cardiomyopathy, dilated, 2E

Summary

cardiomyopathy, dilated, 2E (MONDO:0030366) is a disease caused by JPH2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: JPH2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 71

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cardiomyopathy, dilated, 2E
Mondo ID	MONDO:0030366
OMIM	619492
DOID	DOID:0081161
UMLS	C5561970
MedGen	1794180
GARD	0025554
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 2E · CMD2E

Data availability: 71 ClinVar variants · 3 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, 2E

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, 2D, 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

71 retrieved; paginated sample, class counts are floors:

45 uncertain significance, 19 conflicting classifications of pathogenicity, 2 benign, 2 likely benign, 1 pathogenic, 1 benign/likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1205834	NM_020433.5(JPH2):c.1920dup (p.Glu641Ter)	JPH2	Pathogenic	no assertion criteria provided
4277386	NM_020433.5(JPH2):c.1836del (p.Glu613fs)	JPH2	Likely pathogenic	criteria provided, single submitter
1056674	NM_020433.5(JPH2):c.829G>T (p.Ala277Ser)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1189529	NM_020433.5(JPH2):c.1772G>T (p.Gly591Val)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1429402	NM_020433.5(JPH2):c.1753C>T (p.Pro585Ser)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1747780	NM_020433.5(JPH2):c.547C>G (p.Pro183Ala)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
188245	NM_020433.5(JPH2):c.1204G>A (p.Glu402Lys)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201797	NM_020433.5(JPH2):c.637C>T (p.Arg213Trp)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201804	NM_020433.5(JPH2):c.1896G>C (p.Glu632Asp)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225099	NM_020433.5(JPH2):c.692G>A (p.Arg231Gln)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
264361	NM_020433.5(JPH2):c.1357C>T (p.Pro453Ser)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
392762	NM_020433.5(JPH2):c.1433C>T (p.Pro478Leu)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
432626	NM_020433.5(JPH2):c.1852A>G (p.Thr618Ala)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
432736	NM_020433.5(JPH2):c.1292C>T (p.Pro431Leu)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
432845	NM_020433.5(JPH2):c.299C>T (p.Ser100Leu)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
454466	NM_020433.5(JPH2):c.1033G>C (p.Val345Leu)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
454469	NM_020433.5(JPH2):c.1394C>T (p.Pro465Leu)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
454470	NM_020433.5(JPH2):c.620A>G (p.Asn207Ser)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
488956	NM_020433.5(JPH2):c.424G>T (p.Gly142Ter)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
504867	NM_020433.5(JPH2):c.1894G>A (p.Glu632Lys)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
524943	NM_020433.5(JPH2):c.1461G>A (p.Pro487=)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1002787	NM_020433.5(JPH2):c.1732C>A (p.Pro578Thr)	JPH2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1009029	NM_020433.5(JPH2):c.949G>A (p.Glu317Lys)	JPH2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1014082	NM_020433.5(JPH2):c.1982C>A (p.Ala661Glu)	JPH2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034663	NM_020433.5(JPH2):c.2006_2010+1dup	JPH2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1044339	NM_020433.5(JPH2):c.1508A>G (p.Lys503Arg)	JPH2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1405421	NM_020433.5(JPH2):c.962A>G (p.Asn321Ser)	JPH2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1406792	NM_020433.5(JPH2):c.77A>G (p.His26Arg)	JPH2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1407323	NM_020433.5(JPH2):c.277C>T (p.Arg93Cys)	JPH2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1433376	NM_020433.5(JPH2):c.1577C>T (p.Pro526Leu)	JPH2	Uncertain significance	criteria provided, multiple submitters, no conflicts

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
JPH2	Strong	Autosomal recessive	cardiomyopathy, dilated, 2E	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
JPH2	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
JPH2	HGNC:14202	ENSG00000149596	Q9BR39	Junctophilin-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
JPH2	Junctophilin-2	Membrane-binding protein that provides a structural bridge between the plasma membrane and the sarcoplasmic reticulum and is required for normal excitation-contraction coupling in cardiomyocytes.

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)
JPH2	Other/Unknown	no		MORN, Junctophilin

Expression context

Cohort genes with no expression data: 0.

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
left ventricle myocardium	1
skeletal muscle tissue of rectus abdominis	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
JPH2	173	broad	yes	left ventricle myocardium, skeletal muscle tissue of rectus abdominis, tibialis anterior

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
JPH2	1,278

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
JPH2	Q9BR39	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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 cardiac muscle tissue development	1	16852.0×	2e-04	JPH2
obsolete positive regulation of ryanodine-sensitive calcium-release channel activity	1	16852.0×	2e-04	JPH2
regulation of cardiac muscle contraction by calcium ion signaling	1	1296.3×	0.001	JPH2
calcium ion transport into cytosol	1	1203.7×	0.001	JPH2
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	674.1×	0.002	JPH2
calcium ion homeostasis	1	443.5×	0.002	JPH2

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
JPH2	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	JPH2

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)
JPH2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.