CEP164

Cilia effects upon perturbation of CEP164

Cilia number / % ciliated:

Decreased cilia number

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-6.71) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Phenotypes

Mouse phenotype:

preweaning lethality, complete penetrance Mesodermal-specific Cep164 deletion: severe bone defects, complete cilia loss in osteoblasts, increased gamma-H2AX-positive cells. Chondrocyte-specific deletion: no overt skeletal abnormalities.

Human ciliopathy phenotype:

Senior-Loken syndrome; nephronophthisis 15; ciliopathy

Ciliopathy associations

• Joubert Syndrome
• Nephronophthisis
• Senior-Løken Syndrome

References: PMID:22863007, PMID:34995479, PMID:36063381, PMID:37324592, PMID:39612644, PMID:28125082

Subcellular localization

basal body, centrosome, cytosol, nucleus, transition zone

References: PMID:41005307, PMID:17954613, PMID:23253480, PMID:24982133, PMID:23150559, PMID:32367404

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Protein processing & maturation
• Ciliary membrane

Function

Assembly of primary cilia and promotes vesicular docking and trafficking that initiates cilia membrane biogenesis (17954613, 23253480). CEP164 promotes accumulation of GTP-Rab8 at the centrosome, providing a molecular link connecting the M-centriole to components of the machinery that initiate ciliary membrane biogenesis (23253480). Recruitment of active tau tubulin kinase 2 (TTBK2) to centrioles, leading to removal of CP110 and recruitment of intraflagellar transport proteins (24982133). Mutations in CEP164 are related to nephronophthisis and Joubert syndrome, it may may facilitate the docking of the INPP5E–PDE6D complex to the centrosomal distal appendage/transition fiber (23150559). Mutations also reported in a BBS/PCD case (32367404). Osteoblast-specific CEP164 deletion causes severe bone defects and complete loss of cilia in osteoblasts. Cell-type specific: chondrocyte deletion does not cause overt skeletal abnormalities. CEP164 has both ciliary and non-ciliary (DNA damage response) functions in osteoblasts.