dilated cardiomyopathy 1M

Summary

dilated cardiomyopathy 1M (MONDO:0011840) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 380

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1M
Mondo ID	MONDO:0011840
MeSH	C564390
OMIM	607482
DOID	DOID:0110449
UMLS	C1843808
MedGen	334498
GARD	0015413
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 1M · cardiomyopathy, dilated, type 1M · CMD1M · CSRP3 familial isolated dilated cardiomyopathy · dilated cardiomyopathy type 1M · familial isolated dilated cardiomyopathy caused by mutation in CSRP3

Data availability: 380 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 › dilated cardiomyopathy › familial dilated cardiomyopathy › familial isolated dilated cardiomyopathy › dilated cardiomyopathy 1M

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 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 1JJ, 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

380 retrieved; paginated sample, class counts are floors:

204 uncertain significance, 107 likely benign, 32 conflicting classifications of pathogenicity, 20 pathogenic, 8 benign/likely benign, 5 likely pathogenic, 3 pathogenic/likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1008253	NM_003476.5(CSRP3):c.377C>G (p.Ser126Ter)	CSRP3	Pathogenic	criteria provided, single submitter
1009234	NM_003476.5(CSRP3):c.49_55del (p.Val17fs)	CSRP3	Pathogenic	criteria provided, single submitter
1011003	NM_003476.5(CSRP3):c.72del (p.Gln24fs)	CSRP3	Pathogenic	criteria provided, single submitter
1324182	NM_003476.5(CSRP3):c.50_51insGCAGATTTCTT (p.Tyr18fs)	CSRP3	Pathogenic	criteria provided, multiple submitters, no conflicts
1418855	NM_003476.5(CSRP3):c.82_85del (p.Arg28fs)	CSRP3	Pathogenic	criteria provided, single submitter
1470431	NM_003476.5(CSRP3):c.165del (p.Ile56fs)	CSRP3	Pathogenic	criteria provided, single submitter
216572	NM_003476.5(CSRP3):c.337A>T (p.Lys113Ter)	CSRP3	Pathogenic	criteria provided, single submitter
219444	NM_003476.5(CSRP3):c.449G>A (p.Cys150Tyr)	CSRP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2932324	NM_003476.5(CSRP3):c.186T>G (p.Tyr62Ter)	CSRP3	Pathogenic	criteria provided, single submitter
2951005	NM_003476.5(CSRP3):c.279del (p.Gln93fs)	CSRP3	Pathogenic	criteria provided, single submitter
3244681	NC_000011.9:g.(?18418390)(19213995_?)del	CSRP3	Pathogenic	criteria provided, single submitter
372584	NM_003476.5(CSRP3):c.364C>T (p.Arg122Ter)	CSRP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3752686	NM_003476.5(CSRP3):c.444dup (p.Ile149fs)	CSRP3	Pathogenic	criteria provided, single submitter
3755823	NM_003476.5(CSRP3):c.304del (p.Val102fs)	CSRP3	Pathogenic	criteria provided, single submitter
3759643	NM_003476.5(CSRP3):c.54C>A (p.Tyr18Ter)	CSRP3	Pathogenic	criteria provided, single submitter
3764079	NM_003476.5(CSRP3):c.27del (p.Lys9fs)	CSRP3	Pathogenic	criteria provided, single submitter
4784477	NM_003476.5(CSRP3):c.161C>A (p.Ser54Ter)	CSRP3	Pathogenic	criteria provided, single submitter
4786672	NM_003476.5(CSRP3):c.298del (p.Arg100fs)	CSRP3	Pathogenic	criteria provided, single submitter
543041	NM_003476.5(CSRP3):c.55del (p.His19fs)	CSRP3	Pathogenic	criteria provided, single submitter
543042	NM_003476.5(CSRP3):c.373A>T (p.Lys125Ter)	CSRP3	Pathogenic	criteria provided, single submitter
655718	NM_003476.5(CSRP3):c.52del (p.Tyr18fs)	CSRP3	Pathogenic	criteria provided, single submitter
8777	NM_003476.5(CSRP3):c.172T>G (p.Cys58Gly)	CSRP3	Pathogenic	criteria provided, multiple submitters, no conflicts
915721	NM_003476.5(CSRP3):c.111C>A (p.Cys37Ter)	CSRP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2941886	NM_003476.5(CSRP3):c.281+2T>C	CSRP3	Likely pathogenic	criteria provided, single submitter
2947685	NM_003476.5(CSRP3):c.414+1G>A	CSRP3	Likely pathogenic	criteria provided, single submitter
3763020	NM_003476.5(CSRP3):c.414+1G>C	CSRP3	Likely pathogenic	criteria provided, single submitter
4791293	NM_003476.5(CSRP3):c.281+1G>C	CSRP3	Likely pathogenic	criteria provided, single submitter
915578	NM_003476.5(CSRP3):c.414+1G>T	CSRP3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1204953	NM_003476.5(CSRP3):c.415-1G>T	CSRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1284733	NM_003476.5(CSRP3):c.286_287del (p.Pro96fs)	CSRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
CSRP3	Strong	Autosomal dominant	hypertrophic cardiomyopathy 12	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CSRP3	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
CSRP3	HGNC:2472	ENSG00000129170	P50461	Cysteine and glycine-rich protein 3	gencc,clinvar
LDHAL6A	HGNC:28335	ENSG00000166800	Q6ZMR3	L-lactate dehydrogenase A-like 6A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CSRP3	Cysteine and glycine-rich protein 3	Positive regulator of myogenesis.
LDHAL6A	L-lactate dehydrogenase A-like 6A	Catalyzes the interconversion of L-lactate and pyruvate with nicotinamide adenine dinucleotide NAD(+) as a coenzyme.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CSRP3	Transcription factor	no		Znf_LIM
LDHAL6A	Other/Unknown	no		Lactate/malate_DH_N, L-lactate/malate_DH, L-lactate_DH

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
heart right ventricle	1
left ventricle myocardium	1
skeletal muscle tissue of rectus abdominis	1
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CSRP3	173	tissue_specific	marker	skeletal muscle tissue of rectus abdominis, heart right ventricle, left ventricle myocardium
LDHAL6A	134	tissue_specific	yes	secondary oocyte, oocyte, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LDHAL6A	3,097
CSRP3	1,376

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CSRP3	P50461	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LDHAL6A	Q6ZMR3	95.39

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Pyruvate metabolism	1	407.9×	0.007	LDHAL6A
Aerobic respiration and respiratory electron transport	1	88.5×	0.017	LDHAL6A
Metabolism	1	11.6×	0.086	LDHAL6A

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
positive regulation of actin filament severing	1	8426.0×	0.003	CSRP3
negative regulation of actin filament severing	1	4213.0×	0.003	CSRP3
muscle tissue development	1	1685.2×	0.003	CSRP3
T-tubule organization	1	1404.3×	0.003	CSRP3
phospholipase C/protein kinase C signal transduction	1	1404.3×	0.003	CSRP3
detection of muscle stretch	1	1203.7×	0.003	CSRP3
pyruvate catabolic process	1	1053.2×	0.003	LDHAL6A
lactate metabolic process	1	936.2×	0.003	LDHAL6A
establishment of protein localization to organelle	1	936.2×	0.003	CSRP3
cardiac muscle hypertrophy	1	842.6×	0.003	CSRP3
cardiac myofibril assembly	1	648.1×	0.004	CSRP3
regulation of the force of heart contraction	1	495.6×	0.004	CSRP3
cardiac muscle tissue development	1	443.5×	0.004	CSRP3
muscle cell cellular homeostasis	1	324.1×	0.005	CSRP3
regulation of protein localization to plasma membrane	1	324.1×	0.005	CSRP3
negative regulation of myoblast differentiation	1	312.1×	0.005	CSRP3
cardiac muscle contraction	1	200.6×	0.007	CSRP3
sarcomere organization	1	191.5×	0.007	CSRP3
positive regulation of myoblast differentiation	1	183.2×	0.007	CSRP3
skeletal muscle tissue development	1	145.3×	0.009	CSRP3
insulin receptor signaling pathway	1	110.9×	0.011	CSRP3
intracellular calcium ion homeostasis	1	72.6×	0.016	CSRP3
glucose homeostasis	1	65.3×	0.017	CSRP3
inflammatory response	1	18.9×	0.055	CSRP3
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	CSRP3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CSRP3	0	0
LDHAL6A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	CSRP3, LDHAL6A

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)
CSRP3	0	—
LDHAL6A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.