Autosomal recessive nonsyndromic hearing loss 2

Summary

Autosomal recessive nonsyndromic hearing loss 2 (MONDO:0010807) is a disease caused by MYO7A (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MYO7A (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 793

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 2
Mondo ID	MONDO:0010807
MeSH	C564007
OMIM	600060
DOID	DOID:0110477
UMLS	C1838701
MedGen	325485
GARD	0022582
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 2 · autosomal recessive nonsyndromic deafness 2 · autosomal recessive nonsyndromic deafness caused by mutation in MYO7A · autosomal recessive nonsyndromic deafness type 2 · deafness, autosomal recessive 2 · deafness, autosomal recessive type 2 · DFNB2 · MYO7A autosomal recessive nonsyndromic deafness

Data availability: 793 ClinVar variants · 3 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 2

Related subtypes (101): autosomal recessive nonsyndromic hearing loss 5, autosomal recessive nonsyndromic hearing loss 1A, 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 37, 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

600 retrieved; paginated sample, class counts are floors:

156 conflicting classifications of pathogenicity, 124 uncertain significance, 103 pathogenic, 73 likely pathogenic, 68 pathogenic/likely pathogenic, 32 benign/likely benign, 28 benign, 16 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
424810	NM_000260.3(MYO7A):c.[1969C>T];[29T>C]		Pathogenic	no assertion criteria provided
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
11847	NM_000260.4(MYO7A):c.448C>T (p.Arg150Ter)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
11848	NM_000260.4(MYO7A):c.700C>T (p.Gln234Ter)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
11850	NM_000260.4(MYO7A):c.635G>A (p.Arg212His)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1185084	NM_000260.4(MYO7A):c.4972C>T (p.Gln1658Ter)	MYO7A	Pathogenic/Likely 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
1185130	NM_000260.4(MYO7A):c.1679A>G (p.Tyr560Cys)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11853	NM_000260.4(MYO7A):c.731G>C (p.Arg244Pro)	MYO7A	Pathogenic	criteria provided, single submitter
11855	NM_000260.4(MYO7A):c.3596dup (p.Cys1201fs)	MYO7A	Pathogenic	no assertion criteria provided
11856	NM_000260.4(MYO7A):c.1797G>A (p.Met599Ile)	MYO7A	Pathogenic	no assertion criteria provided
1185626	NM_000260.4(MYO7A):c.1091dup (p.Asp365fs)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
11858	NM_000260.4(MYO7A):c.1884C>A (p.Cys628Ter)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
11859	NM_000260.4(MYO7A):c.93C>A (p.Cys31Ter)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
11860	NM_000260.4(MYO7A):c.1996C>T (p.Arg666Ter)	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
11864	NM_000260.4(MYO7A):c.5143GAG[1] (p.Glu1716del)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1275770	NM_000260.4(MYO7A):c.1740_1747del (p.Val581fs)	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
1334123	NM_000260.4(MYO7A):c.4297C>T (p.Gln1433Ter)	MYO7A	Pathogenic	criteria provided, single submitter
1393609	NM_000260.4(MYO7A):c.3829del (p.Ala1277fs)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1434715	NM_000260.4(MYO7A):c.1829_1832dup (p.Ser611_Ser612insTer)	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
177712	NM_000260.4(MYO7A):c.470+1G>A	MYO7A	Pathogenic	criteria provided, multiple submitters, no conflicts
177722	NM_000260.4(MYO7A):c.73G>A (p.Gly25Arg)	MYO7A	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

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.