8fh3

Structural highlights

Disease

WDR35_HUMAN Short rib-polydactyly syndrome, Verma-Naumoff type;Short rib-polydactyly syndrome type 5;Cranioectodermal dysplasia. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. WDR35 mutations cause short rib-polydactyly syndrome through impaired cilia formation. Primary fibroblasts from SRTD7 patients lacking WDR35 fail to produce cilia (PubMed:21473986).^[1] The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. SRTD7/20 can be caused by co-occurrence of WDR35 variant p.Trp311Leu and INTU p.Gln276Ter. One such patient has been reported.^[2]

Function

WDR35_HUMAN As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in ciliogenesis and ciliary protein trafficking (PubMed:21473986, PubMed:28400947, PubMed:29220510). May promote CASP3 activation and TNF-stimulated apoptosis.^{[3] [4] [5] [6]}

References

1. ↑ Mill P, Lockhart PJ, Fitzpatrick E, Mountford HS, Hall EA, Reijns MA, Keighren M, Bahlo M, Bromhead CJ, Budd P, Aftimos S, Delatycki MB, Savarirayan R, Jackson IJ, Amor DJ. Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis. Am J Hum Genet. 2011 Apr 8;88(4):508-15. PMID:21473986 doi:10.1016/j.ajhg.2011.03.015
2. ↑ Toriyama M, Lee C, Taylor SP, Duran I, Cohn DH, Bruel AL, Tabler JM, Drew K, Kelly MR, Kim S, Park TJ, Braun DA, Pierquin G, Biver A, Wagner K, Malfroot A, Panigrahi I, Franco B, Al-Lami HA, Yeung Y, Choi YJ, Duffourd Y, Faivre L, Rivière JB, Chen J, Liu KJ, Marcotte EM, Hildebrandt F, Thauvin-Robinet C, Krakow D, Jackson PK, Wallingford JB. The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery. Nat Genet. 2016 Jun;48(6):648-56. PMID:27158779 doi:10.1038/ng.3558
3. ↑ Feng GG, Li C, Huang L, Tsunekawa K, Sato Y, Fujiwara Y, Komatsu T, Honda T, Fan JH, Goto H, Koide T, Hasegawa T, Ishikawa N. Naofen, a novel WD40-repeat protein, mediates spontaneous and tumor necrosis factor-induced apoptosis. Biochem Biophys Res Commun. 2010 Mar 26;394(1):153-7. PMID:20193664 doi:10.1016/j.bbrc.2010.02.133
4. ↑ Mill P, Lockhart PJ, Fitzpatrick E, Mountford HS, Hall EA, Reijns MA, Keighren M, Bahlo M, Bromhead CJ, Budd P, Aftimos S, Delatycki MB, Savarirayan R, Jackson IJ, Amor DJ. Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis. Am J Hum Genet. 2011 Apr 8;88(4):508-15. PMID:21473986 doi:10.1016/j.ajhg.2011.03.015
5. ↑ Duran I, Taylor SP, Zhang W, Martin J, Qureshi F, Jacques SM, Wallerstein R, Lachman RS, Nickerson DA, Bamshad M, Cohn DH, Krakow D. Mutations in IFT-A satellite core component genes IFT43 and IFT121 produce short rib polydactyly syndrome with distinctive campomelia. Cilia. 2017 Apr 10;6:7. doi: 10.1186/s13630-017-0051-y. eCollection 2017. PMID:28400947 doi:http://dx.doi.org/10.1186/s13630-017-0051-y
6. ↑ Takahara M, Katoh Y, Nakamura K, Hirano T, Sugawa M, Tsurumi Y, Nakayama K. Ciliopathy-associated mutations of IFT122 impair ciliary protein trafficking but not ciliogenesis. Hum Mol Genet. 2018 Feb 1;27(3):516-528. PMID:29220510 doi:10.1093/hmg/ddx421