DIAPH1: Difference between revisions

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== Function ==
== Function ==


This gene is a homolog of the Drosophila diaphanous gene and belongs to the protein family of the [[formin]]s, characterized by the formin homology 2 (FH2) domain. It has been linked to [[autosomal dominant]], fully penetrant, nonsyndromic sensorineural progressive low-frequency hearing loss. [[Actin]] polymerization involves proteins known to interact with diaphanous protein in ''[[Drosophila]]'' and [[mouse]]. It has therefore been speculated that this gene may have a role in the regulation of [[actin]] polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.<ref name="entrez" />
This gene is a [[Homology (biology)|homolog]] of the ''[[Drosophila]]'' diaphanous gene and belongs to the [[protein]] family of the [[formin]]s, characterized by the formin homology 2 (FH2) [[Protein domain|domain.]] It has been linked to [[autosomal dominant]], fully [[Penetrance|penetrant]], nonsyndromic low-frequency progressive [[sensorineural hearing loss]]. [[Actin]] [[polymerization]] involves proteins known to interact with diaphanous protein in ''Drosophila'' and [[mouse]]. It has therefore been speculated that this gene may have a role in the regulation of [[actin]] polymerization in [[Hair cell|hair cells]] of the [[inner ear]]. [[Alternative splicing|Alternatively spliced]] transcript variants encoding distinct [[Protein isoform|isoforms]] have been found for this gene.<ref name="entrez" />


== Interactions ==
== Interactions ==
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==Clinical significance==
==Clinical significance==


Mutations in this gene have been associated with [[wikt:macrothrombocytopenia|macrothrombocytopenia]] and hearing loss,<ref name=Stritt2016>{{cite journal | vauthors = Stritt S, Nurden P, Turro E, Greene D, Jansen SB, Westbury SK, Petersen R, Astle WJ, Marlin S, Bariana TK, Kostadima M, Lentaigne C, Maiwald S, Papadia S, Kelly AM, Stephens JC, Penkett CJ, Ashford S, Tuna S, Austin S, Bakchoul T, Collins P, Favier R, Lambert MP, Mathias M, Millar CM, Mapeta R, Perry DJ, Schulman S, Simeoni I, Thys C, Gomez K, Erber WN, Stirrups K, Rendon A, Bradley JR, van Geet C, Raymond FL, Laffan MA, Nurden AT, Nieswandt B, Richardson S, Freson K, Ouwehand WH, Mumford AD | display-authors = 6 | title = A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss | journal = Blood | volume = 127 | issue = 23 | pages = 2903–14 | date = June 2016 | pmid = 26912466 | doi = 10.1182/blood-2015-10-675629 }}</ref>  [[microcephaly]], blindness, and early onset seizures<ref name=Al-Maawali2016>{{cite journal | vauthors = Al-Maawali A, Barry BJ, Rajab A, El-Quessny M, Seman A, Coury SN, Barkovich AJ, Yang E, Walsh CA, Mochida GH, Stoler JM | display-authors = 6 | title = Novel loss-of-function variants in DIAPH1 associated with syndromic microcephaly, blindness, and early onset seizures | journal = American Journal of Medical Genetics. Part A | volume = 170A | issue = 2 | pages = 435–40 | date = February 2016 | pmid = 26463574 | pmc = 5315085 | doi = 10.1002/ajmg.a.37422 }}</ref>
[[Mutation|Mutations]] in this gene have been associated with [[wikt:macrothrombocytopenia|macrothrombocytopenia]] and hearing loss,<ref name=Stritt2016>{{cite journal | vauthors = Stritt S, Nurden P, Turro E, Greene D, Jansen SB, Westbury SK, Petersen R, Astle WJ, Marlin S, Bariana TK, Kostadima M, Lentaigne C, Maiwald S, Papadia S, Kelly AM, Stephens JC, Penkett CJ, Ashford S, Tuna S, Austin S, Bakchoul T, Collins P, Favier R, Lambert MP, Mathias M, Millar CM, Mapeta R, Perry DJ, Schulman S, Simeoni I, Thys C, Gomez K, Erber WN, Stirrups K, Rendon A, Bradley JR, van Geet C, Raymond FL, Laffan MA, Nurden AT, Nieswandt B, Richardson S, Freson K, Ouwehand WH, Mumford AD | display-authors = 6 | title = A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss | journal = Blood | volume = 127 | issue = 23 | pages = 2903–14 | date = June 2016 | pmid = 26912466 | doi = 10.1182/blood-2015-10-675629 }}</ref>  [[microcephaly]], blindness, and early onset seizures<ref name=Al-Maawali2016>{{cite journal | vauthors = Al-Maawali A, Barry BJ, Rajab A, El-Quessny M, Seman A, Coury SN, Barkovich AJ, Yang E, Walsh CA, Mochida GH, Stoler JM | display-authors = 6 | title = Novel loss-of-function variants in DIAPH1 associated with syndromic microcephaly, blindness, and early onset seizures | journal = American Journal of Medical Genetics. Part A | volume = 170A | issue = 2 | pages = 435–40 | date = February 2016 | pmid = 26463574 | pmc = 5315085 | doi = 10.1002/ajmg.a.37422 }}</ref>


Its actions on [[platlet]] formation appear to occur at the level of the [[megakaryocyte]] where it is involved in [[cytoskeleton]] formation.<ref name=Pan2014>{{cite journal | vauthors = Pan J, Lordier L, Meyran D, Rameau P, Lecluse Y, Kitchen-Goosen S, Badirou I, Mokrani H, Narumiya S, Alberts AS, Vainchenker W, Chang Y | display-authors = 6 | title = The formin DIAPH1 (mDia1) regulates megakaryocyte proplatelet formation by remodeling the actin and microtubule cytoskeletons | journal = Blood | volume = 124 | issue = 26 | pages = 3967–77 | year = 2014 | pmid = 25298036 | doi = 10.1182/blood-2013-12-544924 }}</ref>
Its actions on [[platelet]] formation appear to occur at the level of the [[megakaryocyte]] where it is involved in [[cytoskeleton]] formation.<ref name=Pan2014>{{cite journal | vauthors = Pan J, Lordier L, Meyran D, Rameau P, Lecluse Y, Kitchen-Goosen S, Badirou I, Mokrani H, Narumiya S, Alberts AS, Vainchenker W, Chang Y | display-authors = 6 | title = The formin DIAPH1 (mDia1) regulates megakaryocyte proplatelet formation by remodeling the actin and microtubule cytoskeletons | journal = Blood | volume = 124 | issue = 26 | pages = 3967–77 | year = 2014 | pmid = 25298036 | doi = 10.1182/blood-2013-12-544924 }}</ref>


== See also ==
== See also ==

Latest revision as of 16:26, 13 December 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Protein diaphanous homolog 1 is a protein that in humans is encoded by the DIAPH1 gene.[1][2][3]

Function

This gene is a homolog of the Drosophila diaphanous gene and belongs to the protein family of the formins, characterized by the formin homology 2 (FH2) domain. It has been linked to autosomal dominant, fully penetrant, nonsyndromic low-frequency progressive sensorineural hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[3]

Interactions

DIAPH1 has been shown to interact with RHOA.[4]

Clinical significance

Mutations in this gene have been associated with macrothrombocytopenia and hearing loss,[5] microcephaly, blindness, and early onset seizures[6]

Its actions on platelet formation appear to occur at the level of the megakaryocyte where it is involved in cytoskeleton formation.[7]

See also

References

  1. Lynch ED, Lee MK, Morrow JE, Welcsh PL, León PE, King MC (November 1997). "Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous". Science. 278 (5341): 1315–8. doi:10.1126/science.278.5341.1315. PMID 9360932.
  2. Leon PE, Raventos H, Lynch E, Morrow J, King MC (June 1992). "The gene for an inherited form of deafness maps to chromosome 5q31". Proceedings of the National Academy of Sciences of the United States of America. 89 (11): 5181–4. doi:10.1073/pnas.89.11.5181. PMC 49253. PMID 1350680.
  3. 3.0 3.1 "Entrez Gene: DIAPH1 diaphanous homolog 1 (Drosophila)".
  4. Riento K, Guasch RM, Garg R, Jin B, Ridley AJ (June 2003). "RhoE binds to ROCK I and inhibits downstream signaling". Molecular and Cellular Biology. 23 (12): 4219–29. doi:10.1128/MCB.23.12.4219-4229.2003. PMC 156133. PMID 12773565.
  5. Stritt S, Nurden P, Turro E, Greene D, Jansen SB, Westbury SK, et al. (June 2016). "A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss". Blood. 127 (23): 2903–14. doi:10.1182/blood-2015-10-675629. PMID 26912466.
  6. Al-Maawali A, Barry BJ, Rajab A, El-Quessny M, Seman A, Coury SN, et al. (February 2016). "Novel loss-of-function variants in DIAPH1 associated with syndromic microcephaly, blindness, and early onset seizures". American Journal of Medical Genetics. Part A. 170A (2): 435–40. doi:10.1002/ajmg.a.37422. PMC 5315085. PMID 26463574.
  7. Pan J, Lordier L, Meyran D, Rameau P, Lecluse Y, Kitchen-Goosen S, et al. (2014). "The formin DIAPH1 (mDia1) regulates megakaryocyte proplatelet formation by remodeling the actin and microtubule cytoskeletons". Blood. 124 (26): 3967–77. doi:10.1182/blood-2013-12-544924. PMID 25298036.

Further reading

External links