ZNF469 explained

Zinc finger protein 469 is a protein that in humans is encoded by the ZNF469 gene.^[1]

Function

This gene encodes a zinc-finger protein. Low-percent homology to certain collagens suggests that it may function as a transcription factor or extra-nuclear regulator factor for the synthesis or organization of collagen fibers. Mutations in this gene cause brittle cornea syndrome.^[1]

Clinical significance

Mutations in ZNF469 are associated to keratoconus.^[2] as well as a type of Ehlers-Danlos syndrome called brittle cornea syndrome.

Further reading

• Vitart V, Bencić G, Hayward C, Skunca Herman J, Huffman J, Campbell S, Bućan K, Navarro P, Gunjaca G, Marin J, Zgaga L, Kolcić I, Polasek O, Kirin M, Hastie ND, Wilson JF, Rudan I, Campbell H, Vatavuk Z, Fleck B, Wright A . New loci associated with central cornea thickness include COL5A1, AKAP13 and AVGR8 . Hum. Mol. Genet. . 19 . 21 . 4304–11 . 2010 . 20719862 . 10.1093/hmg/ddq349 . free .
• Christensen AE, Knappskog PM, Midtbø M, Gjesdal CG, Mengel-From J, Morling N, Rødahl E, Boman H . Brittle cornea syndrome associated with a missense mutation in the zinc-finger 469 gene . Invest. Ophthalmol. Vis. Sci. . 51 . 1 . 47–52 . 2010 . 19661234 . 10.1167/iovs.09-4251 . free .
• Lu Y, Dimasi DP, Hysi PG, Hewitt AW, Burdon KP, Toh T, Ruddle JB, Li YJ, Mitchell P, Healey PR, Montgomery GW, Hansell N, Spector TD, Martin NG, Young TL, Hammond CJ, Macgregor S, Craig JE, Mackey DA . Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness . PLOS Genet. . 6 . 5 . e1000947 . 2010 . 20485516 . 2869325 . 10.1371/journal.pgen.1000947 . free .
• Burkitt Wright EM, Spencer HL, Daly SB, Manson FD, Zeef LA, Urquhart J, Zoppi N, Bonshek R, Tosounidis I, Mohan M, Madden C, Dodds A, Chandler KE, Banka S, Au L, Clayton-Smith J, Khan N, Biesecker LG, Wilson M, Rohrbach M, Colombi M, Giunta C, Black GC . Mutations in PRDM5 in brittle cornea syndrome identify a pathway regulating extracellular matrix development and maintenance . Am. J. Hum. Genet. . 88 . 6 . 767–77 . 2011 . 21664999 . 3113239 . 10.1016/j.ajhg.2011.05.007 .
• Khan AO, Aldahmesh MA, Alkuraya FS . Brittle cornea without clinically-evident extraocular findings in an adult harboring a novel homozygous ZNF469 mutation . Ophthalmic Genet. . 33 . 4 . 257–9 . 2012 . 22486320 . 10.3109/13816810.2012.670362 . 38585727 . free .
• Abu A, Frydman M, Marek D, Pras E, Nir U, Reznik-Wolf H, Pras E . Deleterious mutations in the Zinc-Finger 469 gene cause brittle cornea syndrome . Am. J. Hum. Genet. . 82 . 5 . 1217–22 . 2008 . 18452888 . 2427192 . 10.1016/j.ajhg.2008.04.001 .
• Hoehn R, Zeller T, Verhoeven VJ, Grus F, Adler M, Wolfs RC, Uitterlinden AG, Castagne R, Schillert A, Klaver CC, Pfeiffer N, Mirshahi A . Population-based meta-analysis in Caucasians confirms association with COL5A1 and ZNF469 but not COL8A2 with central corneal thickness . Hum. Genet. . 131 . 11 . 1783–93 . 2012 . 22814818 . 10.1007/s00439-012-1201-3 . 17779513 .
• Khan AO, Aldahmesh MA, Mohamed JN, Alkuraya FS . Blue sclera with and without corneal fragility (brittle cornea syndrome) in a consanguineous family harboring ZNF469 mutation (p.E1392X) . Arch. Ophthalmol. . 128 . 10 . 1376–9 . 2010 . 20938016 . 10.1001/archophthalmol.2010.238 . free .

Notes and References

1. Web site: Entrez Gene: Zinc finger protein 469 . 2014-08-07 .
2. Vincent AL, Jordan CA, Cadzow MJ, Merriman TR, McGhee CN . Mutations in the zinc finger protein gene, ZNF469, contribute to the pathogenesis of keratoconus . Invest. Ophthalmol. Vis. Sci. . 55. 9. 5629–35. 2014 . 25097247 . 10.1167/iovs.14-14532 . free .