dilated cardiomyopathy 1JJ

Summary

dilated cardiomyopathy 1JJ (MONDO:0014095) is a disease caused by LAMA4 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: LAMA4 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 1,441

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1JJ
Mondo ID	MONDO:0014095
OMIM	615235
DOID	DOID:0110438
UMLS	C3808935
MedGen	815265
GARD	0015924
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 1JJ · cardiomyopathy, dilated, type 1Jj · CMD1JJ · dilated cardiomyopathy type 1JJ · familial isolated dilated cardiomyopathy caused by mutation in LAMA4 · LAMA4 familial isolated dilated cardiomyopathy

Data availability: 1,441 ClinVar variants · 4 GenCC gene-disease records.

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 › familial isolated dilated cardiomyopathy › dilated cardiomyopathy 1JJ

Related subtypes (44): dilated cardiomyopathy 1A, dilated cardiomyopathy 3B, dilated cardiomyopathy 1B, dilated cardiomyopathy 1E, dilated cardiomyopathy 1C, dilated cardiomyopathy 1D, dilated cardiomyopathy 1G, dilated cardiomyopathy 1H, dilated cardiomyopathy 1I, dilated cardiomyopathy 1K, dilated cardiomyopathy 1L, dilated cardiomyopathy 1M, dilated cardiomyopathy 1O, dilated cardiomyopathy 1P, dilated cardiomyopathy 1Q, dilated cardiomyopathy 1W, dilated cardiomyopathy 1X, dilated cardiomyopathy 1Y, dilated cardiomyopathy 1Z, dilated cardiomyopathy 2A, dilated cardiomyopathy 1AA, dilated cardiomyopathy 1BB, dilated cardiomyopathy 1CC, dilated cardiomyopathy 1DD, dilated cardiomyopathy 1EE, dilated cardiomyopathy 1FF, dilated cardiomyopathy 1R, dilated cardiomyopathy 1S, dilated cardiomyopathy 1GG, dilated cardiomyopathy 1U, dilated cardiomyopathy 1V, dilated cardiomyopathy 1HH, dilated cardiomyopathy 2B, dilated cardiomyopathy 1II, dilated cardiomyopathy 1KK, left ventricular noncompaction 8, left ventricular noncompaction 10, dilated cardiomyopathy 1NN, cardiomyopathy, dilated, 2D, cardiomyopathy, dilated, 2E, cardiomyopathy, dilated, 2F, cardiomyopathy, dilated, 2G, cardiomyopathy, dilated, 2c, cardiomyopathy, dilated, 2H

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

600 retrieved; paginated sample, class counts are floors:

352 uncertain significance, 177 likely benign, 40 conflicting classifications of pathogenicity, 22 benign/likely benign, 9 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1014034	NM_001105206.3(LAMA4):c.5288T>C (p.Ile1763Thr)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1035819	NM_001105206.3(LAMA4):c.4135G>A (p.Val1379Met)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1059841	NM_001105206.3(LAMA4):c.1744C>G (p.Leu582Val)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1093580	NM_001105206.3(LAMA4):c.3060C>T (p.Asn1020=)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1116759	NM_001105206.3(LAMA4):c.298-5C>G	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1311224	NM_001105206.3(LAMA4):c.1411T>C (p.Phe471Leu)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1311664	NM_001105206.3(LAMA4):c.2096G>A (p.Gly699Asp)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1376965	NM_001105206.3(LAMA4):c.967-16A>G	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1436240	NM_001105206.3(LAMA4):c.4346G>A (p.Arg1449Gln)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1444889	NM_001105206.3(LAMA4):c.2665A>C (p.Asn889His)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1445096	NM_001105206.3(LAMA4):c.4967G>T (p.Gly1656Val)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1515602	NM_001105206.3(LAMA4):c.3964A>G (p.Thr1322Ala)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1524399	NM_001105206.3(LAMA4):c.3256G>A (p.Gly1086Ser)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1596134	NM_001105206.3(LAMA4):c.1960-5T>C	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
163796	NM_001105206.3(LAMA4):c.412C>T (p.His138Tyr)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1678238	NM_001105206.3(LAMA4):c.1077+11A>G	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1768163	NM_001105206.3(LAMA4):c.998C>T (p.Ala333Val)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
177973	NM_001105206.3(LAMA4):c.1959T>C (p.Asp653=)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178049	NM_001105206.3(LAMA4):c.5344C>T (p.Arg1782Cys)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178053	NM_001105206.3(LAMA4):c.2569G>A (p.Ala857Thr)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1781347	NM_001105206.3(LAMA4):c.1873A>G (p.Asn625Asp)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1784720	NM_001105206.3(LAMA4):c.202A>G (p.Asn68Asp)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1789258	NM_001105206.3(LAMA4):c.22C>T (p.Arg8Cys)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178995	NM_001105206.3(LAMA4):c.4405G>A (p.Ala1469Thr)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179673	NM_001105206.3(LAMA4):c.4476-4C>A	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1797705	NM_001105206.3(LAMA4):c.1141G>A (p.Ala381Thr)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
180389	NM_001105206.3(LAMA4):c.631A>C (p.Asn211His)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
180391	NM_001105206.3(LAMA4):c.2614C>G (p.Pro872Ala)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
192119	NM_001105206.3(LAMA4):c.2398C>T (p.Arg800Cys)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
192120	NM_001105206.3(LAMA4):c.1277T>C (p.Met426Thr)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 1 · 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
LAMA4	Strong	Autosomal dominant	dilated cardiomyopathy 1JJ	18

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LAMA4	Orphanet:154	Familial isolated dilated cardiomyopathy

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LAMA4	HGNC:6484	ENSG00000112769	Q16363	Laminin subunit alpha-4	gencc,clinvar
LAMA4-AS1	HGNC:40333	ENSG00000226440		LAMA4 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LAMA4	Other/Unknown	no		EGF, Laminin_G, LE_dom
LAMA4-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus	2
lower esophagus muscularis layer	2
nerve	1
esophagogastric junction muscularis propria	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LAMA4	268	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, nerve
LAMA4-AS1	153		yes	lower esophagus muscularis layer, lower esophagus, esophagogastric junction muscularis propria

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LAMA4	2,688
LAMA4-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LAMA4	Q16363	73.75

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
MET promotes cell motility	1	601.0×	0.006	LAMA4
Attachment of bacteria to epithelial cells	1	496.5×	0.006	LAMA4
Laminin interactions	1	380.7×	0.006	LAMA4
MET activates PTK2 signaling	1	380.7×	0.006	LAMA4
Signaling by MET	1	317.2×	0.006	LAMA4
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.006	LAMA4
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.008	LAMA4
Non-integrin membrane-ECM interactions	1	154.3×	0.009	LAMA4
ECM proteoglycans	1	150.3×	0.009	LAMA4
Extracellular matrix organization	1	63.1×	0.019	LAMA4
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.021	LAMA4
Signal Transduction	1	10.2×	0.098	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of cold-induced thermogenesis	1	343.9×	0.005	LAMA4
regulation of embryonic development	1	330.4×	0.005	LAMA4
regulation of cell adhesion	1	306.4×	0.005	LAMA4
regulation of cell migration	1	157.5×	0.008	LAMA4
cell adhesion	1	37.5×	0.027	LAMA4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

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
LAMA4	0	0
LAMA4-AS1	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	2	LAMA4, LAMA4-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LAMA4	0	—
LAMA4-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.