dilated cardiomyopathy 3B

Summary

dilated cardiomyopathy 3B (MONDO:0010542) is a disease caused by DMD (GenCC Definitive), with 4 cohort genes and 1 clinical trial. The dominant Reactome pathway is Formation of the dystrophin-glycoprotein complex (DGC) (3 cohort genes).

At a glance

• Causal gene: DMD (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 431
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 3B
Mondo ID	MONDO:0010542
MeSH	C580047
OMIM	302045
DOID	DOID:0060561, DOID:0081164, DOID:0110461
SNOMED CT	702424003
UMLS	C3668940
MedGen	777148
GARD	0015287
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 3B · cardiomyopathy, dilated, type 3B · CMD3B · dilated cardiomyopathy 3B · dilated cardiomyopathy caused by mutation in DMD · dilated cardiomyopathy type 3B · DMD dilated cardiomyopathy

Data availability: 431 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › qualitative or quantitative protein defects in neuromuscular diseases › neuromuscular disease caused by qualitative or quantitative defects of dystrophin › dilated cardiomyopathy 3B

Related subtypes (1): isolated asymptomatic elevation of creatine phosphokinase

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

431 retrieved; paginated sample, class counts are floors:

152 conflicting classifications of pathogenicity, 126 uncertain significance, 44 pathogenic, 43 benign/likely benign, 33 benign, 16 likely benign, 11 likely pathogenic, 6 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072276	NM_004006.3(DMD):c.1603-2A>T	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
11213	NM_004006.3(DMD):c.10108C>T (p.Arg3370Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
11225	NM_004006.3(DMD):c.433C>T (p.Arg145Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
11231	NC_000023.11:g.(33020201_33211281)(33211556?)del	DMD	Pathogenic	no assertion criteria provided
11281	NG_012232.1:g.702849_702850insinsY13186.2:g.2333_2491	DMD	Pathogenic	no assertion criteria provided
11282	NM_004006.3(DMD):c.9568C>T (p.Arg3190Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
11288	NM_004006.3(DMD):c.8713C>T (p.Arg2905Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
1180800	NM_004006.3(DMD):c.6576G>A (p.Trp2192Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
1285470	NM_004006.3(DMD):c.4684del (p.Arg1562fs)	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322265	NM_004006.3(DMD):c.3556G>T (p.Glu1186Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
1322340	NM_004006.3(DMD):c.1375G>T (p.Glu459Ter)	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455387	NM_004006.3(DMD):c.10453_10454del (p.Leu3485fs)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
193663	NM_004006.3(DMD):c.1093C>T (p.Gln365Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
1966748	NM_004006.3(DMD):c.6613_6614del (p.Arg2205fs)	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217199	NM_004006.3(DMD):c.4729C>T (p.Arg1577Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
2500346	NM_004006.3:c.(6438+1_6439-1)_(6614+1_6615-1)del	DMD	Pathogenic	criteria provided, single submitter
2737168	NM_004006.3(DMD):c.2623-2A>G	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
284288	NM_004006.3(DMD):c.10098AGA[1] (p.Glu3367del)	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
284924	NM_004006.3(DMD):c.457C>T (p.Gln153Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
288923	NM_004006.3(DMD):c.4483C>T (p.Gln1495Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
29962	NM_004006.3(DMD):c.9G>A (p.Trp3Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
3381849	NM_004006.3(DMD):c.5637G>A (p.Trp1879Ter)	DMD	Pathogenic	criteria provided, single submitter
3381933	NM_004006.3(DMD):c.875del (p.Pro292fs)	DMD	Pathogenic	criteria provided, single submitter
3382430	NM_004006.3(DMD):c.985_991del (p.Ser329fs)	DMD	Pathogenic	criteria provided, single submitter
3382794	NM_004006.3(DMD):c.10484T>A (p.Leu3495Ter)	DMD	Pathogenic	criteria provided, single submitter
3382928	NM_004006.3(DMD):c.4474_4475del (p.Ser1492fs)	DMD	Pathogenic	criteria provided, single submitter
3383042	NM_004006.3(DMD):c.3305_3308dup (p.Ser1104fs)	DMD	Pathogenic	criteria provided, single submitter
3598266	NM_004006.3(DMD):c.10509del (p.Glu3505fs)	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3598267	NM_004006.3(DMD):c.8111G>A (p.Trp2704Ter)	DMD	Pathogenic	criteria provided, single submitter
374191	NM_004006.3(DMD):c.1637G>A (p.Trp546Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 12 · 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
DMD	Definitive	X-linked	dilated cardiomyopathy 3B	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DMD	Orphanet:154	Familial isolated dilated cardiomyopathy
DMD	Orphanet:206546	Symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers
DMD	Orphanet:777	X-linked non-syndromic intellectual disability
DMD	Orphanet:98895	Becker muscular dystrophy
DMD	Orphanet:98896	Duchenne muscular dystrophy
SNTA1	Orphanet:101016	Romano-Ward syndrome
LAMA4	Orphanet:154	Familial isolated dilated cardiomyopathy
PKP2	Orphanet:130	Brugada syndrome
PKP2	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
PKP2	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
PKP2	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
PKP2	Orphanet:54260	Left ventricular noncompaction

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DMD	HGNC:2928	ENSG00000198947	P11532	Dystrophin	gencc,clinvar
SNTA1	HGNC:11167	ENSG00000101400	Q13424	Alpha-1-syntrophin	clinvar
LAMA4	HGNC:6484	ENSG00000112769	Q16363	Laminin subunit alpha-4	clinvar
PKP2	HGNC:9024	ENSG00000057294	Q99959	Plakophilin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DMD	Dystrophin	Anchors the extracellular matrix to the cytoskeleton via F-actin.
SNTA1	Alpha-1-syntrophin	Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins.
LAMA4	Laminin subunit alpha-4	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
PKP2	Plakophilin-2	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 2 · 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	4.3×	0.605
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DMD	Transcription factor	no		Znf_ZZ, WW_dom, Actinin_actin-bd_CS
SNTA1	Scaffold/PPI	no		PDZ, PH_domain, PH-like_dom_sf
LAMA4	Other/Unknown	no		EGF, Laminin_G, LE_dom
PKP2	Other/Unknown	no		Armadillo, ARM-like, ARM-type_fold

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	2
dorsal root ganglion	1
skeletal muscle tissue of rectus abdominis	1
trigeminal ganglion	1
gastrocnemius	1
hindlimb stylopod muscle	1
lower esophagus	1
lower esophagus muscularis layer	1
nerve	1
heart right ventricle	1
left ventricle myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DMD	295	ubiquitous	marker	trigeminal ganglion, skeletal muscle tissue of rectus abdominis, dorsal root ganglion
SNTA1	266	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius
LAMA4	268	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, nerve
PKP2	237	ubiquitous	marker	heart right ventricle, apex of heart, left ventricle myocardium

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LAMA4	2,688
DMD	2,479
PKP2	1,861
SNTA1	1,499

Intra-cohort edges

A	B	Sources
DMD	SNTA1	biogrid_interaction, intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DMD	P11532	6
PKP2	Q99959	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SNTA1	Q13424	80.00
LAMA4	Q16363	73.75

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the dystrophin-glycoprotein complex (DGC)	3	231.5×	2e-06	DMD, SNTA1, LAMA4
Non-integrin membrane-ECM interactions	3	115.7×	8e-06	DMD, SNTA1, LAMA4
Extracellular matrix organization	2	31.6×	0.007	SNTA1, LAMA4
MET promotes cell motility	1	150.3×	0.021	LAMA4
Attachment of bacteria to epithelial cells	1	124.1×	0.021	LAMA4
Laminin interactions	1	95.2×	0.021	LAMA4
MET activates PTK2 signaling	1	95.2×	0.021	LAMA4
Signaling by MET	1	79.3×	0.021	LAMA4
Striated Muscle Contraction	1	77.2×	0.021	DMD
Developmental Lineage of Pancreatic Ductal Cells	1	57.1×	0.026	LAMA4
ECM proteoglycans	1	37.6×	0.036	LAMA4
Formation of the cornified envelope	1	22.0×	0.056	PKP2
Keratinization	1	13.9×	0.081	PKP2
Signaling by Receptor Tyrosine Kinases	1	12.9×	0.081	LAMA4
Signal Transduction	1	2.5×	0.339	LAMA4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 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 sodium ion transmembrane transport	2	526.6×	1e-04	DMD, SNTA1
ventricular cardiac muscle cell action potential	2	495.6×	1e-04	SNTA1, PKP2
regulation of heart rate	2	234.1×	5e-04	DMD, SNTA1
regulation of muscle system process	1	4213.0×	0.002	DMD
regulation of cellular response to growth factor stimulus	1	4213.0×	0.002	DMD
maintenance of protein localization at cell tip	1	4213.0×	0.002	PKP2
cardiac muscle cell action potential	1	2106.5×	0.004	DMD
regulation of cell-substrate adhesion	1	1404.3×	0.005	PKP2
regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion	1	1053.2×	0.005	DMD
peptide biosynthetic process	1	1053.2×	0.005	DMD
maintenance of animal organ identity	1	842.6×	0.005	PKP2
regulation of substrate adhesion-dependent cell spreading	1	842.6×	0.005	PKP2
regulation of skeletal muscle contraction	1	702.2×	0.005	DMD
intermediate filament bundle assembly	1	702.2×	0.005	PKP2
desmosome assembly	1	601.9×	0.005	PKP2
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	1	601.9×	0.005	PKP2
desmosome organization	1	526.6×	0.005	PKP2
regulation of calcium ion transmembrane transport	1	526.6×	0.005	DMD
synaptic signaling	1	383.0×	0.007	DMD
cell communication by electrical coupling involved in cardiac conduction	1	351.1×	0.007	PKP2
regulation of ventricular cardiac muscle cell action potential	1	351.1×	0.007	PKP2
muscle cell development	1	234.1×	0.010	DMD
positive regulation of sodium ion transport	1	210.7×	0.010	PKP2
regulation of ventricular cardiac muscle cell membrane repolarization	1	210.7×	0.010	SNTA1
response to muscle stretch	1	191.5×	0.010	DMD
ventricular cardiac muscle tissue morphogenesis	1	175.5×	0.010	PKP2
cardiac muscle cell action potential involved in contraction	1	175.5×	0.010	PKP2
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	168.5×	0.010	DMD
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	1	168.5×	0.010	DMD
positive regulation of Rac protein signal transduction	1	162.0×	0.010	SNTA1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 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
DMD	0	0
SNTA1	0	0
LAMA4	0	0
PKP2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	4	DMD, SNTA1, LAMA4, PKP2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DMD	0	—
SNTA1	0	—
LAMA4	0	—
PKP2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04139460	Not specified	UNKNOWN	CRT-P or CRT-D in Dilated Cardiomyopathy