dilated cardiomyopathy 1C

Summary

dilated cardiomyopathy 1C (MONDO:0011094) is a disease caused by LDB3 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: LDB3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 145

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1C
Mondo ID	MONDO:0011094
MeSH	C563307
OMIM	601493
DOID	DOID:0110423
NCIT	C170436
UMLS	C1832244
MedGen	316944
GARD	0015331
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 1C, with or without left ventricular noncompaction · cardiomyopathy, dilated, 1C, with or without LVNC · cardiomyopathy, hypertrophic, 24 · CMD1C · dilated cardiomyopathy type 1C

Data availability: 145 ClinVar variants · 2 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 › left ventricular noncompaction › dilated cardiomyopathy 1C

Related subtypes (12): dilated cardiomyopathy 1D, left ventricular noncompaction 1, left ventricular noncompaction 2, dilated cardiomyopathy 1Y, dilated cardiomyopathy 1R, dilated cardiomyopathy 1S, left ventricular noncompaction 7, left ventricular noncompaction 8, left ventricular noncompaction 10, left ventricular noncompaction 9, left ventricular noncompaction 4, left ventricular noncompaction 5

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

145 retrieved; paginated sample, class counts are floors:

80 uncertain significance, 34 conflicting classifications of pathogenicity, 13 benign/likely benign, 7 likely benign, 6 benign, 2 pathogenic/likely pathogenic, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4727	NM_001368067.1(LDB3):c.439G>A (p.Ala147Thr)	LDB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4728	NM_001368067.1(LDB3):c.494C>T (p.Ala165Val)	LDB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
997776	NM_007078.3(LDB3):c.1723T>A (p.Phe575Ile)	LDB3	Pathogenic	no assertion criteria provided
997777	NM_007078.3(LDB3):c.1818T>A (p.Phe606Leu)	LDB3	Pathogenic	no assertion criteria provided
997774	NM_007078.3(LDB3):c.718G>A (p.Asp240Asn)	LDB3	Likely pathogenic	no assertion criteria provided
1002404	NM_007078.3(LDB3):c.2037C>T (p.Gly679=)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1433678	NM_007078.3(LDB3):c.1618G>T (p.Glu540Ter)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1490672	NM_007078.3(LDB3):c.1565C>T (p.Thr522Ile)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
163829	NM_007078.3(LDB3):c.655C>T (p.Arg219Ter)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
163853	NM_007078.3(LDB3):c.1798C>T (p.Arg600Ter)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191695	NM_007078.3(LDB3):c.443G>A (p.Arg148Gln)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191697	NM_007078.3(LDB3):c.715G>A (p.Val239Ile)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201835	NM_007078.3(LDB3):c.328G>A (p.Ala110Thr)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201843	NM_007078.3(LDB3):c.794G>A (p.Arg265His)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201849	NM_007078.3(LDB3):c.1487T>C (p.Phe496Ser)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201850	NM_007078.3(LDB3):c.1567C>G (p.Pro523Ala)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201856	NM_007078.3(LDB3):c.54G>T (p.Gln18His)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227498	NM_007078.3(LDB3):c.668C>T (p.Ser223Leu)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
235003	NM_007078.3(LDB3):c.550A>G (p.Lys184Glu)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
240719	NM_007078.3(LDB3):c.1851T>C (p.Ile617=)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
279835	NM_007078.3(LDB3):c.1225C>A (p.Gln409Lys)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301332	NM_007078.3(LDB3):c.30C>G (p.Pro10=)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301336	NM_007078.3(LDB3):c.723C>T (p.Ser241=)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301342	NM_007078.3(LDB3):c.897-6707G>A	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
36446	NM_007078.3(LDB3):c.2092G>A (p.Ala698Thr)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
406804	NM_007078.3(LDB3):c.886C>T (p.Arg296Ter)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
45527	NM_007078.3(LDB3):c.1535A>C (p.Gln512Pro)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
45551	NM_007078.3(LDB3):c.664G>A (p.Ala222Thr)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
45555	NM_007078.3(LDB3):c.793C>T (p.Arg265Cys)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4729	NM_001368067.1(LDB3):c.802C>T (p.Arg268Cys)	LDB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 10 · 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
LDB3	Strong	Autosomal recessive	cardiomyopathy, dilated, 2l	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LDB3	Orphanet:154	Familial isolated dilated cardiomyopathy
LDB3	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
LDB3	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
LDB3	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
LDB3	Orphanet:54260	Left ventricular noncompaction
LDB3	Orphanet:98912	Late-onset distal myopathy, Markesbery-Griggs type
RYR2	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
RYR2	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
RYR2	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
RYR2	Orphanet:3286	Catecholaminergic polymorphic ventricular tachycardia

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
LDB3	HGNC:15710	ENSG00000122367	O75112	LIM domain-binding protein 3	gencc,clinvar
RYR2	HGNC:10484	ENSG00000198626	Q92736	Ryanodine receptor 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LDB3	LIM domain-binding protein 3	May function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton.
RYR2	Ryanodine receptor 2	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · 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
Ion channel	1	55.8×	0.036
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LDB3	Transcription factor	no		PDZ, Znf_LIM, Zasp-like_motif
RYR2	Ion channel	yes		RIH_dom, B30.2/SPRY, EF_hand_dom

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
apex of heart	1
hindlimb stylopod muscle	1
skeletal muscle tissue of biceps brachii	1
heart right ventricle	1
left ventricle myocardium	1
myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LDB3	247	broad	marker	skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle, apex of heart
RYR2	210	broad	marker	heart right ventricle, left ventricle myocardium, myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RYR2	2,653
LDB3	1,275

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RYR2	Q92736	26
LDB3	O75112	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Ion homeostasis	1	203.9×	0.016	RYR2
Stimuli-sensing channels	1	135.9×	0.016	RYR2
Cardiac conduction	1	108.8×	0.016	RYR2
Ion channel transport	1	96.0×	0.016	RYR2
Muscle contraction	1	77.2×	0.016	RYR2
Transport of small molecules	1	25.1×	0.040	RYR2

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
establishment of protein localization to endoplasmic reticulum	1	8426.0×	0.003	RYR2
Purkinje myocyte to ventricular cardiac muscle cell signaling	1	4213.0×	0.003	RYR2
type B pancreatic cell apoptotic process	1	2808.7×	0.003	RYR2
regulation of AV node cell action potential	1	2808.7×	0.003	RYR2
regulation of atrial cardiac muscle cell action potential	1	2808.7×	0.003	RYR2
left ventricular cardiac muscle tissue morphogenesis	1	2106.5×	0.003	RYR2
obsolete positive regulation of sequestering of calcium ion	1	2106.5×	0.003	RYR2
sarcoplasmic reticulum calcium ion transport	1	1685.2×	0.003	RYR2
positive regulation of the force of heart contraction	1	1685.2×	0.003	RYR2
regulation of SA node cell action potential	1	1404.3×	0.003	RYR2
response to caffeine	1	1203.7×	0.003	RYR2
embryonic heart tube morphogenesis	1	936.2×	0.003	RYR2
cardiac muscle hypertrophy	1	842.6×	0.003	RYR2
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	842.6×	0.003	RYR2
cellular response to caffeine	1	766.0×	0.003	RYR2
muscle structure development	1	702.2×	0.003	LDB3
cell communication by electrical coupling involved in cardiac conduction	1	702.2×	0.003	RYR2
regulation of ventricular cardiac muscle cell action potential	1	702.2×	0.003	RYR2
regulation of cardiac muscle contraction by calcium ion signaling	1	648.1×	0.003	RYR2
response to redox state	1	648.1×	0.003	RYR2
cellular response to epinephrine stimulus	1	648.1×	0.003	RYR2
calcium ion transport into cytosol	1	601.9×	0.003	RYR2
detection of calcium ion	1	561.7×	0.003	RYR2
ventricular cardiac muscle cell action potential	1	495.6×	0.004	RYR2
regulation of cardiac muscle contraction	1	443.5×	0.004	RYR2
striated muscle contraction	1	421.3×	0.004	RYR2
response to muscle stretch	1	383.0×	0.004	RYR2
positive regulation of heart rate	1	351.1×	0.004	RYR2
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	1	337.0×	0.004	RYR2
response to muscle activity	1	290.6×	0.005	RYR2

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
RYR2	1	2
LDB3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ALADORIAN	2	RYR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RYR2	15	Binding:15

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)
ALADORIAN	2	RYR2

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	RYR2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	LDB3

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)
LDB3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.