Autosomal recessive nonsyndromic hearing loss 37

Summary

Autosomal recessive nonsyndromic hearing loss 37 (MONDO:0011912) is a disease caused by MYO6 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MYO6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 204

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 37
Mondo ID	MONDO:0011912
MeSH	C564331
OMIM	607821
DOID	DOID:0110495
UMLS	C1843028
MedGen	375076
GARD	0022605
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 37 · autosomal recessive nonsyndromic deafness 37 · autosomal recessive nonsyndromic deafness caused by mutation in MYO6 · autosomal recessive nonsyndromic deafness type 37 · autosomal recessive nonsyndromic hearing loss 37 · deafness, autosomal recessive 37 · deafness, autosomal recessive type 37 · DFNB37 · MYO6 autosomal recessive nonsyndromic deafness

Data availability: 204 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › hearing loss, autosomal recessive › autosomal recessive nonsyndromic hearing loss 37

Related subtypes (101): autosomal recessive nonsyndromic hearing loss 5, autosomal recessive nonsyndromic hearing loss 1A, autosomal recessive nonsyndromic hearing loss 2, autosomal recessive nonsyndromic hearing loss 3, autosomal recessive nonsyndromic hearing loss 4, autosomal recessive nonsyndromic hearing loss 6, autosomal recessive nonsyndromic hearing loss 7, autosomal recessive nonsyndromic hearing loss 9, autosomal recessive nonsyndromic hearing loss 8, autosomal recessive nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 15, autosomal recessive nonsyndromic hearing loss 18A, autosomal recessive nonsyndromic hearing loss 17, autosomal recessive nonsyndromic hearing loss 13, autosomal recessive nonsyndromic hearing loss 21, autosomal recessive nonsyndromic hearing loss 14, autosomal recessive nonsyndromic hearing loss 16, autosomal recessive nonsyndromic hearing loss 20, autosomal recessive nonsyndromic hearing loss 26, autosomal recessive nonsyndromic hearing loss 27, autosomal recessive nonsyndromic hearing loss 22, autosomal recessive nonsyndromic hearing loss 31, autosomal recessive nonsyndromic hearing loss 30, autosomal recessive nonsyndromic hearing loss 33, autosomal recessive nonsyndromic hearing loss 38, autosomal recessive nonsyndromic hearing loss 40, autosomal recessive nonsyndromic hearing loss 39, autosomal recessive nonsyndromic hearing loss 35, autosomal recessive nonsyndromic hearing loss 32, autosomal recessive nonsyndromic hearing loss 36, autosomal recessive nonsyndromic hearing loss 48, autosomal recessive nonsyndromic hearing loss 23, autosomal recessive nonsyndromic hearing loss 42, autosomal recessive nonsyndromic hearing loss 46, autosomal recessive nonsyndromic hearing loss 53, autosomal recessive nonsyndromic hearing loss 28, autosomal recessive nonsyndromic hearing loss 51, autosomal recessive nonsyndromic hearing loss 47, autosomal recessive nonsyndromic hearing loss 55, autosomal recessive nonsyndromic hearing loss 62, autosomal recessive nonsyndromic hearing loss 49, autosomal recessive nonsyndromic hearing loss 44, autosomal recessive nonsyndromic hearing loss 66, autosomal recessive nonsyndromic hearing loss 59, autosomal recessive nonsyndromic hearing loss 65, autosomal recessive nonsyndromic hearing loss 67, autosomal recessive nonsyndromic hearing loss 68, autosomal recessive nonsyndromic hearing loss 24, autosomal recessive nonsyndromic hearing loss 63, autosomal recessive nonsyndromic hearing loss 45, autosomal recessive nonsyndromic hearing loss 1B, autosomal recessive nonsyndromic hearing loss 71, autosomal recessive nonsyndromic hearing loss 77, autosomal recessive nonsyndromic hearing loss 25, autosomal recessive nonsyndromic hearing loss 79, autosomal recessive nonsyndromic hearing loss 84A, autosomal recessive nonsyndromic hearing loss 85, autosomal recessive nonsyndromic hearing loss 91, autosomal recessive nonsyndromic hearing loss 83, autosomal recessive nonsyndromic hearing loss 74, autosomal recessive nonsyndromic hearing loss 61, autosomal recessive nonsyndromic hearing loss 89, autosomal recessive nonsyndromic hearing loss 29, autosomal recessive nonsyndromic hearing loss 96, autosomal recessive nonsyndromic hearing loss 86, autosomal recessive nonsyndromic hearing loss 98, autosomal recessive nonsyndromic hearing loss 93, autosomal recessive nonsyndromic hearing loss 70, autosomal recessive nonsyndromic hearing loss 84B, autosomal recessive nonsyndromic hearing loss 18B, autosomal recessive nonsyndromic hearing loss 88, autosomal recessive nonsyndromic hearing loss 76, autosomal recessive nonsyndromic hearing loss 101, autosomal recessive nonsyndromic hearing loss 102, autosomal recessive nonsyndromic hearing loss 103, autosomal recessive nonsyndromic hearing loss 104, autosomal recessive nonsyndromic hearing loss 97, hearing loss, autosomal recessive 111, hearing loss, autosomal recessive 118, with cochlear aplasia, hearing loss, autosomal recessive 119, hearing loss, autosomal recessive 117, hearing loss, autosomal recessive 112, hearing loss, autosomal recessive 113, hearing loss, autosomal recessive 100, hearing loss, autosomal recessive 94, hearing loss, autosomal recessive 114, hearing loss, autosomal recessive 115, hearing loss, autosomal recessive 99, hearing loss, autosomal recessive 106, hearing loss, autosomal recessive 107, hearing loss, autosomal recessive 108, hearing loss, autosomal recessive 57, hearing loss, autosomal recessive 109, hearing loss, autosomal recessive 116, hearing loss, autosomal recessive 110, hearing loss, autosomal recessive 120, hearing loss, autosomal recessive 121, hearing loss, autosomal recessive 122, hearing loss, autosomal recessive 123, autosomal recessive nonsyndromic hearing loss 124, hearing loss, autosomal recessive 125

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

204 retrieved; paginated sample, class counts are floors:

96 uncertain significance, 64 conflicting classifications of pathogenicity, 18 benign, 10 benign/likely benign, 9 likely pathogenic, 3 pathogenic/likely pathogenic, 3 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1064988	NM_004999.4(MYO6):c.866_869del (p.Lys289fs)	MYO6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
164634	NM_004999.4(MYO6):c.826C>T (p.Arg276Ter)	MYO6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
228278	NM_004999.4(MYO6):c.2839C>T (p.Arg947Ter)	MYO6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3601440	NM_004999.4(MYO6):c.2366_2367del (p.Thr789fs)	MYO6	Pathogenic	criteria provided, single submitter
8578	NM_004999.4(MYO6):c.36dup (p.Thr13fs)	MYO6	Pathogenic	no assertion criteria provided
8579	NM_004999.4(MYO6):c.3496C>T (p.Arg1166Ter)	MYO6	Pathogenic	criteria provided, multiple submitters, no conflicts
1334126	NM_004999.4(MYO6):c.2777T>A (p.Leu926Gln)	MYO6	Likely pathogenic	criteria provided, single submitter
2429058	NM_004999.4(MYO6):c.2416+2T>C	MYO6	Likely pathogenic	criteria provided, single submitter
3382328	NM_004999.4(MYO6):c.3216_3219dup (p.Lys1074Ter)	MYO6	Likely pathogenic	criteria provided, single submitter
3601438	NM_004999.4(MYO6):c.117+1G>A	MYO6	Likely pathogenic	criteria provided, single submitter
3601439	NM_004999.4(MYO6):c.1223+2T>G	MYO6	Likely pathogenic	criteria provided, single submitter
3601441	NM_004999.4(MYO6):c.2522_2523del (p.Val841fs)	MYO6	Likely pathogenic	criteria provided, single submitter
390632	NM_004999.4(MYO6):c.817-1G>A	MYO6	Likely pathogenic	criteria provided, multiple submitters, no conflicts
402263	NM_004999.4(MYO6):c.897G>T (p.Glu299Asp)	MYO6	Likely pathogenic	criteria provided, single submitter
4076158	NM_004999.4(MYO6):c.2499_2500del (p.His833fs)	MYO6	Likely pathogenic	criteria provided, single submitter
164644	NM_004999.4(MYO6):c.3246T>C (p.Tyr1082=)	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178474	NM_004999.4(MYO6):c.2595C>T (p.Pro865=)	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178623	NM_004999.4(MYO6):c.1674+13A>G	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
180087	NM_004999.4(MYO6):c.441C>T (p.Ile147=)	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227673	NM_004999.4(MYO6):c.188-3T>C	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2499018	NM_004999.4(MYO6):c.2863C>T (p.Arg955Trp)	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
259604	NM_004999.4(MYO6):c.1144G>A (p.Asp382Asn)	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
259605	NM_004999.4(MYO6):c.2517T>C (p.Gly839=)	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357985	NM_004999.4(MYO6):c.-225G>C	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357987	NM_004999.4(MYO6):c.-49C>G	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357988	NM_004999.4(MYO6):c.262-12T>G	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357989	NM_004999.4(MYO6):c.262-9C>T	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357990	NM_004999.4(MYO6):c.564C>T (p.Leu188=)	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357994	NM_004999.4(MYO6):c.1180G>A (p.Val394Ile)	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357997	NM_004999.4(MYO6):c.2672C>T (p.Thr891Met)	MYO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 3 · 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
MYO6	Definitive	Autosomal dominant	autosomal dominant nonsyndromic hearing loss 22	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYO6	Orphanet:228012	Progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome
MYO6	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MYO6	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYO6	HGNC:7605	ENSG00000196586	Q9UM54	Unconventional myosin-VI	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYO6	Unconventional myosin-VI	Myosins are actin-based motor molecules with ATPase activity.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYO6	Scaffold/PPI	no		Myosin_head_motor_dom-like, SH3_Myosin, Myosin_S1_N

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
amniotic fluid	1
corpus callosum	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYO6	278	ubiquitous	marker	amniotic fluid, medial globus pallidus, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYO6	2,972

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYO6	Q9UM54	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Gap junction degradation	1	951.7×	0.005	MYO6
RHOBTB GTPase Cycle	1	815.7×	0.005	MYO6
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1	761.3×	0.005	MYO6
Trafficking of AMPA receptors	1	543.8×	0.005	MYO6
Gap junction trafficking and regulation	1	475.8×	0.005	MYO6
Gap junction trafficking	1	475.8×	0.005	MYO6
RHOBTB2 GTPase cycle	1	475.8×	0.005	MYO6
RHOBTB1 GTPase cycle	1	475.8×	0.005	MYO6
RHOU GTPase cycle	1	278.5×	0.007	MYO6
Neurotransmitter receptors and postsynaptic signal transmission	1	100.2×	0.018	MYO6
Transmission across Chemical Synapses	1	76.1×	0.021	MYO6
RHO GTPase cycle	1	60.1×	0.025	MYO6
Neuronal System	1	44.3×	0.031	MYO6
Membrane Trafficking	1	37.1×	0.032	MYO6
Vesicle-mediated transport	1	34.8×	0.032	MYO6
Signaling by Rho GTPases	1	34.2×	0.032	MYO6
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.032	MYO6
Signal Transduction	1	10.2×	0.098	MYO6

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 secretion	1	2808.7×	0.004	MYO6
inner ear auditory receptor cell differentiation	1	1203.7×	0.005	MYO6
actin filament-based movement	1	802.5×	0.005	MYO6
DNA damage response, signal transduction by p53 class mediator	1	358.6×	0.007	MYO6
inner ear morphogenesis	1	300.9×	0.007	MYO6
actin filament organization	1	118.7×	0.013	MYO6
intracellular protein localization	1	104.7×	0.013	MYO6
sensory perception of sound	1	100.9×	0.013	MYO6
endocytosis	1	95.2×	0.013	MYO6
response to xenobiotic stimulus	1	69.1×	0.015	MYO6
intracellular protein transport	1	64.8×	0.015	MYO6

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
MYO6	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	1	MYO6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYO6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.