encoding the same protein have been found for this gene."<ref name=RefSeq7916>{{ cite web
# NP_542417.2 protein PRRC2A: "Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 2. Variants 1 and 2 both encode the same protein."<ref name=RefSeq7916/>
# NP_542417.2 protein PRRC2A: "Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 2. Variants 1 and 2 both encode the same protein."<ref name=RefSeq7916/>
Gene ID: 7917 is BAG6 BAG cochaperone 6 aka G3; BAT3 on 6p21.33: "This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq7917>{{ cite web
Gene ID: 7917 is [[HLA-B associated transcript 3|BAG6]] BAG cochaperone 6 aka G3; BAT3 on 6p21.33: "This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq7917>{{ cite web
|author=RefSeq
|author=RefSeq
|title=BAG6 BAG cochaperone 6 [ Homo sapiens (human) ]
|title=BAG6 BAG cochaperone 6 [ Homo sapiens (human) ]
Line 1,055:
Line 264:
# NP_542434.1 large proline-rich protein BAG6 isoform b: "Transcript Variant: This variant (3) utilizes an alternative in-frame splice site in the 5' coding region, compared to variant 1. Variants 2, 3, and 4 encode the same isoform (b), which is 6 aa shorter than isoform a."<ref name=RefSeq7917/>
# NP_542434.1 large proline-rich protein BAG6 isoform b: "Transcript Variant: This variant (3) utilizes an alternative in-frame splice site in the 5' coding region, compared to variant 1. Variants 2, 3, and 4 encode the same isoform (b), which is 6 aa shorter than isoform a."<ref name=RefSeq7917/>
Gene ID: 7918 is GPANK1 G-patch domain and ankyrin repeats 1 aka G5; BAT4, on 6p21.33: "This gene is located in a cluster of HLA-B-associated transcripts, which is included in the human major histocompatability complex III region. This gene encodes a protein which is thought to play a role in immunity. Multiple alternatively spliced variants, encoding the same protein, have been identified."<ref name=RefSeq7918>{{ cite web
Gene ID: 7918 is GPANK1 G-patch domain and ankyrin repeats 1 aka G5; [[BAT4]], on 6p21.33: "This gene is located in a cluster of HLA-B-associated transcripts, which is included in the human major histocompatability complex III region. This gene encodes a protein which is thought to play a role in immunity. Multiple alternatively spliced variants, encoding the same protein, have been identified."<ref name=RefSeq7918>{{ cite web
|author=RefSeq
|author=RefSeq
|title=GPANK1 G-patch domain and ankyrin repeats 1 [ Homo sapiens (human) ]
|title=GPANK1 G-patch domain and ankyrin repeats 1 [ Homo sapiens (human) ]
Line 1,069:
Line 278:
# NP_149417.1 G patch domain and ankyrin repeat-containing protein 1: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein."<ref name=RefSeq7918/>
# NP_149417.1 G patch domain and ankyrin repeat-containing protein 1: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein."<ref name=RefSeq7918/>
Gene ID: 7919 is DDX39B DExD-box helicase 39B aka BAT1 on 6p21.33: "This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and it also plays an important role in mRNA export from the nucleus to the cytoplasm. This gene belongs to a cluster of genes localized in the vicinity of the genes encoding tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on both chromosomes 6 and 11. Read-through transcription also occurs between this gene and the upstream ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) gene."<ref name=RefSeq7919>{{ cite web
Gene ID: 7919 is DDX39B DExD-box helicase 39B aka [[BAT1]] on 6p21.33: "This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and it also plays an important role in mRNA export from the nucleus to the cytoplasm. This gene belongs to a cluster of genes localized in the vicinity of the genes encoding tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on both chromosomes 6 and 11. Read-through transcription also occurs between this gene and the upstream ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) gene."<ref name=RefSeq7919>{{ cite web
|author=RefSeq
|author=RefSeq
|title=DDX39B DExD-box helicase 39B [ Homo sapiens (human) ]
|title=DDX39B DExD-box helicase 39B [ Homo sapiens (human) ]
Line 1,080:
Line 289:
# NP_542165.1 spliceosome RNA helicase DDX39B: "Transcript Variant: This variant (2) uses an alternative splice site in the 5' UTR, compared to variant 1. Both variants 1 and 2 encode the same protein."<ref name=RefSeq7919/>
# NP_542165.1 spliceosome RNA helicase DDX39B: "Transcript Variant: This variant (2) uses an alternative splice site in the 5' UTR, compared to variant 1. Both variants 1 and 2 encode the same protein."<ref name=RefSeq7919/>
Gene ID: 7920 is ABHD16A abhydrolase domain containing 16A, phospholipase, aka BAT5 on 6p21.33: "A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. The protein encoded by this gene is thought to be involved in some aspects of immunity. Alternatively spliced transcript variants have been described."<ref name=RefSeq7920>{{ cite web
Gene ID: 7920 is ABHD16A abhydrolase domain containing 16A, phospholipase, aka [[BAT5]] on 6p21.33: "A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. The protein encoded by this gene is thought to be involved in some aspects of immunity. Alternatively spliced transcript variants have been described."<ref name=RefSeq7920>{{ cite web
The region within the MHC class III gene cluster that contains genes for TNFs is also known as MHC class VI or the inflammatory region.<ref name="deakin">{{cite journal |last1=Deakin |first1=Janine E |last2=Papenfuss |first2=Anthony T |last3=Belov |first3=Katherine |last4=Cross |first4=Joseph GR |last5=Coggill |first5=Penny |last6=Palmer |first6=Sophie |last7=Sims |first7=Sarah |last8=Speed |first8=Terence P |last9=Beck |first9=Stephan |last10=Graves |first10=Jennifer |title=Evolution and comparative analysis of the MHC Class III inflammatory region |journal=BMC Genomics |date=2006 |volume=7 |issue=1 |pages=281 |doi=10.1186/1471-2164-7-281 |pmid=17081307 |pmc=1654159}}</ref>
The region within the MHC class III gene cluster that contains genes for TNFs is also known as MHC class VI or the inflammatory region.<ref name="deakin">{{cite journal |last1=Deakin |first1=Janine E |last2=Papenfuss |first2=Anthony T |last3=Belov |first3=Katherine |last4=Cross |first4=Joseph GR |last5=Coggill |first5=Penny |last6=Palmer |first6=Sophie |last7=Sims |first7=Sarah |last8=Speed |first8=Terence P |last9=Beck |first9=Stephan |last10=Graves |first10=Jennifer |title=Evolution and comparative analysis of the MHC Class III inflammatory region |journal=BMC Genomics |date=2006 |volume=7 |issue=1 |pages=281 |doi=10.1186/1471-2164-7-281 |pmid=17081307 |pmc=1654159}}</ref>
Gene ID: 4049 is LTA lymphotoxin alpha on 6p21.33: "The encoded protein, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The protein is highly inducible, secreted, and forms heterotrimers with lymphotoxin-beta which anchor lymphotoxin-alpha to the cell surface. This protein also mediates a large variety of inflammatory, immunostimulatory, and antiviral responses, is involved in the formation of secondary lymphoid organs during development and plays a role in apoptosis. Genetic variations in this gene are associated with susceptibility to leprosy type 4, myocardial infarction, non-Hodgkin's lymphoma, and psoriatic arthritis. Alternatively spliced transcript variants have been observed for this gene."<ref name=RefSeq4049>{{ cite web
Gene ID: 4049 is LTA [[lymphotoxin alpha]] on 6p21.33: "The encoded protein, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The protein is highly inducible, secreted, and forms heterotrimers with lymphotoxin-beta which anchor lymphotoxin-alpha to the cell surface. This protein also mediates a large variety of inflammatory, immunostimulatory, and antiviral responses, is involved in the formation of secondary lymphoid organs during development and plays a role in apoptosis. Genetic variations in this gene are associated with susceptibility to leprosy type 4, myocardial infarction, non-Hodgkin's lymphoma, and psoriatic arthritis. Alternatively spliced transcript variants have been observed for this gene."<ref name=RefSeq4049>{{ cite web
|author=RefSeq
|author=RefSeq
|title=LTA lymphotoxin alpha [ Homo sapiens (human) ]
|title=LTA lymphotoxin alpha [ Homo sapiens (human) ]
Line 1,110:
Line 319:
# NP_001153212.1 lymphotoxin-alpha precursor: "Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein."<ref name=RefSeq4049/>
# NP_001153212.1 lymphotoxin-alpha precursor: "Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein."<ref name=RefSeq4049/>
Gene ID: 4050 is LTB lymphotoxin beta on 6p21.33: "Lymphotoxin beta is a type II membrane protein of the TNF family. It anchors lymphotoxin-alpha to the cell surface through heterotrimer formation. The predominant form on the lymphocyte surface is the lymphotoxin-alpha 1/beta 2 complex (e.g. 1 molecule alpha/2 molecules beta) and this complex is the primary ligand for the lymphotoxin-beta receptor. The minor complex is lymphotoxin-alpha 2/beta 1. LTB is an inducer of the inflammatory response system and involved in normal development of lymphoid tissue. Lymphotoxin-beta isoform b is unable to complex with lymphotoxin-alpha suggesting a function for lymphotoxin-beta which is independent of lympyhotoxin-alpha. Alternative splicing results in multiple transcript variants encoding different isoforms."<ref name=RefSeq4050>{{ cite web
Gene ID: 4050 is LTB [[lymphotoxin beta]] on 6p21.33: "Lymphotoxin beta is a type II membrane protein of the TNF family. It anchors lymphotoxin-alpha to the cell surface through heterotrimer formation. The predominant form on the lymphocyte surface is the lymphotoxin-alpha 1/beta 2 complex (e.g. 1 molecule alpha/2 molecules beta) and this complex is the primary ligand for the lymphotoxin-beta receptor. The minor complex is lymphotoxin-alpha 2/beta 1. LTB is an inducer of the inflammatory response system and involved in normal development of lymphoid tissue. Lymphotoxin-beta isoform b is unable to complex with lymphotoxin-alpha suggesting a function for lymphotoxin-beta which is independent of lympyhotoxin-alpha. Alternative splicing results in multiple transcript variants encoding different isoforms."<ref name=RefSeq4050>{{ cite web
|author=RefSeq
|author=RefSeq
|title=LTB lymphotoxin beta [ Homo sapiens (human) ]
|title=LTB lymphotoxin beta [ Homo sapiens (human) ]
Line 1,132:
Line 341:
===ATP-binding cassette (ABC) transporters===
===ATP-binding cassette (ABC) transporters===
Gene ID: 23 is ABCF1 ATP binding cassette subfamily F member 1, on 6p21.33: "The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the GCN20 subfamily. Unlike other members of the superfamily, this protein lacks the transmembrane domains which are characteristic of most ABC transporters. This protein may be regulated by tumor necrosis factor-alpha and play a role in enhancement of protein synthesis and the inflammation process."<ref name=RefSeq23>{{ cite web
Gene ID: 23 is [[ABCF1]] ATP binding cassette subfamily F member 1, on 6p21.33: "The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the GCN20 subfamily. Unlike other members of the superfamily, this protein lacks the transmembrane domains which are characteristic of most ABC transporters. This protein may be regulated by tumor necrosis factor-alpha and play a role in enhancement of protein synthesis and the inflammation process."<ref name=RefSeq23>{{ cite web
|author=RefSeq
|author=RefSeq
|title=ABCF1 ATP binding cassette subfamily F member 1 [ Homo sapiens (human) ]
|title=ABCF1 ATP binding cassette subfamily F member 1 [ Homo sapiens (human) ]
Line 1,139:
Line 348:
|date=July 2008
|date=July 2008
|url=https://www.ncbi.nlm.nih.gov/gene/23
|url=https://www.ncbi.nlm.nih.gov/gene/23
|accessdate=7 April 2020 }}</ref>
|accessdate=7 April 2020 }}</ref> No immunoglobulins.<ref name=RefSeq23/>
# NP_001020262.1 ATP-binding cassette sub-family F member 1 isoform a: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a)."<ref name=RefSeq23/>
# NP_001020262.1 ATP-binding cassette sub-family F member 1 isoform a: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a)."<ref name=RefSeq23/>
# NP_001081.1 ATP-binding cassette sub-family F member 1 isoform b: "Transcript Variant: This variant (2) lacks an alternate in-frame exon, compared to variant 1. The resulting protein (isoform b) is shorter than isoform a."<ref name=RefSeq23/>
# NP_001081.1 ATP-binding cassette sub-family F member 1 isoform b: "Transcript Variant: This variant (2) lacks an alternate in-frame exon, compared to variant 1. The resulting protein (isoform b) is shorter than isoform a."<ref name=RefSeq23/>
Gene ID: 6890 is [[TAP1|TAP1]] transporter 1, ATP binding cassette subfamily B member aka transporter, ATP-binding cassette, major histocompatibility complex, 1 on 6p21.32: "The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Two transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq2014M>{{ cite web
Gene ID: 6890 is [[TAP1|TAP1]] transporter 1, ATP binding cassette subfamily B member aka transporter, ATP-binding cassette, major histocompatibility complex, 1 on 6p21.32: "The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Two transcript variants encoding different isoforms have been found for this gene."<ref name=RefSeq6890>{{ cite web
|author=RefSeq
|author=RefSeq
|title=TAP1 transporter 1, ATP binding cassette subfamily B member [ Homo sapiens (human) ]
|title=TAP1 transporter 1, ATP binding cassette subfamily B member [ Homo sapiens (human) ]
Line 1,150:
Line 359:
|date=May 2014
|date=May 2014
|url=https://www.ncbi.nlm.nih.gov/gene/6890
|url=https://www.ncbi.nlm.nih.gov/gene/6890
|accessdate=1 April 2020 }}</ref>
|accessdate=1 April 2020 }}</ref> No immunoglobulins.<ref name=RefSeq6890/>
# NP_000584.3 antigen peptide transporter 1 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."<ref name=RefSeq2014M/>
# NP_000584.3 antigen peptide transporter 1 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."<ref name=RefSeq6890/>
# NP_001278951.1 antigen peptide transporter 1 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1."<ref name=RefSeq2014M/>
# NP_001278951.1 antigen peptide transporter 1 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1."<ref name=RefSeq6890/>
Gene ID: 6891 is [[TAP2]] transporter 2, ATP binding cassette subfamily B member on 6p21.32: "The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. This gene is located 7 kb telomeric to gene family member ABCB2. The protein encoded by this gene is involved in antigen presentation. This protein forms a heterodimer with ABCB2 in order to transport peptides from the cytoplasm to the endoplasmic reticulum. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Alternative splicing of this gene produces products which differ in peptide selectivity and level of restoration of surface expression of MHC class I molecules."<ref name=RefSeq6891>{{ cite web
Gene ID: 6891 is [[TAP2]] transporter 2, ATP binding cassette subfamily B member on 6p21.32: "The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. This gene is located 7 kb telomeric to gene family member ABCB2. The protein encoded by this gene is involved in antigen presentation. This protein forms a heterodimer with ABCB2 in order to transport peptides from the cytoplasm to the endoplasmic reticulum. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Alternative splicing of this gene produces products which differ in peptide selectivity and level of restoration of surface expression of MHC class I molecules."<ref name=RefSeq6891>{{ cite web
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|date=February 2014
|date=February 2014
|url=https://www.ncbi.nlm.nih.gov/gene/6891
|url=https://www.ncbi.nlm.nih.gov/gene/6891
|accessdate=6 April 2020 }}</ref>
|accessdate=6 April 2020 }}</ref> No immunoglobulins.<ref name=RefSeq6891/>
# NP_000535.3 antigen peptide transporter 2 isoform 1: "Transcript Variant: This variant (1, B allele) represents the longer transcript and encodes the longest isoform (1). An allele (variant 1, A allele) exists in which a single nt change creates an internal stop codon, leading to a protein that is 17 aa shorter at the C-terminus."<ref name=RefSeq6891/>
# NP_000535.3 antigen peptide transporter 2 isoform 1: "Transcript Variant: This variant (1, B allele) represents the longer transcript and encodes the longest isoform (1). An allele (variant 1, A allele) exists in which a single nt change creates an internal stop codon, leading to a protein that is 17 aa shorter at the C-terminus."<ref name=RefSeq6891/>
# NP_001276972.1 antigen peptide transporter 2 isoform 3: "Transcript Variant: This variant (1, A allele) differs at 3 nt positions compared to variant 1, B allele. The resulting isoform (3) is shorter at the C-terminus compared to isoform 1."<ref name=RefSeq6891/>
# NP_001276972.1 antigen peptide transporter 2 isoform 3: "Transcript Variant: This variant (1, A allele) differs at 3 nt positions compared to variant 1, B allele. The resulting isoform (3) is shorter at the C-terminus compared to isoform 1."<ref name=RefSeq6891/>
# NP_061313.2 antigen peptide transporter 2 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding region compared to variant 1. The resulting isoform (2) is shorter and has a distinct C-terminus compared to isoform 1."<ref name=RefSeq6891/>
# NP_061313.2 antigen peptide transporter 2 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding region compared to variant 1. The resulting isoform (2) is shorter and has a distinct C-terminus compared to isoform 1."<ref name=RefSeq6891/>
===NF-kappa-B inhibitor family===
===Immunoglobulin domain genes===
{{main|Immunoglobulin domain genes}}
Gene ID: 4792 is [[IκBα|NFKBIA]] NFKB inhibitor alpha aka major histocompatibility complex enhancer-binding protein [mitotic arrest deficient 3] MAD3 on 14q13.2: "This gene encodes a member of the NF-kappa-B inhibitor family, which contain multiple ankrin repeat domains. The encoded protein interacts with REL dimers to inhibit NF-kappa-B/REL complexes which are involved in inflammatory responses. The encoded protein moves between the cytoplasm and the nucleus via a nuclear localization signal and CRM1-mediated nuclear export. Mutations in this gene have been found in ectodermal dysplasia anhidrotic with T-cell immunodeficiency autosomal dominant disease."<ref name=RefSeq2011Au>{{ cite web
|title=NFKBIA NFKB inhibitor alpha [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=August 2011
|url=https://www.ncbi.nlm.nih.gov/gene/4792
|accessdate=28 March 2020 }}</ref>
===ZAS family===
===ZAS family===
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{{div col|colwidth=20em}}
{{div col|colwidth=20em}}
* [[Alpha-1-B glycoprotein]]
* [[Alpha-1-B glycoprotein]]
* [[Nuclear factor gene transcriptions]]
* [[SCAN domain]]
* [[SCAN domain]]
{{Div col end}}
{{Div col end}}
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<!-- footer categories -->
<!-- footer categories -->
[[Category:Resources last modified in April 2020]]
[[Category:Resources last modified in July 2020]]
Latest revision as of 00:14, 3 July 2020
Associate Editor(s)-in-Chief: Henry A. Hoff
The immunoglobulin supergene family is "the group of proteins that have immunoglobulin-like domains, including histocompatibility antigens, the T-cell antigen receptor, poly-IgR, and other proteins involved in the vertebrate immune response (17)."[1]
Gene ID: 1 A1BG alpha-1-B glycoprotein on 19q13.43: "The protein encoded by this gene is a plasma glycoprotein of unknown function. The protein shows sequence similarity to the variable regions of some immunoglobulin supergene family member proteins."[2]
NP_570602.2 alpha-1B-glycoprotein precursor, Conserved Domains (4) summary: cd05751 Location: 401 → 493 Ig1_LILRB1_like; First immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors (LILR)B1 (also known as LIR-1) and similar proteins, smart00410 Location: 218 → 280 IG_like; Immunoglobulin like, pfam13895 Location: 210 → 301 Ig_2; Immunoglobulin domain and cl11960 Location: 28 → 110 Ig; Immunoglobulin domain.[2]
A1BG contains the immunoglobulin domain: cl11960 and three immunoglobulin-like domains: pfam13895, cd05751 and smart00410.
"Immunoglobulin (Ig) domain [cl11960] found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond."[3]
"Ig1_LILR_KIR_like: [cd05751] domain similar to the first immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors (LILRs) and Natural killer inhibitory receptors (KIRs). This group includes LILRB1 (or LIR-1), LILRA5 (or LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (or CD89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3,and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1 (LIR-1), LILRB2 (LIR-2), and LILRB3 (LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LIR-1 (LILRB1), and LIR-2 (LILRB2), show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1 (LIR-1), and LILRB2 (LIR-2), and two in the case of LILRB4 (LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst."[5]
"IG domains [smart00410] that cannot be classified into one of IGv1, IGc1, IGc2, IG."[6]
"𝛂1B-glycoprotein(𝛂1B) [...] consists of a single polypeptide chain N-linked to four
glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues. [...] 𝛂1B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond. [...] several domains of 𝛂1B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. 𝛂1B [...] exhibits sequence similarity to other members of the immunoglobulin supergene family such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA."[1]
"Some of the domains of 𝛂1B show significant homology to variable (V) and constant (C) regions of certain immunoglobulins. Likewise, there is statistically significant homology between 𝛂1B and the secretory component (SC) of human IgA (15) and also with the extracellular portion of the rabbit receptor for transepithelial transport of polymeric immunoglobulins (IgA and IgM). Mostov et al. (16) have called the later protein the poly-Ig receptor or poly-IgR and have shown that it is the precursor of SC."[1]
Gene ID: 7441 is VPREB1 V-set pre-B cell surrogate light chain 1 on 22q11.22: "The protein encoded by this gene belongs to the immunoglobulin superfamily and is expressed selectively at the early stages of B cell development, namely, in proB and early preB cells. This gene encodes the iota polypeptide chain that is associated with the Ig-mu chain to form a molecular complex which is expressed on the surface of pre-B cells. The complex is thought to regulate Ig gene rearrangements in the early steps of B-cell differentiation. Alternative splicing results in multiple transcript variants."[7]
NP_001290438.1 immunoglobulin iota chain isoform 2: "Transcript Variant: This variant (2) uses an alternate splice site in the coding region and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1."[7] Conserved Domains summary: smart00410 Location: 25 → 115 IG_like; Immunoglobulin like and cl11960 Location: 29 → 117 Ig; Immunoglobulin domain.[7]
NP_009059.1 immunoglobulin iota chain isoform 1 precursor: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."[7] Conserved Domains summary: smart00410 Location: 26 → 116 IG_like; Immunoglobulin like and cl11960 Location: 30 → 118 Ig; Immunoglobulin domain.[7]
Gene ID: 29802 is VPREB3 V-set pre-B cell surrogate light chain 3 on 22q11.23; 22q11: "The protein encoded by this gene is the human ortholog of the mouse VpreB3 (8HS20) protein, is thought to be involved in B-cell maturation, and may play a role in assembly of the pre-B cell receptor (pre-BCR). While the role of this protein in B-cell development has not yet been elucidated, studies with the chicken ortholog of this protein have found that when overexpressed, this protein localizes to the endoplasmic reticulum. The mouse ortholog of this protein has been shown to associate with membrane mu heavy chains early in the course of pre-B cell receptor biosynthesis. Expression of this gene has been observed in some lymphomas."[8]
Several "genes have been described that are encoded in the telomeric end of the Class III region and that appear to be involved in both global and specific inflammatory responses. Due to this commonality of function this gene-rich region was dubbed Class IV, and includes the TNF family, AIF1, and HSP70."[9]
The B144/LST1 protein [...] is expressed in T cell, monocytic, and macrophage cell lines, and is also substantially expressed in both murine and human dendritic cells in culture."[9]
"The 1C7 gene [...] is located immediately adjacent to the B144 gene. RNA for B144 and 1C7 are transcribed in convergent directions such that there is a slight overlap between the 3' ends of the two mRNAs. [Human] 1C7 also shows multiple splice forms with 9 forms of the human mRNA reported so far.(21) The major forms encode proteins containing a leader sequence, a probable trans-membrane segment, an external sequence including an immunoglobulin-like domain, and at least three alternative forms of the putative intracellular segment of the protein. One alternative splice modifies the structure of the immunoglobulin-like domain, changing it from a sequence more closely resembling those of the V regions of Ig molecules to one that is more similar to IgC2 regions. Of the three alternative putative intracellular domains, one encodes multiple proline repeats suggestive of SH3 binding domains."[9]
"The existence of the G1 gene was initially noted as a part of a screen of MHC cosmids for embedded genes. The G1 and AIF1 transcripts appear to be derived by alternative splicing from partially overlapping genomic templates. A third human interferon gamma-responsive transcript, IRT-1, has been noted that shares some internal sequences with both G1 and AIF1, but on the basis of the predicted open reading frame it shares only limited amino acid sequences with G1."[9]
Gene ID: 199 is AIF1 allograft inflammatory factor 1 on 6p21.33: "This gene encodes a protein that binds actin and calcium. This gene is induced by cytokines and interferon and may promote macrophage activation and growth of vascular smooth muscle cells and T-lymphocytes. Polymorphisms in this gene may be associated with systemic sclerosis. Alternative splicing results in multiple transcript variants, but the full-length and coding nature of some of these variants is not certain."[10]
NP_001305899.1 allograft inflammatory factor 1 isoform 1: "Transcript Variant: This variant (4) uses an alternate splice site in the 5' region and initiates translation at a downstream start codon compared to variant 3. The encoded isoform (1) has a shorter N-terminus than isoform 3. Variants 1 and 4 encode the same isoform (1)."[10]
NP_001614.3 allograft inflammatory factor 1 isoform 3: "Transcript Variant: This variant (3) encodes the longest isoform (3)."[10]
NP_116573.1 allograft inflammatory factor 1 isoform 1: "Transcript Variant: This variant (1, also known as G1) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon compared to variant 3. The encoded isoform (1) has a shorter N-terminus than isoform 3. Variants 1 and 4 encode the same isoform (1)."[10]
"AIF-1 (allograft inflammatory factor-1) is a Ca2+ binding protein predominantly expressed by activated monocytes, originally identified in rat cardiac allografts with chronic rejection.(22) The human cDNA homologue is 86% identical to the rat (90% identical to the amino acid sequence) and was identified by reverse transcriptase-PCR of endomyocardial biopsy specimens from human heart transplants and in macrophage cell lines.(23)"[9]
Gene ID: 3303 is HSPA1A heat shock protein family A (Hsp70) member 1A on 6p21.33: "This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins."[11]
Gene ID: 3304 is HSPA1B heat shock protein family A (Hsp70) member 1B on 6p21.33: "This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins."[12]
Gene ID: 3305 is HSPA1L heat shock protein family A (Hsp70) member 1 like on 6p21.33: "This gene encodes a 70kDa heat shock protein. In conjunction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which also encode isoforms of the 70kDa heat shock protein."[13]
Gene ID: 3309 is HSPA5 heat shock protein family A (Hsp70) member 5 on 9q33.3: "The protein encoded by this gene is a member of the heat shock protein 70 (HSP70) family. It is localized in the lumen of the endoplasmic reticulum (ER), and is involved in the folding and assembly of proteins in the ER. As this protein interacts with many ER proteins, it may play a key role in monitoring protein transport through the cell."[14]
Gene ID: 6892 is TAPBP TAP binding protein on 6p21.32: "This gene encodes a transmembrane glycoprotein which mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction is essential for optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and this protein may be bound to a single TAP molecule. This protein contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. This gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms."[15]
NP_003181.3 tapasin isoform 1 precursor: "Transcript Variant: This variant (1) represents the longest transcript and encodes isoform 1. [...] Ig; Immunoglobulin domain"[15]
NP_757345.2 tapasin isoform 2 precursor: "Transcript Variant: This variant (2) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (2) has a distinct C-terminus and is longer than isoform 1."[15]
NP_757346.2 tapasin isoform 3 precursor: "Transcript Variant: This variant (3) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (3) that is shorter than isoform 1."[15]
Gene ID: 23640 is HSPBP1 HSPA (Hsp70) binding protein 1 on 19q13.42.[16]
NP_001123578.1 hsp70-binding protein 1 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon, compared to variant 3. Variants 1 and 2 encode the same isoform (2), which has a shorter N-terminus, compared to isoform 1."[16]
NP_001284529.1 hsp70-binding protein 1 isoform 1: "Transcript Variant: This variant (3) encodes the longer isoform (1)."[16]
NP_036399.3 hsp70-binding protein 1 isoform 2: "Transcript Variant: This variant (1) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon, compared to variant 3. Variants 1 and 2 encode the same isoform (2), which has a shorter N-terminus, compared to isoform 1."[16]
Class V
"Vacuolar ATPase is a multi-subunit protein complex that transports H+ ions. It functions in general to mediate acidification of cellular vacuoles, and consequently in receptor recycling, lysosome formation, and cellular pH control. [Sequences] centromeric to the BAT1 gene [...] encode exons of a gene, ATP6G, homologous to the G subunit of the vacuolar H+ ATPase of a number of species.(26) The mRNA for this gene had two alternative splice forms, with the shorter form removing the presumptive translation initiation codon of the longer form and therefore removing an amino terminal region of high homology to other G subunits. The longer splice form was selectively expressed in some B and T cell lines as compared with myelomonocytic lines. Vacuolar ATPase subunit G is up-regulated in neutrophils exposed to non-pathogenic bacteria (Yeramilli and Weissman, unpublished). The ATPase is also up-regulated in neutrophils by GM-CSF or phorbol myristic acid. Up-regulation of the ATPase is one of the mechanisms that may delay apoptosis in activated neutrophils. However a specific role for the ATP6G in inflammation remains to be established by more specific means."[9]
Gene ID: 534 is ATP6V1G2 ATPase H+ transporting V1 subunit G2 on 6p21.33: "This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of three V1 domain G subunit proteins. This gene had previous gene symbols of ATP6G and ATP6G2. Alternatively spliced transcript variants encoding different isoforms have been described. Read-through transcription also exists between this gene and the downstream DEAD (Asp-Glu-Ala-Asp) box polypeptide 39B (DDX39B) gene."[17]
NP_001191007.1 V-type proton ATPase subunit G 2 isoform c.[17]
NP_569730.1 V-type proton ATPase subunit G 2 isoform a.[17]
NP_612139.1 V-type proton ATPase subunit G 2 isoform b.[17]
Gene ID: 7916 is PRRC2A proline rich coiled-coil 2A aka G2; BAT2; D6S51; D6S51E on 6p21.33: "A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. These genes are all within the human major histocompatibility complex class III region. This gene has microsatellite repeats which are associated with the age-at-onset of insulin-dependent diabetes mellitus (IDDM) and possibly thought to be involved with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. This gene is also a candidate gene for the development of rheumatoid arthritis. Two transcript variants encoding the same protein have been found for this gene."[18]
NP_004629.3 protein PRRC2A: "Transcript Variant: This variant (2) represents the longer transcript. Variants 1 and 2 both encode the same protein."[18]
NP_542417.2 protein PRRC2A: "Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 2. Variants 1 and 2 both encode the same protein."[18]
Gene ID: 7917 is BAG6 BAG cochaperone 6 aka G3; BAT3 on 6p21.33: "This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene."[19]
NP_001092004.1 large proline-rich protein BAG6 isoform b: "Transcript Variant: This variant (4) differs in the 5' UTR and utilizes an alternative in-frame splice site in the 5' coding region, compared to variant 1. Variants 2, 3, and 4 encode the same isoform (b), which is 6 aa shorter than isoform a."[19]
NP_001186626.1 large proline-rich protein BAG6 isoform c: "Transcript Variant: This variant (5) differs in the 5' UTR and lacks three alternate in-frame segments compared to variant 1. The resulting isoform (c) has the same N- and C-termini but is shorter compared to isoform a."[19]
NP_001186627.1 large proline-rich protein BAG6 isoform d: "Transcript Variant: This variant (6) differs in the 5' UTR and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (d) has the same N- and C-termini but is shorter compared to isoform a."[19]
NP_542433.1 large proline-rich protein BAG6 isoform b: "Transcript Variant: This variant (2) differs in the 5' UTR and utilizes an alternative in-frame splice site in the 5' coding region, compared to variant 1. Variants 2, 3, and 4 encode the same isoform (b), which is 6 aa shorter than isoform a."[19]
NP_542434.1 large proline-rich protein BAG6 isoform b: "Transcript Variant: This variant (3) utilizes an alternative in-frame splice site in the 5' coding region, compared to variant 1. Variants 2, 3, and 4 encode the same isoform (b), which is 6 aa shorter than isoform a."[19]
Gene ID: 7918 is GPANK1 G-patch domain and ankyrin repeats 1 aka G5; BAT4, on 6p21.33: "This gene is located in a cluster of HLA-B-associated transcripts, which is included in the human major histocompatability complex III region. This gene encodes a protein which is thought to play a role in immunity. Multiple alternatively spliced variants, encoding the same protein, have been identified."[20]
NP_001186166.1 G patch domain and ankyrin repeat-containing protein 1: "Transcript Variant: This variant (1) represents the longest transcript."[20]
NP_001186167.1 G patch domain and ankyrin repeat-containing protein 1: "Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein."[20]
NP_001186168.1 G patch domain and ankyrin repeat-containing protein 1: "Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein."[20]
NP_001186169.1 G patch domain and ankyrin repeat-containing protein 1: "Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein."[20]
NP_149417.1 G patch domain and ankyrin repeat-containing protein 1: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein."[20]
Gene ID: 7919 is DDX39B DExD-box helicase 39B aka BAT1 on 6p21.33: "This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and it also plays an important role in mRNA export from the nucleus to the cytoplasm. This gene belongs to a cluster of genes localized in the vicinity of the genes encoding tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on both chromosomes 6 and 11. Read-through transcription also occurs between this gene and the upstream ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) gene."[21]
NP_004631.1 spliceosome RNA helicase DDX39B: "Transcript Variant: This variant (1) represents the longest transcript. Both variants 1 and 2 encode the same protein."[21]
NP_542165.1 spliceosome RNA helicase DDX39B: "Transcript Variant: This variant (2) uses an alternative splice site in the 5' UTR, compared to variant 1. Both variants 1 and 2 encode the same protein."[21]
Gene ID: 7920 is ABHD16A abhydrolase domain containing 16A, phospholipase, aka BAT5 on 6p21.33: "A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. The protein encoded by this gene is thought to be involved in some aspects of immunity. Alternatively spliced transcript variants have been described."[22]
NP_001170986.1 phosphatidylserine lipase ABHD16A isoform b: "Transcript Variant: This variant (2) differs in the 5' UTR and has multiple coding region differences, compared to variant 1. These differences cause translation initiation at an alternate AUG and result in an isoform (b) with a shorter, distinct N-terminus, compared to isoform 1."[22]
NP_066983.1 phosphatidylserine lipase ABHD16A isoform a: "Transcript Variant: This variant (1) encodes the longer isoform (a)."[22]
Class VI
"A cluster of genes for three related cytokines/cytokine receptors, tumor necrosis factor (TNF, formerly known as TNF-alpha or cachectin), lymphotoxin alpha (LTA), and lymphotoxin beta (LTB), lies in the Class IV region shortly before the most centromeric Class I related genes. TNF has been very extensively studied(5) and plays an important role in inflammation, bacterial(6) and viral infection,(7) tumor cachexia and the immune response. It is produced by a variety of cells including prominently monocytes, macrophages, and some T cell subsets."[9]
"LTB (also called TNF C) is a membrane bound molecule that forms a heterotrimer with LTA.(12) This LTA-LTB complex can then induce activation of NF kappa B in certain cell lines by binding with the LTB receptor, a member of the TNF receptor family.(13) (14) NF kappa B is a pleiotropic transcription factor capable of activating the expression of a great variety of genes critical for the Immunoin flammatory response.(14)"[9]
The region within the MHC class III gene cluster that contains genes for TNFs is also known as MHC class VI or the inflammatory region.[23]
Gene ID: 4049 is LTA lymphotoxin alpha on 6p21.33: "The encoded protein, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The protein is highly inducible, secreted, and forms heterotrimers with lymphotoxin-beta which anchor lymphotoxin-alpha to the cell surface. This protein also mediates a large variety of inflammatory, immunostimulatory, and antiviral responses, is involved in the formation of secondary lymphoid organs during development and plays a role in apoptosis. Genetic variations in this gene are associated with susceptibility to leprosy type 4, myocardial infarction, non-Hodgkin's lymphoma, and psoriatic arthritis. Alternatively spliced transcript variants have been observed for this gene."[24]
NP_000586.2 lymphotoxin-alpha precursor: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein."[24]
NP_001153212.1 lymphotoxin-alpha precursor: "Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein."[24]
Gene ID: 4050 is LTB lymphotoxin beta on 6p21.33: "Lymphotoxin beta is a type II membrane protein of the TNF family. It anchors lymphotoxin-alpha to the cell surface through heterotrimer formation. The predominant form on the lymphocyte surface is the lymphotoxin-alpha 1/beta 2 complex (e.g. 1 molecule alpha/2 molecules beta) and this complex is the primary ligand for the lymphotoxin-beta receptor. The minor complex is lymphotoxin-alpha 2/beta 1. LTB is an inducer of the inflammatory response system and involved in normal development of lymphoid tissue. Lymphotoxin-beta isoform b is unable to complex with lymphotoxin-alpha suggesting a function for lymphotoxin-beta which is independent of lympyhotoxin-alpha. Alternative splicing results in multiple transcript variants encoding different isoforms."[25]
NP_002332.1 lymphotoxin-beta isoform a: "Transcript Variant: This variant (1) represents the longer transcript, encodes the longer isoform (a), and can form the heterotrimeric complex with lymphotoxin-alpha."[25]
NP_033666.1 lymphotoxin-beta isoform b: "Transcript Variant: This splice variant (2) lacks an exon in the coding region, compared to variant 1. The encoded protein (isoform b) has a premature stop codon and lacks the majority of the extracellular domain, compared to isoform a. This loss impairs its ability to complex with lympytoxin-alpha."[25]
Gene ID: 7124 is TNF tumor necrosis factor on 6p21.33: "This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine."[26]
ATP-binding cassette (ABC) transporters
Gene ID: 23 is ABCF1 ATP binding cassette subfamily F member 1, on 6p21.33: "The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the GCN20 subfamily. Unlike other members of the superfamily, this protein lacks the transmembrane domains which are characteristic of most ABC transporters. This protein may be regulated by tumor necrosis factor-alpha and play a role in enhancement of protein synthesis and the inflammation process."[27] No immunoglobulins.[27]
NP_001020262.1 ATP-binding cassette sub-family F member 1 isoform a: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a)."[27]
NP_001081.1 ATP-binding cassette sub-family F member 1 isoform b: "Transcript Variant: This variant (2) lacks an alternate in-frame exon, compared to variant 1. The resulting protein (isoform b) is shorter than isoform a."[27]
Gene ID: 6890 is TAP1 transporter 1, ATP binding cassette subfamily B member aka transporter, ATP-binding cassette, major histocompatibility complex, 1 on 6p21.32: "The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Two transcript variants encoding different isoforms have been found for this gene."[28] No immunoglobulins.[28]
NP_000584.3 antigen peptide transporter 1 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."[28]
NP_001278951.1 antigen peptide transporter 1 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1."[28]
Gene ID: 6891 is TAP2 transporter 2, ATP binding cassette subfamily B member on 6p21.32: "The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. This gene is located 7 kb telomeric to gene family member ABCB2. The protein encoded by this gene is involved in antigen presentation. This protein forms a heterodimer with ABCB2 in order to transport peptides from the cytoplasm to the endoplasmic reticulum. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Alternative splicing of this gene produces products which differ in peptide selectivity and level of restoration of surface expression of MHC class I molecules."[29] No immunoglobulins.[29]
NP_000535.3 antigen peptide transporter 2 isoform 1: "Transcript Variant: This variant (1, B allele) represents the longer transcript and encodes the longest isoform (1). An allele (variant 1, A allele) exists in which a single nt change creates an internal stop codon, leading to a protein that is 17 aa shorter at the C-terminus."[29]
NP_001276972.1 antigen peptide transporter 2 isoform 3: "Transcript Variant: This variant (1, A allele) differs at 3 nt positions compared to variant 1, B allele. The resulting isoform (3) is shorter at the C-terminus compared to isoform 1."[29]
NP_061313.2 antigen peptide transporter 2 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding region compared to variant 1. The resulting isoform (2) is shorter and has a distinct C-terminus compared to isoform 1."[29]
Gene ID: 3096 is HIVEP1 HIVEP zinc finger 1 aka major histocompatibility complex binding protein 1 on 6p24.1: "This gene encodes a transcription factor belonging to the ZAS family, members of which are large proteins that contain a ZAS domain - a modular protein structure consisting of a pair of C2H2 zinc fingers with an acidic-rich region and a serine/threonine-rich sequence. These proteins bind specifically to the DNA sequence motif, GGGACTTTCC, found in the enhancer elements of several viral promoters, including human immunodeficiency virus (HIV), and to related sequences found in the enhancer elements of a number of cellular promoters. This protein binds to this sequence motif, suggesting a role in the transcriptional regulation of both viral and cellular genes."[30]
In addition to the DNA binding sequences listed above, the transcription factors that can open up and attach through the local epigenome need to be known and specified.
↑NCBI (2 February 2016). "Conserved Protein Domain Family cl11960: Ig Superfamily". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 22 May 2020.
↑NCBI (5 August 2015). "Conserved Protein Domain Family pfam13895: Ig_2". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 24 May 2020.
↑NCBI (16 January 2013). "Conserved Protein Domain Family smart00410: IG_like". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 24 May 2020.
↑RefSeq (July 2008). "TNF tumor necrosis factor [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 6 April 2020.