CEP295

Cilia effects upon perturbation of CEP295

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (1 screens)

• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-1.44) PMID:29459680

Phenotypes

Mouse phenotype:

abnormal embryo size, preweaning lethality, incomplete penetrance, decreased bone mineral content

Ciliopathy associations

• Seckel-like Syndrome

References: PMID:38154379

Subcellular localization

basal body, centrosome

References: PMID:27562453, PMID:38200359

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation

Function

Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest, and the loss of CEP295 causes extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells(PMID: 38154379). CEP295 is a conserved scaffold protein required to convert daughter centrioles into bona fide mother centrioles (PMID 27562453). Its Drosophila homolog Ana1 is required to maintain centrosomes; ana1 mutants lack stable centrosomes, and therefore the basal bodies that template cilia, and reduced Ana1 dosage produces abnormally short centrioles (PMID 38200359). Patient fibroblasts with bi-allelic CEP295 variants and CEP295-depleted RPE1 cells show a 3-fold reduction in ciliated cells, shorter cilia and an attenuated Hedgehog response; wild-type CEP295, but not the P562L mutant, rescues the centrosome and cilia defects. Bi-allelic CEP295 variants cause a Seckel-like syndrome with primary microcephaly, and a fetus with Meckel syndrome features was presumed homozygous for a CEP295 frameshift variant (PMID 38154379).