COCH

cochlin

Basic information

Region (hg38): 14:30874514-30895065

Previous symbols: [ "DFNA31", "DFNA9" ]

Links

ENSG00000100473

∙ NCBI:1690 ∙ OMIM:603196 ∙ HGNC:2180 ∙ Uniprot:O43405 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AD
autosomal dominant nonsyndromic hearing loss 9 (Strong), mode of inheritance: AD
hearing loss, autosomal recessive 110 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 110	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language developmen	Audiologic/Otolaryngologic	8817345; 9806553; 10400989; 14512963; 16261627; 18312449; 19161137; 20447147; 21046548; 21052762; 21774451; 22610276; 22931125; 29449721

ClinVar

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

not provided (7 variants)
Autosomal dominant nonsyndromic hearing loss 9 (6 variants)
Hereditary hearing loss and deafness (2 variants)
Rare genetic deafness (2 variants)
Bilateral sensorineural hearing impairment (1 variants)
Nonsyndromic genetic hearing loss (1 variants)
Hearing loss, autosomal recessive 110 (1 variants)
Hearing impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COCH gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.

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			3 clinvar	24 clinvar	5 clinvar	32
missense	7 clinvar	7 clinvar	97 clinvar	5 clinvar	4 clinvar	120
nonsense	1 clinvar	4 clinvar	2 clinvar			7
start loss						0
frameshift	3 clinvar		1 clinvar			4
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	11	12	103	29	9

Highest pathogenic variant AF is 0.0000131394

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COCH	protein_coding	protein_coding	ENST00000396618	11	20552

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.24e-7	0.946	125687	0	61	125748	0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.676	264	297	0.890	0.0000148	3612
Missense in Polyphen		99	112.74	0.87812		1481
Synonymous	-0.900	118	106	1.11	0.00000536	1088
Loss of Function	1.90	15	25.3	0.593	0.00000143	284

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000535	0.000535
Ashkenazi Jewish	0.000595	0.000595
East Asian	0.000870	0.000870
Finnish	0.00	0.00
European (Non-Finnish)	0.000151	0.000149
Middle Eastern	0.000870	0.000870
South Asian	0.000261	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Plays a role in the control of cell shape and motility in the trabecular meshwork. {ECO:0000269|PubMed:21886777}.;
Disease: DISEASE: Deafness, autosomal dominant, 9 (DFNA9) [MIM:601369]: A form of non-syndromic hearing loss characterized by onset in the fourth or fifth decade of life and initially involves the high frequencies. Hearing loss is progressive and usually complete by the sixth decade. In addition to cochlear involvement, DFNA9 patients also exhibit a spectrum of vestibular dysfunctions. Penetrance of the vestibular symptoms is often incomplete, and some patients are minimally affected, whereas others suffer from severe balance disturbances and episodes of vertigo. Affected individuals have mucopolysaccharide depositions in the channels of the cochlear and vestibular nerves. These depositions apparently cause strangulation and degeneration of dendritic fibers. {ECO:0000269|PubMed:10400989, ECO:0000269|PubMed:11295836, ECO:0000269|PubMed:12928864, ECO:0000269|PubMed:14512963, ECO:0000269|PubMed:16835921, ECO:0000269|PubMed:17561763, ECO:0000269|PubMed:18312449, ECO:0000269|PubMed:22610276, ECO:0000269|PubMed:22931125, ECO:0000269|PubMed:23993205, ECO:0000269|PubMed:25388789, ECO:0000269|PubMed:9806553, ECO:0000269|PubMed:9931344}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.132

Intolerance Scores

loftool: 0.238
rvis_EVS: 0.29
rvis_percentile_EVS: 71.5

Haploinsufficiency Scores

pHI: 0.533
hipred: Y
hipred_score: 0.501
ghis: 0.427

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.545

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Coch
Phenotype: normal phenotype; hearing/vestibular/ear phenotype;

Gene ontology

Biological process: growth plate cartilage chondrocyte morphogenesis;sensory perception of sound;regulation of cell shape;defense response to bacterium;positive regulation of innate immune response
Cellular component: extracellular space;extracellular matrix;collagen-containing extracellular matrix
Molecular function: protein binding;collagen binding