IRF6
From Wikipedia, the free encyclopedia
Interferon regulatory factor 6 also known as IRF6 is a protein that in humans is encoded by the IRF6 gene.[1]
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[edit] Function
This gene encodes a member of the interferon regulatory transcription factor (IRF) family. Family members share a highly-conserved N-terminal helix-turn-helix DNA-binding domain and a less conserved C-terminal protein-binding domain.[2]
The function of IRF6 is related to the formation of connective tissue, for example that of the palate.[3] This gene encodes a member of the interferon regulatory transcription factor (IRF) family.
[edit] Pathology
A mutation of the IRF6 gene can lead to van der Woude syndrome[4] or the related popliteal pterygium syndrome.[5] These disorders are caused by mutations in the IRF6 gene and some of the phenotypic heterogeneity is due to different types of IRF6 mutations.[1] One explanation for this phenotypic variation between syndromes is based on a differential impact on the structure of the dimerized mutant proteins. VWS mutations appear to result in haploinsufficiency while PPS mutations may be dominant negative in nature.[6] The spectrum of mutations in VWS and PPS has been recently summarized.[7] IRF6 has been shown to play a critical role in keratinocyte development.[8][9] A role for IRF6 in the common forms of cleft lip and palate has also been demonstrated[10] and may explain ~20% of cases of cleft lip only.[11]
[edit] See also
[edit] References
- ^ a b Kondo S, Schutte BC, Richardson RJ, Bjork BC, Knight AS, Watanabe Y, Howard E, de Lima RL, Daack-Hirsch S, Sander A, McDonald-McGinn DM, Zackai EH, Lammer EJ, Aylsworth AS, Ardinger HH, Lidral AC, Pober BR, Moreno L, Arcos-Burgos M, Valencia C, Houdayer C, Bahuau M, Moretti-Ferreira D, Richieri-Costa A, Dixon MJ, Murray JC (October 2002). "Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes". Nat. Genet. 32 (2): 285–9. doi:10.1038/ng985. PMID 12219090.
- ^ "Entrez Gene: IRF6". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3664.
- ^ Blanton SH, Cortez A, Stal S, Mulliken JB, Finnell RH, Hecht JT (September 2005). "Variation in IRF6 contributes to nonsyndromic cleft lip and palate". Am. J. Med. Genet. A 137A (3): 259–62. doi:10.1002/ajmg.a.30887. PMID 16096995.
- ^ Van der Woude, A (June 1954). "Fistula labii inferioris congenita and its association with cleft lip and palate". Am. J. Hum. Genet. 6 (2): 244–56. PMC 1716548. PMID 13158329. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1716548.
- ^ Gorlin RJ, Sedano HO, Cervenka J (February 1968). "Popliteal pterygium syndrome . A syndrome comprising cleft lip-palate, popliteal and intercrural pterygia, digital and genital anomalies". Pediatrics 41 (2): 503–9. PMID 4384166.
- ^ Little HJ, Rorick NK, Su LI, Baldock C, Malhotra S, Jowitt T, Gakhar L, Subramanian R, Schutte BC, Dixon MJ, Shore P (November 2008). "Mis-sense mutations that cause Van der Woude syndrome and popliteal pterygium syndrome affect the DNA-binding and transcriptional activation functions of IRF6". Hum. Mol. Genet. 18 (3): 535–45. doi:10.1093/hmg/ddn381. PMC 2638798. PMID 19036739. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2638798.
- ^ de Lima RL, Hoper SA, Ghassibe M, et al. (April 2009). "Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome". Genet. Med. 11 (4): 241–7. doi:10.1097/GIM.0b013e318197a49a. PMC 2789395. PMID 19282774. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2789395.
- ^ Richardson RJ, Dixon J, Malhotra S, Hardman MJ, Knowles L, Boot-Handford RP, Shore P, Whitmarsh A, Dixon MJ (November 2006). "Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch". Nat. Genet. 38 (11): 1329–34. doi:10.1038/ng1894. PMID 17041603.
- ^ Ingraham CR, Kinoshita A, Kondo S, Yang B, Sajan S, Trout KJ, Malik MI, Dunnwald M, Goudy SL, Lovett M, Murray JC, Schutte BC (November 2006). "Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6)". Nat. Genet. 38 (11): 1335–40. doi:10.1038/ng1903. PMC 2082114. PMID 17041601. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2082114.
- ^ Zucchero TM, Cooper ME, Maher BS, Daack-Hirsch S, Nepomuceno B, Ribeiro L, Caprau D, Christensen K, Suzuki Y, Machida J, Natsume N, Yoshiura K, Vieira AR, Orioli IM, Castilla EE, Moreno L, Arcos-Burgos M, Lidral AC, Field LL, Liu YE, Ray A, Goldstein TH, Schultz RE, Shi M, Johnson MK, Kondo S, Schutte BC, Marazita ML, Murray JC (August 2004). "Interferon regulatory factor 6 (IRF6) gene variants and the risk of isolated cleft lip or palate". N. Engl. J. Med. 351 (8): 769–80. doi:10.1056/NEJMoa032909. PMID 15317890.
- ^ Rahimov F, Marazita ML, Visel A, Cooper ME, Hitchler MJ, Rubini M, Domann FE, Govil M, Christensen K, Bille C, Melbye M, Jugessur A, Lie RT, Wilcox AJ, Fitzpatrick DR, Green ED, Mossey PA, Little J, Steegers-Theunissen RP, Pennacchio LA, Schutte BC, Murray JC (November 2008). "Disruption of an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip". Nat. Genet. 40 (11): 1341–7. doi:10.1038/ng.242. PMC 2691688. PMID 18836445. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2691688.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
