WDR35

Cilia effects upon perturbation of WDR35

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-3.92) PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Human ciliopathy phenotype:

Short rib-polydactyly syndrome, Verma-Naumoff type; short rib-polydactyly syndrome, Majewski type

Ciliopathy associations

• Cranioectodermal Dysplasia (Sensenbrenner)
• Ellis-van Creveld Syndrome
• Retinal Dystrophy/Degeneration
• Short-Rib Thoracic Dysplasia
• Skeletal Ciliopathy
• Weyers Acrofacial Dysostosis

References: PMID:20817137, PMID:22486404, PMID:17935248, PMID:26691894, PMID:21473986, PMID:24027799, PMID:24123776, PMID:38161384, PMID:35875935, PMID:35281231, PMID:33517396, PMID:25914204, PMID:26691894, PMID:33369054, PMID:32804427, PMID:26792575, PMID:22486404, PMID:33421337, PMID:29134781, PMID:40445021, PMID:33606107, PMID:32007091, PMID:36249524, PMID:38531627, PMID:29458881, PMID:28857138, PMID:39877340, PMID:28400947, PMID:22791528, PMID:26075268

Subcellular localization

centrosome

References: PMID:22987818, PMID:30570184

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• Signaling (Hedgehog, GPCRs, ion channels)

Function

IFT121. IFT complex A component, endogenous WDR35 localizes to cilia and centrosomes throughout the developing embryo and human and mouse fibroblasts lacking the protein fail to produce cilia. Human and mouse homozygouse mutations in WDR35 cause ciliopathy short-rib polydactyly syndrome (22987818). Heterozygous mutations shown to cause cranioectodermal dysplasia-2. OMIM:613602. Interacts with RagA, mTORC1 activator (30570184)