Autosomal dominant nonsyndromic hearing loss 11

Summary

Autosomal dominant nonsyndromic hearing loss 11 (MONDO:0011032) is a disease caused by MYO7A (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MYO7A (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 537

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant nonsyndromic hearing loss 11
Mondo ID	MONDO:0011032
MeSH	C563353
OMIM	601317
DOID	DOID:0110543
UMLS	C1832475
MedGen	331297
GARD	0018104
Is cancer (heuristic)	no

Also known as: autosomal dominant deafness 11 · autosomal dominant nonsyndromic deafness 11 · autosomal dominant nonsyndromic deafness caused by mutation in MYO7A · autosomal dominant nonsyndromic deafness type 11 · deafness, autosomal dominant 11 · deafness, autosomal dominant type 11 · DFNA11 · MYO7A autosomal dominant nonsyndromic deafness

Data availability: 537 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 dominant disease › autosomal dominant nonsyndromic hearing loss › autosomal dominant nonsyndromic hearing loss 11

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 9, 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

537 retrieved; paginated sample, class counts are floors:

177 conflicting classifications of pathogenicity, 146 uncertain significance, 64 pathogenic/likely pathogenic, 45 pathogenic, 45 benign, 31 benign/likely benign, 25 likely pathogenic, 4 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1071057	NM_000260.4(MYO7A):c.5428A>T (p.Lys1810Ter)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
1076122	NM_000260.4(MYO7A):c.6126C>G (p.Tyr2042Ter)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
11851	NM_000260.4(MYO7A):c.634C>T (p.Arg212Cys)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11857	NM_000260.4(MYO7A):c.2662_2670del (p.Lys888_Lys890del)	MYO7A	Pathogenic	no assertion criteria provided
11860	NM_000260.4(MYO7A):c.1996C>T (p.Arg666Ter)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
11863	NM_000260.4(MYO7A):c.1373A>T (p.Asn458Ile)	MYO7A	Pathogenic	criteria provided, single submitter
11864	NM_000260.4(MYO7A):c.5143GAG[1] (p.Glu1716del)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1297516	NM_000260.4(MYO7A):c.3289C>T (p.Gln1097Ter)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
1323320	NM_000260.4(MYO7A):c.2569C>T (p.Gln857Ter)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1333565	NM_000260.4(MYO7A):c.2557C>T (p.Arg853Cys)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1393609	NM_000260.4(MYO7A):c.3829del (p.Ala1277fs)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452979	NM_000260.4(MYO7A):c.2513G>A (p.Trp838Ter)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
1454925	NM_000260.4(MYO7A):c.6228_6232del (p.Asp2076fs)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
164693	NM_000260.4(MYO7A):c.3892G>A (p.Gly1298Arg)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
177723	NM_000260.4(MYO7A):c.3979G>A (p.Glu1327Lys)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
177733	NM_000260.4(MYO7A):c.2863G>A (p.Gly955Ser)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
178495	NM_000260.4(MYO7A):c.5899C>T (p.Arg1967Ter)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
178993	NM_000260.4(MYO7A):c.689C>T (p.Ala230Val)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
179479	NM_000260.4(MYO7A):c.3503G>A (p.Arg1168Gln)	MYO7A	Pathogenic	reviewed by expert panel
1965262	NM_000260.4(MYO7A):c.604del (p.Ala202fs)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2137200	NM_000260.4(MYO7A):c.721C>G (p.Arg241Gly)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2137204	NM_000260.4(MYO7A):c.3109-2A>G	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
228280	NM_000260.4(MYO7A):c.2904G>A (p.Glu968=)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
242392	NM_000260.4(MYO7A):c.1969C>T (p.Arg657Trp)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2503091	NM_000260.4(MYO7A):c.5915G>A (p.Trp1972Ter)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2845671	NM_000260.4(MYO7A):c.5260C>T (p.Gln1754Ter)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
2915463	NM_000260.4(MYO7A):c.2187+2_2187+8del	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
29924	NM_000260.4(MYO7A):c.652G>A (p.Asp218Asn)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3004900	NM_000260.4(MYO7A):c.846dup (p.Met283fs)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382102	NM_000260.4(MYO7A):c.6479G>A (p.Trp2160Ter)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 4 · 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
MYO7A	Definitive	Autosomal dominant	nonsyndromic genetic hearing loss	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYO7A	Orphanet:231169	Usher syndrome type 1
MYO7A	Orphanet:231178	Usher syndrome type 2
MYO7A	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MYO7A	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
MYO7A	HGNC:7606	ENSG00000137474	Q13402	Unconventional myosin-VIIa	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYO7A	Unconventional myosin-VIIa	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)
MYO7A	Scaffold/PPI	no		IQ_motif_EF-hand-BS, FERM_domain, MyTH4_dom

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
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYO7A	186	broad	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYO7A	43

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYO7A	Q13402	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
The canonical retinoid cycle in rods (twilight vision)	1	519.1×	0.007	MYO7A
Sensory processing of sound	1	308.6×	0.007	MYO7A
Visual phototransduction	1	259.6×	0.007	MYO7A
Sensory processing of sound by outer hair cells of the cochlea	1	203.9×	0.007	MYO7A
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.007	MYO7A
Sensory Perception	1	95.2×	0.011	MYO7A

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
pigment granule transport	1	16852.0×	0.001	MYO7A
phagolysosome assembly	1	3370.4×	0.002	MYO7A
mechanoreceptor differentiation	1	3370.4×	0.002	MYO7A
equilibrioception	1	2407.4×	0.002	MYO7A
sensory perception of light stimulus	1	1872.4×	0.002	MYO7A
eye photoreceptor cell development	1	842.6×	0.003	MYO7A
auditory receptor cell stereocilium organization	1	842.6×	0.003	MYO7A
actin filament-based movement	1	802.5×	0.003	MYO7A
sensory organ development	1	674.1×	0.003	MYO7A
cochlea development	1	468.1×	0.004	MYO7A
lysosome organization	1	306.4×	0.005	MYO7A
actin filament organization	1	118.7×	0.012	MYO7A
intracellular protein localization	1	104.7×	0.012	MYO7A
sensory perception of sound	1	100.9×	0.012	MYO7A
endocytosis	1	95.2×	0.012	MYO7A
visual perception	1	79.5×	0.013	MYO7A
intracellular protein transport	1	64.8×	0.015	MYO7A

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
MYO7A	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	MYO7A

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)
MYO7A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.