CEP78

Chr 9AR

centrosomal protein 78

Also known as: C9orf81, CRDHL, IP63

NCBI Gene: 84131ENSG00000148019UniProt: Q5JTW2

This gene encodes a centrosomal protein that is both required for the regulation of centrosome-related events during the cell cycle, and required for ciliogenesis. The encoded protein has an N-terminal leucine-rich repeat (LRR) domain with six consecutive LRR repeats, and a C-terminal coiled-coil domain. It interacts with the N-terminal catalytic domain of polo-like kinase 4 (PLK4) and colocalizes with PLK4 to the distal end of the centriole. Naturally occurring mutations in this gene cause defects in primary cilia that result in retinal degeneration and sensorineural hearing loss which are associated with cone-rod degeneration disease as well as Usher syndrome. Low expression of this gene is associated with poor prognosis of colorectal cancer patients. [provided by RefSeq, Mar 2017]

Primary Disease Associations & Inheritance

Cone-rod dystrophy and hearing lossMIM #617236
AR
703
ClinVar variants
47
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CEP78
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
47 Pathogenic / Likely Pathogenic· 205 VUS of 703 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.02LOEUF
pLI 0.000
Z-score 1.48
OE 0.71 (0.51–1.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.58Z-score
OE missense 1.09 (1.00–1.18)
383 obs / 352.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.71 (0.51–1.02)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.09 (1.00–1.18)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.81
0≤1.21.6
LoF obs/exp: 22 / 30.9Missense obs/exp: 383 / 352.4Syn Z: 1.71

ClinVar Variant Classifications

703 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic8
VUS205
Likely Benign130
Benign4
39
Pathogenic
8
Likely Pathogenic
205
VUS
130
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
24
0
15
0
39
Likely Pathogenic
6
0
2
0
8
VUS
0
187
15
3
205
Likely Benign
1
3
58
68
130
Benign
0
0
4
0
4
Total311909471386

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

View in ClinVar →

Protein Context — Lollipop Plot

CEP78 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CEP78-related cone-rod dystrophy and hearing loss

definitive
ARLoss Of FunctionAbsent Gene Product
EyeEar
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cone-rod dystrophy and hearing loss

MIM #617236

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Loss-of-function mutations in CEP78 cause male infertility in humans and mice.
Zhang X et al.·Sci Adv
2022
A novel frameshift variant in CEP78 associated with nonsyndromic retinitis pigmentosa, and a review of CEP78-related phenotypes.
Lähteenoja L et al.·Ophthalmic Genet
2022Review
Exploring the diverse clinical and variant spectrum of CEP78-associated syndrome: Novel pathogenic variants identified in a case series.
Zhai Y et al.·Am J Med Genet A
2024Cohort
Functional characterization of the first missense variant in CEP78, a founder allele associated with cone-rod dystrophy, hearing loss, and reduced male fertility.
Ascari G et al.·Hum Mutat
2020Case report
A Novel CEP78 Variant Presenting as Cone Dystrophy and Hearing Loss.
Faruque PR et al.·Ophthalmic Surg Lasers Imaging Retina
2024Case report
Significance of CEP78 and WDR62 gene expressions in differentiated thyroid carcinoma: Possible predictors of lateral lymph node metastasis.
Hammad MO et al.·Asia Pac J Clin Oncol
2019
CEP78 is mutated in a distinct type of Usher syndrome.
Fu Q et al.·J Med Genet
2017
Low expression of centrosomal protein 78 (CEP78) is associated with poor prognosis of colorectal cancer patients.
Zhang M et al.·Chin J Cancer
2016Cohort
Bi-allelic Truncating Mutations in CEP78, Encoding Centrosomal Protein 78, Cause Cone-Rod Degeneration with Sensorineural Hearing Loss.
Namburi P et al.·Am J Hum Genet
2016
Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.
Nikopoulos K et al.·Am J Hum Genet
2016Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools