Autosomal dominant nonsyndromic hearing loss 9

Summary

Autosomal dominant nonsyndromic hearing loss 9 (MONDO:0011058) is a disease caused by COCH (GenCC Strong), with 2 cohort genes and 6 clinical trials.

At a glance

• Causal gene: COCH (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 73
• Clinical trials: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant nonsyndromic hearing loss 9
Mondo ID	MONDO:0011058
MeSH	C563335
OMIM	601369
DOID	DOID:0110593
UMLS	C1832425
MedGen	371327
GARD	0018105
Is cancer (heuristic)	no

Also known as: autosomal dominant deafness 9 · autosomal dominant nonsyndromic deafness 9 · autosomal dominant nonsyndromic deafness caused by mutation in COCH · autosomal dominant nonsyndromic deafness type 9 · COCH autosomal dominant nonsyndromic deafness · deafness, autosomal dominant 9 · deafness, autosomal dominant type 9 · DFNA9

Data availability: 73 ClinVar variants · 1 ClinGen variant curation · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant nonsyndromic hearing loss › autosomal dominant nonsyndromic hearing loss 9

Related subtypes (75): autosomal dominant nonsyndromic hearing loss 1, autosomal dominant nonsyndromic hearing loss 2A, autosomal dominant nonsyndromic hearing loss 4A, autosomal dominant nonsyndromic hearing loss 6, autosomal dominant nonsyndromic hearing loss 5, autosomal dominant nonsyndromic hearing loss 10, autosomal dominant nonsyndromic hearing loss 11, autosomal dominant nonsyndromic hearing loss 7, autosomal dominant nonsyndromic hearing loss 12, autosomal dominant nonsyndromic hearing loss 3A, autosomal dominant nonsyndromic hearing loss 13, autosomal dominant nonsyndromic hearing loss 15, autosomal dominant nonsyndromic hearing loss 17, autosomal dominant nonsyndromic hearing loss 16, autosomal dominant nonsyndromic hearing loss 20, autosomal dominant nonsyndromic hearing loss 23, autosomal dominant nonsyndromic hearing loss 25, autosomal dominant nonsyndromic hearing loss 18, autosomal dominant nonsyndromic hearing loss 24, autosomal dominant nonsyndromic hearing loss 22, autosomal dominant nonsyndromic hearing loss 30, autosomal dominant nonsyndromic hearing loss 36, autosomal dominant nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 44, autosomal dominant nonsyndromic hearing loss 48, autosomal dominant nonsyndromic hearing loss 41, autosomal dominant nonsyndromic hearing loss 49, autosomal dominant nonsyndromic hearing loss 43, autosomal dominant nonsyndromic hearing loss 28, autosomal dominant nonsyndromic hearing loss 31, autosomal dominant nonsyndromic hearing loss 47, autosomal dominant auditory neuropathy 1, autosomal dominant nonsyndromic hearing loss 53, autosomal dominant nonsyndromic hearing loss 27, autosomal dominant nonsyndromic hearing loss 59, autosomal dominant nonsyndromic hearing loss 3B, autosomal dominant nonsyndromic hearing loss 2B, autosomal dominant nonsyndromic hearing loss 50, autosomal dominant nonsyndromic hearing loss 51, autosomal dominant nonsyndromic hearing loss 64, autosomal dominant nonsyndromic hearing loss 33, autosomal dominant nonsyndromic hearing loss 4B, autosomal dominant nonsyndromic hearing loss 56, autosomal dominant nonsyndromic hearing loss 54, autosomal dominant nonsyndromic hearing loss 58, autosomal dominant nonsyndromic hearing loss 65, autosomal dominant nonsyndromic hearing loss 67, autosomal dominant nonsyndromic hearing loss 40, autosomal dominant nonsyndromic hearing loss 69, autosomal dominant nonsyndromic hearing loss 68, autosomal dominant nonsyndromic hearing loss 70, autosomal dominant nonsyndromic hearing loss 66, hearing loss, autosomal dominant 74, hearing loss, autosomal dominant 77, hearing loss, autosomal dominant 81, hearing loss, autosomal dominant 82, hearing loss, autosomal dominant 83, hearing loss, autosomal dominant 84, hearing loss, autosomal dominant 80, hearing loss, autosomal dominant 37, hearing loss, autosomal dominant 75, hearing loss, autosomal dominant 76, hearing loss, autosomal dominant 71, hearing loss, autosomal dominant 72, hearing loss, autosomal dominant 73, hearing loss, autosomal dominant 34, with or without inflammation, hearing loss, autosomal dominant 78, hearing loss, autosomal dominant 79, hearing loss, autosomal dominant 85, hearing loss, autosomal dominant 86, hearing loss, autosomal dominant 87, hearing loss, autosomal dominant 88, hearing loss, autosomal dominant 89, hearing loss, autosomal dominant 90, autosomal dominant nonsyndromic hearing loss 91

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

73 retrieved; paginated sample, class counts are floors:

25 uncertain significance, 11 benign, 10 conflicting classifications of pathogenicity, 9 pathogenic, 7 likely pathogenic, 6 likely benign, 4 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
236036	NM_004086.3(COCH):c.1159C>T (p.Leu387Phe)	COCH	Pathogenic	no assertion criteria provided
2736106	NM_004086.3(COCH):c.362T>C (p.Phe121Ser)	COCH	Pathogenic	criteria provided, multiple submitters, no conflicts
6608	NM_004086.3(COCH):c.197T>G (p.Val66Gly)	COCH	Pathogenic	no assertion criteria provided
6610	NM_004086.3(COCH):c.349T>C (p.Trp117Arg)	COCH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6611	NM_004086.3(COCH):c.151C>T (p.Pro51Ser)	COCH	Pathogenic	reviewed by expert panel
6612	NM_004086.3(COCH):c.326T>A (p.Ile109Asn)	COCH	Pathogenic	criteria provided, single submitter
6614	NM_004086.3(COCH):c.1625G>T (p.Cys542Phe)	COCH	Pathogenic	criteria provided, multiple submitters, no conflicts
1174533	NM_004086.3(COCH):c.341T>C (p.Leu114Pro)	COCH-AS1	Pathogenic	criteria provided, single submitter
6615	NM_004086.3(COCH):c.1625G>A (p.Cys542Tyr)	COCH-AS1	Pathogenic	criteria provided, single submitter
6616	NM_004086.3(COCH):c.1535T>C (p.Met512Thr)	COCH-AS1	Pathogenic	no assertion criteria provided
3601050	NM_004086.3(COCH):c.1412T>G (p.Val471Gly)	COCH	Likely pathogenic	criteria provided, single submitter
3601051	NM_004086.3(COCH):c.1547C>A (p.Pro516Gln)	COCH	Likely pathogenic	criteria provided, single submitter
3601053	NM_004086.3(COCH):c.152C>A (p.Pro51Gln)	COCH	Likely pathogenic	criteria provided, single submitter
3601054	NM_004086.3(COCH):c.340C>G (p.Leu114Val)	COCH	Likely pathogenic	criteria provided, single submitter
3620741	NM_004086.3(COCH):c.260G>A (p.Gly87Glu)	COCH	Likely pathogenic	reviewed by expert panel
431458	NM_004086.3(COCH):c.292C>T (p.Arg98Ter)	COCH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3601052	NM_004086.3(COCH):c.1547C>G (p.Pro516Arg)	COCH-AS1	Likely pathogenic	criteria provided, single submitter
228523	NM_004086.3(COCH):c.1348A>G (p.Ile450Val)	COCH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
228525	NM_004086.3(COCH):c.971G>A (p.Arg324Gln)	COCH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
313002	NM_004086.3(COCH):c.961-8C>T	COCH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523013	NM_004086.3(COCH):c.1150C>T (p.Arg384Cys)	COCH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178988	NM_004086.3(COCH):c.263G>T (p.Gly88Val)	COCH-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197227	NM_004086.3(COCH):c.239+5G>A	COCH-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
500137	NM_004086.3(COCH):c.272G>A (p.Arg91Gln)	COCH-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
6609	NM_004086.3(COCH):c.263G>A (p.Gly88Glu)	COCH-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
881628	NM_004086.3(COCH):c.1436A>T (p.Tyr479Phe)	COCH-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
882736	NM_004086.3(COCH):c.108C>T (p.Thr36=)	COCH-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028194	NM_004086.3(COCH):c.329A>G (p.Gln110Arg)	COCH	Uncertain significance	criteria provided, multiple submitters, no conflicts
2430251	NM_004086.3(COCH):c.366_371del (p.Val123_Thr124del)	COCH	Uncertain significance	criteria provided, single submitter
313006	NM_004086.3(COCH):c.*10T>A	COCH	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
COCH	Definitive	Autosomal dominant	nonsyndromic genetic hearing loss	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COCH	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COCH	HGNC:2180	ENSG00000100473	O43405	Cochlin	gencc,clinvar
COCH-AS1	HGNC:58454	ENSG00000258525		COCH antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COCH	Cochlin	Plays a role in the control of cell shape and motility in the trabecular meshwork.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COCH	Other/Unknown	no		VWF_A, LCCL, vWFA_dom_sf
COCH-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
saphenous vein	1
skeletal muscle tissue of biceps brachii	1
nucleus accumbens	1
sperm	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COCH	272	broad	marker	buccal mucosa cell, saphenous vein, skeletal muscle tissue of biceps brachii
COCH-AS1	152		yes	sural nerve, sperm, nucleus accumbens

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COCH	1,226
COCH-AS1	0

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COCH	O43405	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of cell shape	1	123.0×	0.010	COCH
sensory perception of sound	1	100.9×	0.010	COCH

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COCH	0	0
COCH-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	COCH, COCH-AS1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
COCH	0	—
COCH-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03716908	Not specified	RECRUITING	Genotype-phenotype Correlation Study of Presymptomatic and Symptomatic DFNA9 Patients
NCT04070937	Not specified	RECRUITING	Correlation of Radiological Lesions With Vestibular Function in Patients With Bilateral Vestibulopathy
NCT03707756	Not specified	WITHDRAWN	Systematic Review of Phenotypical Characteristics of P51S COCH Mutation
NCT04066270	Not specified	UNKNOWN	Inventory of Radiological and Vestibular Function in Cochlear Implant Candidates
NCT04331015	Not specified	COMPLETED	Artificial Intelligence in Diagnosis of DFNA9
NCT07091071	Not specified	COMPLETED	Evaluation of the CochSyn Device in Clinical Practice