CEP104

Chr 1AR

centrosomal protein 104

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

NCBI Gene: 9731 ENSG00000116198 UniProt: O60308 OMIM: 616690

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 OMIM 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 OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.742 OMIM phenotypes

Clinical Summary— CEP104

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Gene-Disease Validity (ClinGen)

ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

51 unique Pathogenic / Likely Pathogenic· 212 VUS of 657 total submissions

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GeneReview available — CEP104

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 3.05

OE 0.54 (0.40–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.44Z-score

OE missense 0.95 (0.88–1.02)

503 obs / 531.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.40–0.74)

0≤0.351.4

Missense OE?0.95 (0.88–1.02)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 28 / 51.7Missense obs/exp: 503 / 531.8Syn Z: 1.65

ClinVar Variant Classifications

657 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20

Likely Pathogenic31

VUS212

Likely Benign221

Benign131

Conflicting19

Pathogenic

Likely Pathogenic

212

VUS

221

Likely Benign

131

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	18	0	2	0	20
Likely Pathogenic	31	0	0	0	31
VUS	2	201	8	1	212
Likely Benign	1	17	115	88	221
Benign	2	4	120	5	131
Conflicting	—				19
Total	54	222	245	94	634

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

90 pathogenic / likely-pathogenic (of 103) ClinVar copy-number / structural variants overlap CEP104 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →