Familial cardiomyopathy

Summary

Familial cardiomyopathy (MONDO:0005217) is a disease (an umbrella term covering 9 Mondo subtypes) with 3 cohort genes.

At a glance

• Umbrella term: 9 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 39

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial cardiomyopathy
Mondo ID	MONDO:0005217
EFO	EFO:0002945
ICD-11	1018022925
SNOMED CT	35728003
UMLS	C0264789
MedGen	538845
GARD	0024166
Is cancer (heuristic)	no

Also known as: hereditary cardiomyopathy

Data availability: 39 ClinVar variants.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › familial cardiomyopathy

Related subtypes (11): Keshan disease, intrinsic cardiomyopathy, extrinsic cardiomyopathy, idiopathic cardiomyopathy, non-compaction cardiomyopathy, Chagas cardiomyopathy, Uhl anomaly, Tako-tsubo cardiomyopathy, cardiomyopathy due to anthracyclines, doxorubicin induced cardiomyopathy, autoimmune cardiomyopathy

Subtypes (9): Naxos disease, fatal infantile encephalocardiomyopathy, familial dilated cardiomyopathy, familial restrictive cardiomyopathy, familial isolated arrhythmogenic right ventricular dysplasia, left ventricular noncompaction, familial hypertrophic cardiomyopathy, NKX2.5-related congenital, conduction and myopathic heart disease, PRKAG2-related 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

39 retrieved; paginated sample, class counts are floors:

15 uncertain significance, 8 pathogenic, 6 likely pathogenic, 5 likely benign, 3 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
132911	NM_000257.4(MYH7):c.2366del (p.Gln789fs)	LOC126861898	Pathogenic	no assertion criteria provided
132914	NM_000257.4(MYH7):c.2163-1G>A	MYH7	Pathogenic	criteria provided, single submitter
132916	NM_000257.4(MYH7):c.2051T>G (p.Met684Arg)	MYH7	Pathogenic	no assertion criteria provided
132917	NM_000257.4(MYH7):c.2028del (p.Asn676fs)	MYH7	Pathogenic	no assertion criteria provided
132920	NM_000257.4(MYH7):c.1956+2T>G	MYH7	Pathogenic	no assertion criteria provided
132925	NM_000257.4(MYH7):c.1573G>A (p.Glu525Lys)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
132926	NM_000257.4(MYH7):c.1530C>A (p.Phe510Leu)	MYH7	Pathogenic	no assertion criteria provided
132930	NM_000257.4(MYH7):c.1151C>A (p.Ser384Tyr)	MYH7	Pathogenic	no assertion criteria provided
132933	NM_000257.4(MYH7):c.1073A>T (p.His358Leu)	MYH7	Pathogenic	no assertion criteria provided
43420	NM_001018005.2(TPM1):c.475G>A (p.Asp159Asn)	TPM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42912	NM_000257.4(MYH7):c.2525G>A (p.Ser842Asn)	LOC126861898	Likely pathogenic	criteria provided, multiple submitters, no conflicts
132908	NM_000257.4(MYH7):c.2686G>A (p.Asp896Asn)	MYH7	Likely pathogenic	criteria provided, single submitter
132913	NM_000257.4(MYH7):c.2174T>C (p.Leu725Pro)	MYH7	Likely pathogenic	no assertion criteria provided
132928	NM_000257.4(MYH7):c.1267G>A (p.Ala423Thr)	MYH7	Likely pathogenic	no assertion criteria provided
132931	NM_000257.4(MYH7):c.1101G>T (p.Lys367Asn)	MYH7	Likely pathogenic	no assertion criteria provided
132934	NM_000257.4(MYH7):c.640-1G>A	MYH7	Likely pathogenic	no assertion criteria provided
132937	NM_000257.4(MYH7):c.503-4A>G	MYH7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
42886	NM_000257.4(MYH7):c.2168G>A (p.Arg723His)	MYH7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201953	NM_014476.6(PDLIM3):c.715G>A (p.Asp239Asn)	PDLIM3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
132910	NM_000257.4(MYH7):c.2469G>T (p.Gly823=)	LOC126861898	Uncertain significance	no assertion criteria provided
132907	NM_000257.4(MYH7):c.3245+149C>G	MYH7	Uncertain significance	no assertion criteria provided
132912	NM_000257.4(MYH7):c.2181A>G (p.Pro727=)	MYH7	Uncertain significance	no assertion criteria provided
132918	NM_000257.4(MYH7):c.1956+114G>A	MYH7	Uncertain significance	no assertion criteria provided
132919	NM_000257.4(MYH7):c.1956+112G>A	MYH7	Uncertain significance	no assertion criteria provided
132921	NM_000257.4(MYH7):c.1952A>G (p.His651Arg)	MYH7	Uncertain significance	criteria provided, single submitter
132922	NM_000257.4(MYH7):c.1889-27T>A	MYH7	Uncertain significance	no assertion criteria provided
132923	NM_000257.4(MYH7):c.1830G>A (p.Gln610=)	MYH7	Uncertain significance	no assertion criteria provided
132927	NM_000257.4(MYH7):c.1291G>A (p.Val431Met)	MYH7	Uncertain significance	criteria provided, multiple submitters, no conflicts
132935	NM_000257.4(MYH7):c.639+31C>A	MYH7	Uncertain significance	no assertion criteria provided
132936	NM_000257.4(MYH7):c.639+28T>A	MYH7	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TPM1	Orphanet:154	Familial isolated dilated cardiomyopathy
TPM1	Orphanet:54260	Left ventricular noncompaction
MYH7	Orphanet:154	Familial isolated dilated cardiomyopathy
MYH7	Orphanet:1880	Ebstein malformation of the tricuspid valve
MYH7	Orphanet:324604	Classic multiminicore myopathy
MYH7	Orphanet:54260	Left ventricular noncompaction
MYH7	Orphanet:59135	Laing distal myopathy
MYH7	Orphanet:636965	Autosomal dominant myosin storage myopathy
MYH7	Orphanet:636970	Autosomal recessive myosin storage myopathy

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TPM1	HGNC:12010	ENSG00000140416	P09493	Tropomyosin alpha-1 chain	clinvar
PDLIM3	HGNC:20767	ENSG00000154553	Q53GG5	PDZ and LIM domain protein 3	clinvar
MYH7	HGNC:7577	ENSG00000092054	P12883	Myosin-7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TPM1	Tropomyosin alpha-1 chain	Binds to actin filaments in muscle and non-muscle cells.
PDLIM3	PDZ and LIM domain protein 3	May play a role in the organization of actin filament arrays within muscle cells.
MYH7	Myosin-7	Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 1 · 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	5.8×	0.482
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TPM1	Other/Unknown	no		Tropomyosin
PDLIM3	Transcription factor	no		PDZ, Znf_LIM, Zasp-like_motif
MYH7	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	2
skeletal muscle tissue of biceps brachii	2
heart right ventricle	1
left ventricle myocardium	1
myocardium	1
gluteal muscle	1
apex of heart	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TPM1	305	ubiquitous	marker	left ventricle myocardium, heart right ventricle, myocardium
PDLIM3	264	ubiquitous	marker	gluteal muscle, hindlimb stylopod muscle, skeletal muscle tissue of biceps brachii
MYH7	167	tissue_specific	marker	apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TPM1	3,514
MYH7	2,744
PDLIM3	1,568

Intra-cohort edges

A	B	Sources
MYH7	TPM1	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYH7	P12883	43
TPM1	P09493	14

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PDLIM3	Q53GG5	66.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 3 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×	0.004	TPM1
Smooth Muscle Contraction	1	265.6×	0.004	TPM1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
muscle filament sliding	2	702.2×	8e-05	TPM1, MYH7
ventricular cardiac muscle tissue morphogenesis	2	468.1×	9e-05	TPM1, MYH7
cardiac muscle contraction	2	267.5×	2e-04	TPM1, MYH7
positive regulation of heart rate by epinephrine	1	5617.3×	0.001	TPM1
actin filament organization	2	79.1×	0.001	TPM1, PDLIM3
regulation of slow-twitch skeletal muscle fiber contraction	1	2808.7×	0.002	MYH7
regulation of the force of skeletal muscle contraction	1	1872.4×	0.002	MYH7
transition between fast and slow fiber	1	802.5×	0.005	MYH7
regulation of muscle contraction	1	561.7×	0.006	TPM1
negative regulation of vascular associated smooth muscle cell migration	1	561.7×	0.006	TPM1
muscle structure development	1	468.1×	0.006	PDLIM3
ruffle organization	1	432.1×	0.006	TPM1
adult heart development	1	401.2×	0.006	MYH7
cardiac muscle hypertrophy in response to stress	1	351.1×	0.006	MYH7
regulation of the force of heart contraction	1	330.4×	0.006	MYH7
striated muscle contraction	1	280.9×	0.007	MYH7
negative regulation of vascular associated smooth muscle cell proliferation	1	224.7×	0.008	TPM1
skeletal muscle contraction	1	170.2×	0.010	MYH7
regulation of heart contraction	1	165.2×	0.010	TPM1
regulation of heart rate	1	156.0×	0.010	MYH7
ATP metabolic process	1	156.0×	0.010	MYH7
cellular response to reactive oxygen species	1	137.0×	0.011	TPM1
sarcomere organization	1	127.7×	0.011	TPM1
positive regulation of stress fiber assembly	1	104.0×	0.013	TPM1
positive regulation of cell adhesion	1	90.6×	0.014	TPM1
wound healing	1	75.9×	0.016	TPM1
muscle contraction	1	69.3×	0.017	MYH7
cytoskeleton organization	1	44.2×	0.026	TPM1
regulation of cell shape	1	41.0×	0.027	TPM1
negative regulation of cell migration	1	37.2×	0.028	TPM1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TPM1	0	0
PDLIM3	0	0
MYH7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TPM1	3	Binding:3

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	TPM1, PDLIM3, MYH7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TPM1	3	—
PDLIM3	0	—
MYH7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.