cardiomyopathy, dilated, 2I

Summary

cardiomyopathy, dilated, 2I (MONDO:0957545) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cardiomyopathy, dilated, 2I
Mondo ID	MONDO:0957545
OMIM	620462
UMLS	C5830685
MedGen	1841321
GARD	0026864
Is cancer (heuristic)	no

Data availability: 7 ClinVar variants · 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 › dilated cardiomyopathy › familial dilated cardiomyopathy › cardiomyopathy, dilated, 2I

Related subtypes (28): autosomal recessive limb-girdle muscular dystrophy type 2C, Barth syndrome, histiocytoid cardiomyopathy, Kearns-Sayre syndrome, Leber hereditary optic neuropathy, autosomal recessive limb-girdle muscular dystrophy type 2F, myofibrillar myopathy 1, autosomal recessive limb-girdle muscular dystrophy type 2E, dilated cardiomyopathy 1J, hypertrophic cardiomyopathy 25, autosomal recessive limb-girdle muscular dystrophy type 2D, DK1-congenital disorder of glycosylation, autosomal recessive limb-girdle muscular dystrophy type 2M, early-onset myopathy with fatal cardiomyopathy, PGM1-congenital disorder of glycosylation, autosomal recessive limb-girdle muscular dystrophy type 2W, symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers, Emery-Dreifuss muscular dystrophy, familial isolated dilated cardiomyopathy, cardiomyopathy, dilated, 1LL, cardiomyopathy, dilated, 1MM, cardiomyopathy, dilated, 100, cardiomyopathy, dilated, 2j, cardiomyopathy, dilated, 2K, cardiomyopathy, dilated, 2l, cardiomyopathy, dilated, 1QQ, cardiomyopathy, dilated, 2M, cardiomyopathy, dilated, 3C

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

7 retrieved; paginated sample, class counts are floors:

3 pathogenic, 3 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2574649	NM_006366.3(CAP2):c.636+1G>A	CAP2	Pathogenic	no assertion criteria provided
2574650	NM_006366.3(CAP2):c.948T>G (p.Tyr316Ter)	CAP2	Pathogenic	no assertion criteria provided
2574651	NM_006366.3(CAP2):c.1288del (p.Cys430fs)	CAP2	Pathogenic	no assertion criteria provided
4845338	NM_006366.3(CAP2):c.870del (p.Ser291fs)	CAP2	Likely pathogenic	criteria provided, single submitter
2688715	NM_006366.3(CAP2):c.2T>C (p.Met1Thr)	CAP2	Uncertain significance	criteria provided, single submitter
3064269	NM_006366.3(CAP2):c.38G>A (p.Arg13Gln)	CAP2	Uncertain significance	criteria provided, single submitter
3137007	NM_006366.3(CAP2):c.50G>A (p.Arg17His)	CAP2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
CAP2	Moderate	Autosomal recessive	cardiomyopathy, dilated, 2I	2
TMPRSS4	Moderate	Autosomal recessive	cardiomyopathy, dilated, 2I	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TMPRSS4	Orphanet:363969	Autosomal recessive cerebral atrophy
CAP2	Orphanet:154	Familial isolated dilated cardiomyopathy

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TMPRSS4	HGNC:11878	ENSG00000137648	Q9NRS4	Transmembrane protease serine 4	gencc,clinvar
CAP2	HGNC:20039	ENSG00000112186	P40123	Adenylyl cyclase-associated protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TMPRSS4	Transmembrane protease serine 4	Plasma membrane-anchored serine protease that directly induces processing of pro-uPA/PLAU into the active form through proteolytic activity.
CAP2	Adenylyl cyclase-associated protein 2	Involved in the regulation of actin polymerization.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Protease	1	18.3×	0.108
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TMPRSS4	Protease	yes		SRCR, Trypsin_dom, Peptidase_S1A
CAP2	Other/Unknown	no		Adenylate_cyclase-assoc_CAP, CARP_motif, Adenylate_cyclase-assoc_CAP_C

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus mucosa	1
mucosa of transverse colon	1
nasal cavity epithelium	1
Brodmann (1909) area 23	1
biceps brachii	1
skeletal muscle tissue of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TMPRSS4	195	broad	marker	mucosa of transverse colon, lower esophagus mucosa, nasal cavity epithelium
CAP2	280	ubiquitous	marker	skeletal muscle tissue of biceps brachii, biceps brachii, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TMPRSS4	1,671
CAP2	1,170

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TMPRSS4	Q9NRS4	88.01
CAP2	P40123	83.78

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 2 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
Role of ABL in ROBO-SLIT signaling	1	1268.9×	0.004	CAP2
Signaling by ROBO receptors	1	124.1×	0.020	CAP2
Axon guidance	1	45.1×	0.029	CAP2
Nervous system development	1	42.9×	0.029	CAP2
Developmental Biology	1	14.5×	0.069	CAP2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete cAMP-mediated signaling	1	2808.7×	0.002	CAP2
negative regulation of growth rate	1	2808.7×	0.002	TMPRSS4
presynaptic actin cytoskeleton organization	1	1685.2×	0.003	CAP2
positive regulation of viral entry into host cell	1	601.9×	0.005	TMPRSS4
activation of adenylate cyclase activity	1	561.7×	0.005	CAP2
establishment or maintenance of cell polarity	1	200.6×	0.011	CAP2
response to wounding	1	110.9×	0.017	TMPRSS4
protein processing	1	85.1×	0.018	TMPRSS4
cell morphogenesis	1	78.8×	0.018	CAP2
actin filament organization	1	59.3×	0.022	CAP2
regulation of gene expression	1	41.7×	0.028	TMPRSS4
proteolysis	1	17.1×	0.062	TMPRSS4
signal transduction	1	8.0×	0.121	CAP2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TMPRSS4	1	1
CAP2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IMD-0354	1	TMPRSS4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TMPRSS4	21	Binding:21

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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)
IMD-0354	1	TMPRSS4

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	TMPRSS4
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CAP2

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)
CAP2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.