Common gamma chain

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The common gamma chainc) (or CD132), also known as interleukin-2 receptor subunit gamma or IL-2RG, is a cytokine receptor sub-unit that is common to the receptor complexes for at least six different interleukin receptors: IL-2, IL-4,[1] IL-7,[2] IL-9, IL-15[3] and interleukin-21 receptor. The γc glycoprotein is a member of the type I cytokine receptor family expressed on most lymphocyte (white blood cell) populations, and its gene is found on the X-chromosome of mammals.

This protein is located on the surface of immature blood-forming cells in bone marrow. One end of the protein resides outside the cell where it binds to cytokines and the other end of the protein resides in the interior of the cell where it transmits signals to the cell's nucleus. The common gamma chain partners with other proteins to direct blood-forming cells to form lymphocytes (a type of white blood cell). The receptor also directs the growth and maturation of lymphocyte subtypes: T cells, B cells, and natural killer cells. These cells kill viruses, make antibodies, and help regulate the entire immune system.


Cytokine receptor common subunit gamma also known as interleukin-2 receptor subunit gamma or IL-2RG is a protein that in humans is encoded by the IL2RG gene.[4] The human IL2RG gene is located on the long (q) arm of the X chromosome at position 13.1, from base pair 70,110,279 to base pair 70,114,423.

File:IL-7receptor and signaling.jpg
IL-7 receptor and signaling, common γ chain (blue) and IL-7 receptor-α (green)


The γc chain is an integral membrane protein that contains extracellular, transmembrane, and intracellular domains.


Lymphocytes expressing the common gamma chain can form functional receptors for these cytokine proteins, which transmit signals from one cell to another and direct programs of cellular differentiation.


The γc chain partners with other ligand-specific receptors to direct lymphocytes to respond to cytokines including IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.[5]


IL2RG has been shown to interact with Janus kinase 3.[6][7]

Clinical significance

X-linked severe combined immunodeficiency

X-linked severe combined immunodeficiency is caused by mutations in the IL2RG gene. More than 200 different mutations in the IL2RG gene have been identified in people with X-linked severe combined immunodeficiency (SCID).[8] Most of these mutations involve changes in one or a few nucleotides (DNA building blocks) in the gene. These changes lead to the production of a nonfunctional version of the common gamma chain protein[citation needed] or no production of protein.[9] Without the common gamma chain, important chemical signals are not relayed to the nucleus and lymphocytes cannot develop normally. A lack of functional mature lymphocytes disrupts the immune system's ability to protect the body from infection. Sufferers have no functional immunity and can die within months after birth without successful bone marrow transplantation or alternatively, isolation from exposure to pathogens. Without important developmental signals from IL-7 and IL-15, T-cell and NK cell populations respectively fail to develop.

Experiments in animal models have shown X-SCID to occur similarly in dogs, but not in mice.[10]


Alterations in the immune response are involved in pathogenesis of many neuropsychiatric disorders including schizophrenia. Distinct gene variants of a number of pro-inflammatory and chemotactic cytokines together with their receptors associate with this disorder. IL2RG represents an important signaling component of many interleukin receptors and so far, no data on the functional state of this receptor in schizophrenia have been reported. Over-expression of the IL2RG gene may be implicated in altered immune response in schizophrenia and contribute to the pathogenesis of this disorder.[11]


  1. Russell SM, Keegan AD, Harada N, Nakamura Y, Noguchi M, Leland P, Friedmann MC, Miyajima A, Puri RK, Paul WE (December 1993). "Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor" (Submitted manuscript). Science. 262 (5141): 1880–3. doi:10.1126/science.8266078. PMID 8266078.
  2. Noguchi M, Nakamura Y, Russell SM, Ziegler SF, Tsang M, Cao X, Leonard WJ (December 1993). "Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor" (Submitted manuscript). Science. 262 (5141): 1877–80. doi:10.1126/science.8266077. PMID 8266077.
  3. Giri JG, Kumaki S, Ahdieh M, Friend DJ, Loomis A, Shanebeck K, DuBose R, Cosman D, Park LS, Anderson DM (August 1995). "Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor". EMBO J. 14 (15): 3654–63. PMC 394440. PMID 7641685.
  4. Takeshita T, Asao H, Ohtani K, Ishii N, Kumaki S, Tanaka N, Munakata H, Nakamura M, Sugamura K (July 1992). "Cloning of the gamma chain of the human IL-2 receptor". Science. 257 (5068): 379–82. doi:10.1126/science.1631559. PMID 1631559.
  5. Asao H, Okuyama C, Kumaki S, Ishii N, Tsuchiya S, Foster D, Sugamura K (July 2001). "Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex". J. Immunol. 167 (1): 1–5. doi:10.4049/jimmunol.167.1.1. PMID 11418623.
  6. Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, Oishi I, Silvennoinen O, Witthuhn BA, Ihle JN (November 1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits". Science. 266 (5187): 1045–7. doi:10.1126/science.7973659. PMID 7973659.
  7. Russell SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, Berg M, McVicar DW, Witthuhn BA, Silvennoinen O (November 1994). "Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID" (Submitted manuscript). Science. 266 (5187): 1042–5. doi:10.1126/science.7973658. PMID 7973658.
  8. Vihinen M, Arredondo-Vega FX, Casanova JL, Etzioni A, Giliani S, Hammarström L, Hershfield MS, Heyworth PG, Hsu AP, Lähdesmäki A, Lappalainen I, Notarangelo LD, Puck JM, Reith W, Roos D, Schumacher RF, Schwarz K, Vezzoni P, Villa A, Väliaho J, Smith CI (2001). Primary immunodeficiency mutation databases. Adv. Genet. Advances in Genetics. 43. pp. 103–88. doi:10.1016/s0065-2660(01)43005-7. ISBN 9780120176434. PMID 11037300.
  9. Schmalstieg FC, Leonard WJ, Noguchi M, Berg M, Rudloff HE, Denney RM, Dave SK, Brooks EG, Goldman AS (March 1995). "Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency". J. Clin. Invest. 95 (3): 1169–73. doi:10.1172/JCI117765. PMC 441454. PMID 7883965.
  10. Henthorn PS, Somberg RL, Fimiani VM, Puck JM, Patterson DF, Felsburg PJ (September 1994). "IL-2R gamma gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease". Genomics. 23 (1): 69–74. doi:10.1006/geno.1994.1460. PMID 7829104.
  11. Ghazaryan H, Petrek M, Boyajyan A (2014). "Chronic schizophrenia is associated with over-expression of the interleukin-2 receptor gamma gene". Psychiatry Res. 217 (3): 158–62. doi:10.1016/j.psychres.2014.03.020. PMID 24713359.

Further reading

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