cardiomyopathy, dilated, 2D

Summary

cardiomyopathy, dilated, 2D (MONDO:0030300) is a disease caused by RPL3L (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RPL3L (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cardiomyopathy, dilated, 2D
Mondo ID	MONDO:0030300
OMIM	619371
DOID	DOID:0081160
UMLS	C5543535
MedGen	1782612
GARD	0025531
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 2D · CMD2D

Data availability: 17 ClinVar variants · 5 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 › cardiomyopathy, dilated, 2D

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 1JJ, dilated cardiomyopathy 1KK, left ventricular noncompaction 8, left ventricular noncompaction 10, dilated cardiomyopathy 1NN, 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

17 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 5 pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1162248	NM_005061.3(RPL3L):c.923A>T (p.Asp308Val)	RPL3L	Pathogenic	criteria provided, single submitter
1162249	NM_005061.3(RPL3L):c.1027C>T (p.Arg343Trp)	RPL3L	Pathogenic	no assertion criteria provided
1162250	NM_005061.3(RPL3L):c.566C>T (p.Thr189Met)	RPL3L	Pathogenic	no assertion criteria provided
1162253	NM_005061.3(RPL3L):c.481C>T (p.Arg161Trp)	RPL3L	Pathogenic	no assertion criteria provided
1162254	NM_005061.3(RPL3L):c.347G>A (p.Arg116His)	RPL3L	Pathogenic	no assertion criteria provided
4845737	NM_005061.3(RPL3L):c.523C>T (p.Gln175Ter)	RPL3L	Likely pathogenic	criteria provided, single submitter
1162252	NM_005061.3(RPL3L):c.80G>A (p.Gly27Asp)	RPL3L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1162251	NM_005061.3(RPL3L):c.922G>A (p.Asp308Asn)	RPL3L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1199411	NM_005061.3(RPL3L):c.1076_1080del (p.Ala359fs)	RPL3L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1802077	NM_005061.3(RPL3L):c.151G>A (p.Ala51Thr)	RPL3L	Uncertain significance	criteria provided, multiple submitters, no conflicts
2498271	NM_005061.3(RPL3L):c.829C>T (p.Arg277Cys)	RPL3L	Uncertain significance	criteria provided, multiple submitters, no conflicts
3062007	NM_005061.3(RPL3L):c.1202C>T (p.Pro401Leu)	RPL3L	Uncertain significance	criteria provided, single submitter
3065369	NM_005061.3(RPL3L):c.749_751del (p.Lys250_Val251delinsMet)	RPL3L	Uncertain significance	criteria provided, single submitter
3066154	NM_005061.3(RPL3L):c.808G>A (p.Gly270Arg)	RPL3L	Uncertain significance	criteria provided, multiple submitters, no conflicts
3254895	NM_005061.3(RPL3L):c.298C>T (p.Arg100Trp)	RPL3L	Uncertain significance	criteria provided, single submitter
3393141	NM_005061.3(RPL3L):c.692T>C (p.Val231Ala)	RPL3L	Uncertain significance	criteria provided, multiple submitters, no conflicts
4293620	NM_005061.3(RPL3L):c.964C>T (p.His322Tyr)	RPL3L	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
RPL3L	Strong	Autosomal recessive	cardiomyopathy, dilated, 2D	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPL3L	Orphanet:154	Familial isolated dilated cardiomyopathy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPL3L	HGNC:10351	ENSG00000140986	Q92901	Ribosomal protein uL3-like	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPL3L	Ribosomal protein uL3-like	Heart- and skeletal muscle-specific component of the ribosome, which regulates muscle function.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPL3L	Other/Unknown	no		Ribosomal_uL3, Transl_B-barrel_sf, Ribosomal_uL3_CS

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	1
skeletal muscle tissue of rectus abdominis	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPL3L	156	tissue_specific	marker	skeletal muscle tissue of rectus abdominis, hindlimb stylopod muscle, vastus lateralis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPL3L	4,559

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RPL3L	Q92901	94.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 1 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
Peptide chain elongation	1	126.9×	0.012	RPL3L
Viral mRNA Translation	1	126.9×	0.012	RPL3L
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	1	125.5×	0.012	RPL3L
Selenocysteine synthesis	1	120.2×	0.012	RPL3L
Eukaryotic Translation Termination	1	120.2×	0.012	RPL3L
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1	117.7×	0.012	RPL3L
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	1	117.7×	0.012	RPL3L
Formation of a pool of free 40S subunits	1	112.0×	0.012	RPL3L
Response of EIF2AK4 (GCN2) to amino acid deficiency	1	110.9×	0.012	RPL3L
Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	1	106.7×	0.012	RPL3L
L13a-mediated translational silencing of Ceruloplasmin expression	1	101.1×	0.012	RPL3L
SRP-dependent cotranslational protein targeting to membrane	1	100.2×	0.012	RPL3L
GTP hydrolysis and joining of the 60S ribosomal subunit	1	100.2×	0.012	RPL3L
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	1	97.6×	0.012	RPL3L
Regulation of expression of SLITs and ROBOs	1	69.2×	0.015	RPL3L
Major pathway of rRNA processing in the nucleolus and cytosol	1	61.7×	0.016	RPL3L

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
regulation of striated muscle tissue development	1	2808.7×	0.001	RPL3L
negative regulation of myotube differentiation	1	1123.5×	0.001	RPL3L
translation	1	102.8×	0.010	RPL3L

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
RPL3L	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	1	RPL3L

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)
RPL3L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.