MYH-6 related congenital heart defects

Summary

MYH-6 related congenital heart defects (MONDO:0800442) is a disease caused by MYH6 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MYH6 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	MYH-6 related congenital heart defects
Mondo ID	MONDO:0800442
Is cancer (heuristic)	no

Also known as: MYH6 related congenital heart defects

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › congenital heart defects, multiple types › MYH-6 related congenital heart defects

Related subtypes (7): congenital heart defects, multiple types, 6, congenital heart defects, multiple types, 3, congenital heart defects, multiple types, 2, congenital heart defects, multiple types, 4, congenital heart defects, multiple types, 5, congenital heart defects, multiple types, 8, with or without heterotaxy, congenital heart defects, multiple types, 9

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

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3906859	NM_002471.4(MYH6):c.953A>G (p.Glu318Gly)	MYH6	Uncertain significance	no assertion criteria provided
4531476	NM_002471.4(MYH6):c.2963A>G (p.Asp988Gly)	MYH6	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
MYH6	Definitive	Autosomal dominant	MYH-6 related congenital heart defects	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYH6	Orphanet:154	Familial isolated dilated cardiomyopathy
MYH6	Orphanet:166282	Hereditary sick sinus syndrome
MYH6	Orphanet:99103	Atrial septal defect, ostium secundum type

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
MYH6	HGNC:7576	ENSG00000197616	P13533	Myosin-6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYH6	Myosin-6	Muscle contraction.

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)
MYH6	Scaffold/PPI	no		Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin

Expression context

Cohort genes with no expression data: 0.

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
cardiac atrium	1
cardiac muscle of right atrium	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYH6	154	tissue_specific	yes	cardiac muscle of right atrium, cardiac atrium, vena cava

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYH6	3,119

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYH6	P13533	74.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Striated Muscle Contraction	1	308.6×	0.006	MYH6
Muscle contraction	1	77.2×	0.013	MYH6

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
visceral muscle development	1	16852.0×	0.001	MYH6
regulation of heart growth	1	8426.0×	0.001	MYH6
atrial cardiac muscle tissue morphogenesis	1	2407.4×	0.002	MYH6
adult heart development	1	1203.7×	0.002	MYH6
myofibril assembly	1	1123.5×	0.002	MYH6
cardiac muscle hypertrophy in response to stress	1	1053.2×	0.002	MYH6
muscle filament sliding	1	1053.2×	0.002	MYH6
regulation of the force of heart contraction	1	991.3×	0.002	MYH6
striated muscle contraction	1	842.6×	0.003	MYH6
ventricular cardiac muscle tissue morphogenesis	1	702.2×	0.003	MYH6
cardiac muscle cell development	1	624.1×	0.003	MYH6
regulation of heart contraction	1	495.6×	0.003	MYH6
regulation of heart rate	1	468.1×	0.003	MYH6
ATP metabolic process	1	468.1×	0.003	MYH6
cardiac muscle contraction	1	401.2×	0.003	MYH6
sarcomere organization	1	383.0×	0.003	MYH6
regulation of blood pressure	1	221.7×	0.005	MYH6
muscle contraction	1	208.1×	0.005	MYH6
in utero embryonic development	1	72.0×	0.014	MYH6

Therapeutics

Drug target analysis

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

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
MYH6	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	MYH6

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)
MYH6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.