GeneBe

CEP78

protein-coding

centrosomal protein 78

Gene summary

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]

Previous symbols:
  • C9orf81

MANE transcript

NM_001330691.3

Inheritance

AR

ClinVar variants

P:82U:336B:127

Top phenotype

Cone rod dystrophy and hearing loss 1

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr9:78,236,062-78,279,690

External References & Databases

Ensembl (ENSG00000148019)NCBI Gene (84131)OMIM (617110)HGNC:25740GenCCUniProt (Q5JTW2)AlphaFoldClinVar (CEP78)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~43.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Usher syndrome type 3SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016485

Submitter: Orphanet

cone-rod dystrophy and hearing loss 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020778

Submitter: Labcorp Genetics (formerly Invitae)

cone-rod dystrophy and hearing lossDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014980

Submitter: G2P

cone-rod dystrophy and hearing lossSTRONG

Inheritance Pattern: Unknown

Disease ID:MONDO:0014980

Submitter: ClinGen

cone-rod dystrophy and hearing loss 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020778

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Cone rod dystrophy and hearing loss 1AR

Manifestation: Audiologic/Otolaryngologic; Ophthalmologic

Intervention: Audiologic/Otolaryngologic

Rationale: The condition can involve early-onset hearing impairment, and early recognition and treatment may improve outcomes, including speech and language development

Refs: 27588451; 27588452; 27627988; 31999394Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CEP78 variants in ClinVar

13 Conditions Cataloged
not providedTotal: 583
Inborn genetic diseasesTotal: 113
CEP78-related disorderTotal: 85
not specifiedTotal: 83
Cone-rod dystrophy and hearing loss 1Total: 36
Retinal dystrophyTotal: 17
Cone-rod dystrophyTotal: 4
Cone-rod dystrophy and hearing lossTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001330691.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
4
clinvar
100
clinvar
2
clinvar
 106
missense
6
clinvar
319
clinvar
23
clinvar
 348
nonsense
7
clinvar
8
clinvar
1
clinvar
 16
start loss
2
clinvar
 2
frameshift
26
clinvar
19
clinvar
2
clinvar
 47
splice donor/acceptor (+/-2bp)
4
clinvar
12
clinvar
8
clinvar
2
clinvar
 26
Total37453361252545

Highest pathogenic variant AF is 0.00020851793

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001330691.3RefSeqNP_001317620.117MANE Select
ENST00000643273.2EnsemblENSP00000496423.217MANE Select
NM_001098802.3RefSeqNP_001092272.116Standard
NM_001330693.3RefSeqNP_001317622.116Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Regulation of PLK1 Activity at G2/M Transition
  • Recruitment of mitotic centrosome proteins and complexes
  • Loss of Nlp from mitotic centrosomes
  • Loss of proteins required for interphase microtubule organization from the centrosome
  • Centrosome maturation

Biological Process

  • G2/M transition of mitotic cell cycle
  • regulation of G2/M transition of mitotic cell cycle
  • cilium organization
  • ciliary basal body-plasma membrane docking

Cellular Component

  • centrosome
  • centriole
  • cytosol
  • ciliary basal body

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000376597
Coding exons
16
Length
43629
Individuals with no LoFs
124582
Homozygous LoFs
0
Heterozygous LoFs
57
Defined
124639
p
0.000229
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.5803833521.090.00001714665
Missense (PolyPhen)180168.631.06742291
Synonymous1.711031280.8070.000006291378
Loss of Function1.482230.90.7130.00000138433

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000260.00026rare
Latino/Admixed American0.000360.00035rare
Ashkenazi Jewish0.000320.00030rare
East Asian0.000420.00039rare
Finnish0.000480.00046rare
European (Non-Finnish)0.000170.00016rare
South Asian0.000110.000098rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: May be required for efficient PLK4 centrosomal localization and PLK4-induced overduplication of centrioles (PubMed:27246242). May play a role in cilium biogenesis (PubMed:27588451). {ECO:0000269|PubMed:27246242, ECO:0000269|PubMed:27588451}.;
Disease
DISEASE: Cone-rod dystrophy and hearing loss (CRDHL) [MIM:617236]: An autosomal recessive disease defined by the association of progressive cone-rod dystrophy with sensorineural hearing loss. Cone-rod dystrophy is characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:27588451, ECO:0000269|PubMed:27588452, ECO:0000269|PubMed:27627988}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.111

Intolerance Scores

LoFtool
0.980
RVIS EVS
-0.09
RVIS percentile EVS
47.06

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.560

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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