Autosomal dominant nonsyndromic hearing loss 17

Summary

Autosomal dominant nonsyndromic hearing loss 17 (MONDO:0011350) is a disease caused by MYH9 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MYH9 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 475

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant nonsyndromic hearing loss 17
Mondo ID	MONDO:0011350
OMIM	603622
DOID	DOID:0110548
UMLS	C1863659
MedGen	350942
GARD	0009726
Is cancer (heuristic)	no

Also known as: autosomal dominant deafness 17 · autosomal dominant nonsyndromic deafness 17 · autosomal dominant nonsyndromic deafness caused by mutation in MYH9 · autosomal dominant nonsyndromic deafness type 17 · deafness, autosomal dominant 17 · deafness, autosomal dominant nonsyndromic sensorineural 17 · deafness, autosomal dominant type 17 · DFNA17 · late-onset progressive hereditary hearing impairment due to cochleosaccular degeneration · MYH9 autosomal dominant nonsyndromic deafness · nonsyndromic hereditary deafness DFNA17

Data availability: 475 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 17

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 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 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

475 retrieved; paginated sample, class counts are floors:

188 uncertain significance, 153 conflicting classifications of pathogenicity, 67 benign/likely benign, 28 benign, 27 likely benign, 5 pathogenic, 5 pathogenic/likely pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14072	NM_002473.6(MYH9):c.5797C>T (p.Arg1933Ter)	MYH9	Pathogenic	criteria provided, multiple submitters, no conflicts
14073	NM_002473.6(MYH9):c.5521G>A (p.Glu1841Lys)	MYH9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14074	NM_002473.6(MYH9):c.3493C>T (p.Arg1165Cys)	MYH9	Pathogenic	criteria provided, multiple submitters, no conflicts
14078	NM_002473.6(MYH9):c.2104C>T (p.Arg702Cys)	MYH9	Pathogenic	criteria provided, multiple submitters, no conflicts
14079	NM_002473.6(MYH9):c.2114G>A (p.Arg705His)	MYH9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14082	NM_002473.6(MYH9):c.4270G>A (p.Asp1424Asn)	MYH9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14083	NM_002473.6(MYH9):c.287C>T (p.Ser96Leu)	MYH9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
164432	NM_002473.6(MYH9):c.4546G>T (p.Val1516Leu)	MYH9	Pathogenic	criteria provided, multiple submitters, no conflicts
3250387	NM_002473.6(MYH9):c.2163T>G (p.Tyr721Ter)	MYH9	Pathogenic	criteria provided, single submitter
623108	NM_002473.6(MYH9):c.2152C>T (p.Arg718Trp)	MYH9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1696214	NM_002473.6(MYH9):c.4546G>A (p.Val1516Met)	MYH9	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3250388	NM_002473.6(MYH9):c.280G>A (p.Glu94Lys)	MYH9	Likely pathogenic	criteria provided, single submitter
164446	NM_002473.6(MYH9):c.2872G>A (p.Ala958Thr)	LOC126863137	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
164448	NM_002473.6(MYH9):c.2714G>A (p.Arg905His)	LOC126863137	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1696936	NM_002473.6(MYH9):c.2713C>T (p.Arg905Cys)	LOC126863137	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3587984	NM_002473.6(MYH9):c.2796G>A (p.Gln932=)	LOC126863137	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3587986	NM_002473.6(MYH9):c.2771T>C (p.Val924Ala)	LOC126863137	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3587987	NM_002473.6(MYH9):c.2692G>A (p.Glu898Lys)	LOC126863137	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
504625	NM_002473.6(MYH9):c.2691C>T (p.Ala897=)	LOC126863137	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
900007	NM_002473.6(MYH9):c.2653C>T (p.Leu885=)	LOC126863137	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1120128	NM_002473.6(MYH9):c.5177G>A (p.Arg1726His)	MYH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1188079	NM_002473.6(MYH9):c.1057G>A (p.Val353Ile)	MYH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1194904	NM_002473.6(MYH9):c.3817G>A (p.Asp1273Asn)	MYH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1200464	NM_002473.6(MYH9):c.4079C>G (p.Ala1360Gly)	MYH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1254859	NM_002473.6(MYH9):c.2618C>T (p.Thr873Met)	MYH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1303195	NM_002473.6(MYH9):c.4352C>T (p.Ala1451Val)	MYH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1304394	NM_002473.6(MYH9):c.4741G>A (p.Glu1581Lys)	MYH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1341864	NM_002473.6(MYH9):c.3193G>A (p.Ala1065Thr)	MYH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1348422	NM_002473.6(MYH9):c.4883C>T (p.Ser1628Leu)	MYH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1361564	NM_002473.6(MYH9):c.3877G>A (p.Asp1293Asn)	MYH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
MYH9	Definitive	Autosomal dominant	macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYH9	Orphanet:182050	MYH9-related syndromic thrombocytopenia
MYH9	Orphanet:477742	Nodular fasciitis
MYH9	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

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
MYH9	HGNC:7579	ENSG00000100345	P35579	Myosin-9	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYH9	Myosin-9	Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.

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)
MYH9	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail

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
ascending aorta	1
stromal cell of endometrium	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYH9	279	ubiquitous	marker	stromal cell of endometrium, ascending aorta, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYH9	5,533

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYH9	P35579	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 40. 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
CD163 mediating an anti-inflammatory response	1	1142.0×	0.009	MYH9
Sema4D in semaphorin signaling	1	671.8×	0.009	MYH9
RHO GTPases activate CIT	1	601.0×	0.009	MYH9
RHO GTPases Activate ROCKs	1	601.0×	0.009	MYH9
Sema4D induced cell migration and growth-cone collapse	1	571.0×	0.009	MYH9
RHO GTPases activate PAKs	1	543.8×	0.009	MYH9
Semaphorin interactions	1	393.8×	0.009	MYH9
Anti-inflammatory response favouring Leishmania parasite infection	1	393.8×	0.009	MYH9
Leishmania parasite growth and survival	1	393.8×	0.009	MYH9
EPHA-mediated growth cone collapse	1	380.7×	0.009	MYH9
Parasite infection	1	346.1×	0.009	MYH9
Leishmania phagocytosis	1	346.1×	0.009	MYH9
RHO GTPases activate PKNs	1	317.2×	0.009	MYH9
Sensory processing of sound	1	308.6×	0.009	MYH9
Fcgamma receptor (FCGR) dependent phagocytosis	1	278.5×	0.009	MYH9
Signaling by ALK in cancer	1	271.9×	0.009	MYH9
Sensory processing of sound by outer hair cells of the cochlea	1	203.9×	0.011	MYH9
FCGR3A-mediated phagocytosis	1	187.2×	0.011	MYH9
Regulation of actin dynamics for phagocytic cup formation	1	184.2×	0.011	MYH9
EPH-Ephrin signaling	1	165.5×	0.011	MYH9
Leishmania infection	1	163.1×	0.011	MYH9
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.011	MYH9
Parasitic Infection Pathways	1	163.1×	0.011	MYH9
Translocation of SLC2A4 (GLUT4) to the plasma membrane	1	154.3×	0.011	MYH9
Signaling by ALK fusions and activated point mutants	1	150.3×	0.011	MYH9
Sensory Perception	1	95.2×	0.016	MYH9
RHO GTPase Effectors	1	68.0×	0.022	MYH9
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.025	MYH9
Axon guidance	1	45.1×	0.031	MYH9
Nervous system development	1	42.9×	0.031	MYH9

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
uropod organization	1	8426.0×	9e-04	MYH9
cortical granule exocytosis	1	8426.0×	9e-04	MYH9
negative regulation of actin filament severing	1	8426.0×	9e-04	MYH9
positive regulation of protein processing in phagocytic vesicle	1	8426.0×	9e-04	MYH9
cytokinetic process	1	5617.3×	9e-04	MYH9
regulation of plasma membrane repair	1	5617.3×	9e-04	MYH9
establishment of meiotic spindle localization	1	4213.0×	0.001	MYH9
cytoplasmic actin-based contraction involved in cell motility	1	3370.4×	0.001	MYH9
meiotic spindle organization	1	2407.4×	0.001	MYH9
establishment of T cell polarity	1	1872.4×	0.002	MYH9
blood vessel endothelial cell migration	1	1404.3×	0.002	MYH9
regulated exocytosis	1	887.0×	0.003	MYH9
actin filament-based movement	1	802.5×	0.003	MYH9
monocyte differentiation	1	802.5×	0.003	MYH9
platelet formation	1	702.2×	0.003	MYH9
phagocytosis, engulfment	1	674.1×	0.003	MYH9
membrane protein ectodomain proteolysis	1	648.1×	0.003	MYH9
leukocyte migration	1	624.1×	0.003	MYH9
myoblast fusion	1	601.9×	0.003	MYH9
plasma membrane repair	1	581.1×	0.003	MYH9
actomyosin structure organization	1	561.7×	0.003	MYH9
lysosome localization	1	526.6×	0.003	MYH9
endodermal cell differentiation	1	495.6×	0.003	MYH9
symbiont entry into host cell	1	401.2×	0.003	MYH9
platelet aggregation	1	337.0×	0.004	MYH9
integrin-mediated signaling pathway	1	160.5×	0.007	MYH9
regulation of cell shape	1	123.0×	0.009	MYH9
actin cytoskeleton organization	1	79.1×	0.014	MYH9
in utero embryonic development	1	72.0×	0.015	MYH9
angiogenesis	1	62.4×	0.017	MYH9

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYH9	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	MYH9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MYH9	10	Binding:10

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	MYH9

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	1	MYH9
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.