biostudies-literatureBizet AANIDDK NIH HHSHoward Hughes Medical Institute8666https://www.ebi.ac.uk/biostudies/studies/S-EPMC4617596biostudies-literatureUnknown6Ciliopathies are a large group of clinically and genetically heterogeneous disorders caused by defects in primary cilia. Here we identified mutations in TRAF3IP1 (TNF Receptor-Associated Factor Interacting Protein 1) in eight patients from five families with nephronophthisis (NPH) and retinal degeneration, two of the most common manifestations of ciliopathies. TRAF3IP1 encodes IFT54, a subunit of the IFT-B complex required for ciliogenesis. The identified mutations result in mild ciliary defects in patients but also reveal an unexpected role of IFT54 as a negative regulator of microtubule stability via MAP4 (microtubule-associated protein 4). Microtubule defects are associated with altered epithelialization/polarity in renal cells and with pronephric cysts and microphthalmia in zebrafish eNature communicationsMutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization.PMC4617596DK068306R01 DK053093R01 DK068306Becker-Heck ADubot PHildebrandt FRyan RGubler MCSaint-Mezard PSaunier SNitschke PBenmerah AFilhol EHalbritter JLinghu BDrummond IAWeber KSahel JAElshakhs NASPinson LSzustakowski JDSailer AWZarhrate MDelous MOakeley EJSalomon RAntignac CYang FBizet AAKrug PLasbennes MCBouwmeester TGarfa-Traore MSerluca FCassuto EChibout SLorentzen EfalseMutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization.Ciliopathies are a large group of clinically and genetically heterogeneous disorders caused by defects in primary cilia. Here we identified mutations in TRAF3IP1 (TNF Receptor-Associated Factor Interacting Protein 1) in eight patients from five families with nephronophthisis (NPH) and retinal degeneration, two of the most common manifestations of ciliopathies. TRAF3IP1 encodes IFT54, a subunit of the IFT-B complex required for ciliogenesis. The identified mutations result in mild ciliary defects in patients but also reveal an unexpected role of IFT54 as a negative regulator of microtubule stability via MAP4 (microtubule-associated protein 4). Microtubule defects are associated with altered epithelialization/polarity in renal cells and with pronephric cysts and microphthalmia in zebrafish e2015-01-01T00:00:00Z2015 Oct2026-05-03T00:29:19.757Z2019-03-27T02:00:37ZS-EPMC46175962648726810.1038/ncomms9666