autosomal dominant nonsyndromic hearing loss 4A

Summary

autosomal dominant nonsyndromic hearing loss 4A (MONDO:0010915) is a disease caused by MYH14 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MYH14 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 269

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant nonsyndromic hearing loss 4A
Mondo ID	MONDO:0010915
MeSH	C563460
OMIM	600652
DOID	DOID:0110573
UMLS	C1833503
MedGen	322209
GARD	0018100
Is cancer (heuristic)	no

Also known as: autosomal dominant deafness 4A · autosomal dominant nonsyndromic deafness 4A · autosomal dominant nonsyndromic deafness caused by mutation in MYH14 · autosomal dominant nonsyndromic deafness type 4A · deafness, autosomal dominant 4 · deafness, autosomal dominant 4A · deafness, autosomal dominant 4a · deafness, autosomal dominant type 4A · DFNA4A · MYH14 autosomal dominant nonsyndromic deafness

Data availability: 269 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 dominant disease › autosomal dominant nonsyndromic hearing loss › autosomal dominant nonsyndromic hearing loss 4A

Related subtypes (75): autosomal dominant nonsyndromic hearing loss 1, autosomal dominant nonsyndromic hearing loss 2A, 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 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

269 retrieved; paginated sample, class counts are floors:

117 uncertain significance, 69 conflicting classifications of pathogenicity, 44 benign, 20 benign/likely benign, 9 likely benign, 5 pathogenic, 4 likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1185649	NM_001145809.2(MYH14):c.5990del (p.Thr1997fs)	MYH14	Pathogenic	no assertion criteria provided
2196	NM_001145809.2(MYH14):c.20C>A (p.Ser7Ter)	MYH14	Pathogenic	no assertion criteria provided
2198	NM_001145809.2(MYH14):c.2299C>A (p.Arg767Ser)	MYH14	Pathogenic	no assertion criteria provided
3250385	NM_001145809.2(MYH14):c.1368C>G (p.Tyr456Ter)	MYH14	Pathogenic	criteria provided, single submitter
3629635	NM_001145809.2(MYH14):c.3721_3722del (p.Leu1241fs)	MYH14	Pathogenic	criteria provided, single submitter
2505164	NM_001145809.2(MYH14):c.571G>C (p.Asp191His)	MYH14	Likely pathogenic	criteria provided, single submitter
3250384	NM_001145809.2(MYH14):c.587G>T (p.Cys196Phe)	MYH14	Likely pathogenic	criteria provided, single submitter
3250386	NM_001145809.2(MYH14):c.693+1G>A	MYH14	Likely pathogenic	criteria provided, single submitter
3777223	NM_001145809.2(MYH14):c.571G>T (p.Asp191Tyr)	MYH14	Likely pathogenic	criteria provided, single submitter
893859	NM_001145809.2(MYH14):c.909C>T (p.Ala303=)	LOC121852992	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1122300	NM_001145809.2(MYH14):c.1244G>A (p.Gly415Glu)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1217467	NM_001145809.2(MYH14):c.1067C>T (p.Thr356Met)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1310805	NM_001145809.2(MYH14):c.3821G>A (p.Arg1274Gln)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1576001	NM_001145809.2(MYH14):c.4306C>T (p.Arg1436Trp)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
164183	NM_001145809.2(MYH14):c.3514C>A (p.Arg1172=)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
164191	NM_001145809.2(MYH14):c.4259C>T (p.Ala1420Val)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
164195	NM_001145809.2(MYH14):c.4539+10C>T	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178410	NM_001145809.2(MYH14):c.394G>A (p.Gly132Ser)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178411	NM_001145809.2(MYH14):c.565C>T (p.Arg189Cys)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178412	NM_001145809.2(MYH14):c.820A>G (p.Ile274Val)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178414	NM_001145809.2(MYH14):c.1034C>G (p.Ser345Cys)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178419	NM_001145809.2(MYH14):c.3585G>A (p.Ala1195=)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179582	NM_001145809.2(MYH14):c.4152G>A (p.Glu1384=)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2199	NM_001145809.2(MYH14):c.1150G>T (p.Gly384Cys)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2200	NM_001145809.2(MYH14):c.359C>T (p.Ser120Leu)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227572	NM_001145809.2(MYH14):c.1026G>A (p.Pro342=)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
228871	NM_001145809.2(MYH14):c.1919G>A (p.Arg640Gln)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
228876	NM_001145809.2(MYH14):c.3098C>T (p.Thr1033Met)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
228877	NM_001145809.2(MYH14):c.4297G>A (p.Glu1433Lys)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
228878	NM_001145809.2(MYH14):c.526G>A (p.Ala176Thr)	MYH14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 2 · 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
MYH14	Definitive	Autosomal dominant	autosomal dominant nonsyndromic hearing loss 4A	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYH14	Orphanet:397744	MYH14-related peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome
MYH14	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
MYH14	HGNC:23212	ENSG00000105357	Q7Z406	Myosin-14	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYH14	Myosin-14	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)
MYH14	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
gastrocnemius	1
ileal mucosa	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYH14	227	broad	marker	mucosa of transverse colon, ileal mucosa, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYH14	1,569

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYH14	Q7Z406	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Sema4D in semaphorin signaling	1	671.8×	0.006	MYH14
RHO GTPases activate CIT	1	601.0×	0.006	MYH14
RHO GTPases Activate ROCKs	1	601.0×	0.006	MYH14
Sema4D induced cell migration and growth-cone collapse	1	571.0×	0.006	MYH14
RHO GTPases activate PAKs	1	543.8×	0.006	MYH14
Semaphorin interactions	1	393.8×	0.006	MYH14
EPHA-mediated growth cone collapse	1	380.7×	0.006	MYH14
RHO GTPases activate PKNs	1	317.2×	0.006	MYH14
EPH-Ephrin signaling	1	165.5×	0.011	MYH14
RHO GTPase Effectors	1	68.0×	0.024	MYH14
Axon guidance	1	45.1×	0.031	MYH14
Nervous system development	1	42.9×	0.031	MYH14
Signaling by Rho GTPases	1	34.2×	0.034	MYH14
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.034	MYH14
Developmental Biology	1	14.5×	0.074	MYH14
Signal Transduction	1	10.2×	0.098	MYH14

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
vocalization behavior	1	887.0×	0.004	MYH14
actin filament-based movement	1	802.5×	0.004	MYH14
actomyosin structure organization	1	561.7×	0.004	MYH14
skeletal muscle contraction	1	510.7×	0.004	MYH14
neuronal action potential	1	481.5×	0.004	MYH14
skeletal muscle tissue development	1	290.6×	0.006	MYH14
mitotic cytokinesis	1	259.3×	0.006	MYH14
mitochondrion organization	1	151.8×	0.008	MYH14
regulation of cell shape	1	123.0×	0.009	MYH14
sensory perception of sound	1	100.9×	0.010	MYH14

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
MYH14	TUCATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYH14	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TUCATINIB	4	MYH14

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MYH14	1	Binding:1

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)
TUCATINIB	4	MYH14

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MYH14
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	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.