CEP104

Chr 1

centrosomal protein 104

Also known as: CFAP256, GlyBP, JBTS25, KIAA0562, MRT77, ROC22

NCBI Gene: 9731 ENSG00000116198 UniProt: O60308

The encoded protein is required for ciliogenesis and maintains structural integrity at the ciliary tip, translocating from centriole tips to the elongating cilium during ciliary formation. Mutations cause autosomal recessive Joubert syndrome 25, characterized by distinctive mid-hindbrain and cerebellar malformation with oculomotor apraxia, irregular breathing, developmental delay, and ataxia, as well as intellectual developmental disorder. This gene shows low constraint against loss-of-function variants (LOEUF 0.743), consistent with its recessive inheritance pattern.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a centrosomal protein required for ciliogenesis and for ciliary tip structural integrity. The mammalian protein contains three amino-terminal hydrophobic domains, two glycosylation sites, four cysteine-rich motifs, and two regions with homology to the glutamate receptor ionotropic, NMDA 1 protein. During ciliogenesis, the encoded protein translocates from the distal tips of the centrioles to the tip of the elongating cilium. Knockdown of the protein in human retinal pigment cells results in severe defects in ciliogenesis with structural deformities at the ciliary tips. Allelic variants of this gene are associated with the autosomal-recessive disorder Joubert syndrome, which is characterized by a distinctive mid-hindbrain and cerebellar malformation, oculomotor apraxia, irregular breathing, developmental delay, and ataxia. [provided by RefSeq, Feb 2016]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtJoubert syndrome 25

UniProtIntellectual developmental disorder, autosomal recessive 77

Clinical highlights

Gene-disease validity (ClinGen)

ciliopathy · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.74

LOEUF

LOF

Mechanism· G2P

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GeneReview available — CEP104