CCDC141

Subcellular localization

Nucleoplasm

References: PMID:39047937

Functional category

• Metabolism
• Trafficking (BBSome
• small GTPases
• vesicular transport
• ATPases)
• Ciliary assembly/disassembly
• Cilia–cytoskeleton/adhesion links

Function

The knockdown of ccdc141 in zebrafish disrupts early LR signaling pathways, cilia function, and Kupffer's vesicle formation. Unlike ccdc141-knockdown embryos exhibiting aberrant LR patterns, ccdc141-null mutants show no apparent abnormality, suggesting a genetic compensation response effect. In parallel, we observe a marked reduction in α-tubulin acetylation levels in the ccdc141 crispants. The treatment with histone deacetylase (HDAC) inhibitors, particularly the HDAC6 inhibitor, rescues the ccdc141 crispant phenotypes. Furthermore, exome analysis of 70 patients with laterality defects reveals an increased burden of CCDC141 mutations, with in-vivo studies verifying the pathogenicity of the patient mutation CCDC141-R123G. Our findings highlight the critical role of ccdc141 in ciliogenesis and demonstrate that CCDC141 mutations lead to abnormal LR patterns, identifying it as a candidate gene for laterality defects(39047937).