Progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome

Summary

Progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome (MONDO:0016424) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome
Mondo ID	MONDO:0016424
Orphanet	228012
UMLS	C4304831
MedGen	930500
GARD	0017145
Is cancer (heuristic)	no

Also known as: progressive neurosensory deafness-hypertrophic cardiomyopathy syndrome · progressive neurosensory hearing loss-hypertrophic cardiomyopathy syndrome · progressive sensorineural deafness-hypertrophic cardiomyopathy syndrome

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › hypertrophic cardiomyopathy › progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome

Related subtypes (2): non-familial hypertrophic cardiomyopathy, familial hypertrophic cardiomyopathy

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
8581	NM_004999.4(MYO6):c.737A>G (p.His246Arg)	MYO6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

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.