dilated cardiomyopathy 1DD

Summary

dilated cardiomyopathy 1DD (MONDO:0013168) is a disease caused by RBM20 (GenCC Definitive), with 4 cohort genes.

At a glance

• Causal gene: RBM20 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 1,963

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1DD
Mondo ID	MONDO:0013168
MeSH	C567725
OMIM	613172
DOID	DOID:0110447
UMLS	C2750995
MedGen	416441
GARD	0015627
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 1DD · cardiomyopathy, dilated, type 1Dd · CMD1DD · dilated cardiomyopathy type 1DD · familial isolated dilated cardiomyopathy caused by mutation in RBM20 · RBM20 familial isolated dilated cardiomyopathy

Data availability: 1,963 ClinVar variants · 4 GenCC gene-disease records · 5 cell lines.

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 1DD

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 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

600 retrieved; paginated sample, class counts are floors:

228 uncertain significance, 211 likely benign, 132 conflicting classifications of pathogenicity, 14 benign/likely benign, 8 pathogenic, 3 benign, 3 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1163332	NM_001134363.3(RBM20):c.460C>T (p.Gln154Ter)	RBM20	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1345980	NM_001134363.3(RBM20):c.522del (p.Ser175fs)	RBM20	Pathogenic	criteria provided, single submitter
1399883	NM_001134363.3(RBM20):c.1990_2000del (p.Gly663_Pro664insTer)	RBM20	Pathogenic	criteria provided, single submitter
1493612	NM_001134363.3(RBM20):c.1590C>A (p.Cys530Ter)	RBM20	Pathogenic	criteria provided, single submitter
1703676	GRCh37/hg19 10q25.2(chr10:112516278-112591134)	RBM20	Pathogenic	no assertion criteria provided
1934853	NM_001134363.3(RBM20):c.2566C>T (p.Gln856Ter)	RBM20	Pathogenic	criteria provided, single submitter
1965699	NM_001134363.3(RBM20):c.277C>T (p.Gln93Ter)	RBM20	Pathogenic	criteria provided, single submitter
1973169	NM_001134363.3(RBM20):c.1070C>A (p.Ser357Ter)	RBM20	Pathogenic	criteria provided, single submitter
1990792	NM_001134363.3(RBM20):c.514dup (p.Ser172fs)	RBM20	Pathogenic	criteria provided, single submitter
1345506	NM_001134363.3(RBM20):c.2550+1G>A	RBM20	Likely pathogenic	criteria provided, single submitter
1522677	NM_001134363.3(RBM20):c.1429+1G>A	RBM20	Likely pathogenic	criteria provided, single submitter
1527870	NM_001134363.3(RBM20):c.1385del (p.Ala462fs)	RBM20	Likely pathogenic	criteria provided, single submitter
1000012	NM_001134363.3(RBM20):c.1349G>A (p.Arg450Gln)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000712	NM_001134363.3(RBM20):c.1175G>A (p.Arg392Gln)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000718	NM_001134363.3(RBM20):c.1384G>A (p.Ala462Thr)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1001438	NM_001134363.3(RBM20):c.1078A>G (p.Thr360Ala)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1002521	NM_001134363.3(RBM20):c.132_149dup (p.44PPPPPQ[3])	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1003343	NM_001134363.3(RBM20):c.2063G>A (p.Arg688Gln)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1007583	NM_001134363.3(RBM20):c.3169C>G (p.Arg1057Gly)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1007670	NM_001134363.3(RBM20):c.1027C>G (p.His343Asp)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1011000	NM_001134363.3(RBM20):c.1396A>G (p.Ser466Gly)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1011219	NM_001134363.3(RBM20):c.3262C>A (p.Pro1088Thr)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1011868	NM_001134363.3(RBM20):c.1868G>A (p.Arg623Gln)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1012558	NM_001134363.3(RBM20):c.3661C>T (p.Arg1221Cys)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1015078	NM_001134363.3(RBM20):c.2239C>T (p.His747Tyr)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1017418	NM_001134363.3(RBM20):c.883G>A (p.Gly295Arg)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1017919	NM_001134363.3(RBM20):c.3489C>A (p.Cys1163Ter)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1019293	NM_001134363.3(RBM20):c.25C>T (p.Gln9Ter)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1023169	NM_001134363.3(RBM20):c.3217G>A (p.Glu1073Lys)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1023204	NM_001134363.3(RBM20):c.3124A>G (p.Thr1042Ala)	RBM20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 5 · 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
RBM20	Definitive	Autosomal dominant	dilated cardiomyopathy	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RBM20	Orphanet:154	Familial isolated dilated cardiomyopathy
TNNT2	Orphanet:154	Familial isolated dilated cardiomyopathy
TNNT2	Orphanet:54260	Left ventricular noncompaction
TNNT2	Orphanet:75249	Familial isolated restrictive cardiomyopathy
BBIP1	Orphanet:110	Bardet-Biedl syndrome

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
RBM20	HGNC:27424	ENSG00000203867	Q5T481	RNA-binding protein 20	gencc,clinvar
TNNT2	HGNC:11949	ENSG00000118194	P45379	Troponin T, cardiac muscle	clinvar
BBIP1	HGNC:28093	ENSG00000214413	A8MTZ0	BBSome-interacting protein 1	clinvar
PDCD4	HGNC:8763	ENSG00000150593	Q53EL6	Programmed cell death protein 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RBM20	RNA-binding protein 20	RNA-binding protein that acts as a regulator of mRNA splicing of a subset of genes encoding key structural proteins involved in cardiac development, such as TTN (Titin), CACNA1C, CAMK2D or PDLIM5/ENH.
TNNT2	Troponin T, cardiac muscle	Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
BBIP1	BBSome-interacting protein 1	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
PDCD4	Programmed cell death protein 4	Inhibits translation initiation and cap-dependent translation.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 3 · 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	2.1×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RBM20	Transcription factor	no		RRM_dom, Matrin/U1-C_Znf_C2H2, Matrin/U1-like-C_Znf_C2H2
TNNT2	Other/Unknown	no		Troponin, TNNT, Troponin_sf
BBIP1	Other/Unknown	no		BBIP10
PDCD4	Other/Unknown	no		Initiation_fac_eIF4g_MI, ARM-type_fold, PDCD4

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
cardiac muscle of right atrium	1
left ventricle myocardium	1
myocardium	1
apex of heart	1
cardiac atrium	1
right atrium auricular region	1
buccal mucosa cell	1
epithelium of nasopharynx	1
sperm	1
body of pancreas	1
skin of abdomen	1
skin of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RBM20	191	broad	marker	left ventricle myocardium, cardiac muscle of right atrium, myocardium
TNNT2	154	broad	marker	apex of heart, right atrium auricular region, cardiac atrium
BBIP1	288	ubiquitous	marker	epithelium of nasopharynx, buccal mucosa cell, sperm
PDCD4	296	ubiquitous	marker	body of pancreas, skin of abdomen, skin of leg

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDCD4	2,383
TNNT2	1,944
RBM20	1,225
BBIP1	29

Intra-cohort edges

A	B	Sources
RBM20	TNNT2	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNNT2	P45379	25
PDCD4	Q53EL6	11
BBIP1	A8MTZ0	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RBM20	Q5T481	48.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
BBSome-mediated cargo-targeting to cilium	1	165.5×	0.018	BBIP1
Striated Muscle Contraction	1	102.9×	0.018	TNNT2
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	100.2×	0.018	PDCD4
Cargo trafficking to the periciliary membrane	1	82.8×	0.018	BBIP1
Cilium Assembly	1	36.2×	0.033	BBIP1
Organelle biogenesis and maintenance	1	22.0×	0.045	BBIP1

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
epithelial to mesenchymal transition involved in cardiac fibroblast development	1	2106.5×	0.008	PDCD4
negative regulation of myofibroblast differentiation	1	1053.2×	0.008	PDCD4
heart formation	1	842.6×	0.008	RBM20
receptor localization to non-motile cilium	1	842.6×	0.008	BBIP1
spliceosome-depend formation of circular RNA	1	842.6×	0.008	RBM20
negative regulation of vascular associated smooth muscle cell differentiation	1	842.6×	0.008	PDCD4
negative regulation of JUN kinase activity	1	601.9×	0.009	PDCD4
positive regulation of vascular associated smooth muscle cell apoptotic process	1	526.6×	0.009	PDCD4
regulation of muscle contraction	1	421.3×	0.009	TNNT2
negative regulation of ATP-dependent activity	1	421.3×	0.009	TNNT2
positive regulation of ATP-dependent activity	1	351.1×	0.010	TNNT2
erythrocyte homeostasis	1	324.1×	0.010	BBIP1
muscle filament sliding	1	263.3×	0.010	TNNT2
positive regulation of RNA splicing	1	263.3×	0.010	RBM20
regulation of mRNA splicing, via spliceosome	1	221.7×	0.011	RBM20
negative regulation of mRNA splicing, via spliceosome	1	191.5×	0.012	RBM20
positive regulation of endothelial cell apoptotic process	1	183.2×	0.012	PDCD4
ventricular cardiac muscle tissue morphogenesis	1	175.5×	0.012	TNNT2
negative regulation of vascular associated smooth muscle cell proliferation	1	168.5×	0.012	PDCD4
eating behavior	1	150.5×	0.013	BBIP1
B cell homeostasis	1	140.4×	0.013	BBIP1
regulation of heart contraction	1	123.9×	0.014	TNNT2
negative regulation of cytokine production involved in inflammatory response	1	105.3×	0.016	PDCD4
cardiac muscle contraction	1	100.3×	0.016	TNNT2
sarcomere organization	1	95.8×	0.016	TNNT2
response to calcium ion	1	79.5×	0.018	TNNT2
positive regulation of non-canonical NF-kappaB signal transduction	1	63.8×	0.022	PDCD4
regulation of alternative mRNA splicing, via spliceosome	1	61.1×	0.022	RBM20
regulation of RNA splicing	1	54.7×	0.024	RBM20
BMP signaling pathway	1	50.1×	0.025	PDCD4

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PDCD4	SIROLIMUS

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDCD4	1	4
RBM20	0	0
TNNT2	0	0
BBIP1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SIROLIMUS	4	PDCD4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PDCD4	8	Binding:8
TNNT2	2	Binding:2

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

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)
SIROLIMUS	4	PDCD4

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PDCD4
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	3	RBM20, TNNT2, BBIP1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RBM20	0	—
TNNT2	2	—
BBIP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.