CEP78

centrosomal protein 78

Basic information

Region (hg38): 9:78236062-78279690

Previous symbols: [ "C9orf81" ]

Links

ENSG00000148019 ∙ NCBI:84131 ∙ OMIM:617110 ∙ HGNC:25740 ∙ Uniprot:Q5JTW2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cone-rod dystrophy and hearing loss 1 (Strong), mode of inheritance: AR
• cone-rod dystrophy and hearing loss 1 (Strong), mode of inheritance: AR
• cone-rod dystrophy and hearing loss 1 (Strong), mode of inheritance: AR
• Usher syndrome type 3 (Supportive), mode of inheritance: AR
• cone-rod dystrophy and hearing loss (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cone rod dystrophy and hearing loss 1	AR	Audiologic/Otolaryngologic	The condition can involve early-onset hearing impairment, and early recognition and treatment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Ophthalmologic	27588451; 27588452; 27627988; 31999394

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CEP78 gene.

• not provided (29 variants)
• Cone-rod dystrophy and hearing loss 1 (3 variants)
• Cone-rod dystrophy;Sensorineural hearing loss disorder (1 variants)
• Cone-rod dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CEP78 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	81	8	90
missense		2	252	7	2	263
nonsense	8	4	1			13
start loss			2			2
frameshift	20	5				25
inframe indel			5	1		6
splice donor/acceptor (+/-2bp)	1	6	1			8
splice region	1	1	13	21	5	41
non coding			4	47	28	79
Total	29	17	266	136	38

Highest pathogenic variant AF is 0.0000263

Variants in CEP78

This is a list of pathogenic ClinVar variants found in the CEP78 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-78236227-C-T			Benign (May 15, 2021)
9-78236351-A-T			Uncertain significance (Aug 30, 2023)
9-78236352-T-C			Uncertain significance (Apr 28, 2022)
9-78236361-C-T			Uncertain significance (Apr 05, 2022)
9-78236364-T-C			Uncertain significance (Aug 27, 2021)
9-78236372-C-T		Moyamoya angiopathy • CEP78-related disorder	Conflicting classifications of pathogenicity (Jul 20, 2024)
9-78236385-C-T		not specified • CEP78-related disorder	Benign (Jan 29, 2024)
9-78236389-G-A			Likely benign (Jul 08, 2022)
9-78236390-G-T			Uncertain significance (Jul 19, 2022)
9-78236391-ACTT-A			Likely benign (Jan 20, 2024)
9-78236395-C-T			Likely benign (Aug 26, 2020)
9-78236402-C-T			Uncertain significance (Jul 12, 2022)
9-78236404-C-T			Likely benign (Oct 13, 2022)
9-78236407-C-T			Likely benign (Nov 23, 2021)
9-78236408-G-A			Uncertain significance (Apr 28, 2022)
9-78236408-G-T			Pathogenic (Mar 25, 2020)
9-78236409-A-T			Uncertain significance (Aug 06, 2022)
9-78236409-AG-A			Pathogenic (Oct 24, 2022)
9-78236411-T-TACC		Retinal dystrophy	Uncertain significance (Jul 13, 2018)
9-78236414-C-T			Likely benign (Feb 14, 2023)
9-78236421-C-T			Uncertain significance (Aug 16, 2022)
9-78236422-G-A			Likely benign (Aug 21, 2022)
9-78236422-G-T			Likely benign (Aug 23, 2022)
9-78236423-C-G		Inborn genetic diseases	Uncertain significance (Jan 03, 2022)
9-78236424-T-C			Uncertain significance (Mar 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CEP78	protein_coding	protein_coding	ENST00000376597	16	43629

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.17e-12	0.611	124582	0	57	124639	0.000229

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.580	383	352	1.09	0.0000171	4665
Missense in Polyphen		180	168.63	1.0674		2291
Synonymous	1.71	103	128	0.807	0.00000629	1378
Loss of Function	1.48	22	30.9	0.713	0.00000138	433

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000624	0.000618
Ashkenazi Jewish	0.000317	0.000298
East Asian	0.000422	0.000389
Finnish	0.000477	0.000464
European (Non-Finnish)	0.000168	0.000159
Middle Eastern	0.000422	0.000389
South Asian	0.000105	0.0000980
Other	0.00	0.00

dbNSFP

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.
• Pathway: 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;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.980
• rvis_EVS: -0.09
• rvis_percentile_EVS: 47.06

Haploinsufficiency Scores

• pHI: 0.192
• hipred: N
• hipred_score: 0.144
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.560

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cep78

Gene ontology

• 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