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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 27.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
ENST00000216361.9	ENSP00000216361.5	11	-	-
ENST00000396618.9	ENSP00000379862.3	11	yes	-
ENST00000460581.6	ENSP00000451713.1	8	-	-
ENST00000468826.2	ENSP00000452284.1	6	-	-

Phenotypes

GenCC

Source: genCC

• 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
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD

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 (219 variants)
• Autosomal_dominant_nonsyndromic_hearing_loss_9 (54 variants)
• Inborn_genetic_diseases (53 variants)
• not_specified (28 variants)
• COCH-related_disorder (19 variants)
• Hearing_loss,_autosomal_recessive_110 (9 variants)
• Nonsyndromic_genetic_hearing_loss (7 variants)
• Hearing_impairment (4 variants)
• Rare_genetic_deafness (3 variants)
• Hereditary_hearing_loss_and_deafness (3 variants)
• Monogenic_hearing_loss (1 variants)
• Bilateral_sensorineural_hearing_impairment (1 variants)
• Prelingual_sensorineural_hearing_impairment (1 variants)
• Usher_syndrome (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: NM_000004086.3. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	33	4	41
missense	10	13	139	13	2	177
nonsense	2	4	3			9
start loss						0
frameshift	8		2			10
splice donor/acceptor (+/-2bp)		1	1			2
Total	20	18	149	46	6

Highest pathogenic variant AF is 0.00005328152

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
		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

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

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