CEP41

Chr 7AR

centrosomal protein 41

Also known as: JBTS15, TSGA14

NCBI Gene: 95681 ENSG00000106477 UniProt: Q9BYV8 OMIM: 610523

The protein is required for ciliogenesis and facilitates tubulin glutamylation in cilia by participating in the transport of TTLL6 tubulin polyglutamylase between the basal body and cilium. Mutations cause Joubert syndrome 15, an autosomal recessive ciliopathy characterized by neurological abnormalities. This gene shows high constraint against loss-of-function variants, indicating its critical role in normal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a centrosomal and microtubule-binding protein which is predicted to have two coiled-coil domains and a rhodanese domain. In human retinal pigment epithelial cells the protein localized to centrioles and cilia. Mutations in this gene have been associated with Joubert Syndrome 15; an autosomal recessive ciliopathy and neurological disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.921 OMIM phenotype

Clinical Summary— CEP41

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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

23 unique Pathogenic / Likely Pathogenic· 249 VUS of 485 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CEP41

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.92LOEUF

pLI 0.000

Z-score 1.83

OE 0.57 (0.36–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.35Z-score

OE missense 0.93 (0.83–1.05)

188 obs / 201.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.36–0.92)

0≤0.351.4

Missense OE?0.93 (0.83–1.05)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 12 / 21.1Missense obs/exp: 188 / 201.9Syn Z: 0.33

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCEP41-related Joubert syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7326th %ile

GOF

0.5171th %ile

LOF

0.3259th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

485 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic8

VUS249

Likely Benign148

Benign29

Conflicting15

Pathogenic

Likely Pathogenic

249

VUS

148

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	0	1	0	15
Likely Pathogenic	7	1	0	0	8
VUS	5	148	93	3	249
Likely Benign	1	5	87	55	148
Benign	0	0	29	0	29
Conflicting	—				15
Total	27	154	210	58	464

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap CEP41 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →