Hypertrophic cardiomyopathy 17

Summary

Hypertrophic cardiomyopathy 17 (MONDO:0013474) 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: 96

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertrophic cardiomyopathy 17
Mondo ID	MONDO:0013474
OMIM	613873
DOID	DOID:0110323
UMLS	C3151264
MedGen	462614
GARD	0024929
Is cancer (heuristic)	no

Also known as: cardiomyopathy, familial hypertrophic, 17 · cardiomyopathy, familial hypertrophic, type 17 · cardiomyopathy, hypertrophic, 17 · CMH17 · hypertrophic cardiomyopathy caused by mutation in JPH2 · hypertrophic cardiomyopathy type 17 · JPH2 hypertrophic cardiomyopathy

Data availability: 96 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 › hypertrophic cardiomyopathy › familial hypertrophic cardiomyopathy › hypertrophic cardiomyopathy 17

Related subtypes (39): hypertrophic cardiomyopathy 2, hypertrophic cardiomyopathy 3, hypertrophic cardiomyopathy 4, Beckwith-Wiedemann syndrome, myotonic dystrophy type 1, hypertrophic cardiomyopathy 1, very long chain acyl-CoA dehydrogenase deficiency, multiple acyl-CoA dehydrogenase deficiency, 46,XY complete gonadal dysgenesis, hypertrophic cardiomyopathy 6, dilated cardiomyopathy 1C, hypertrophic cardiomyopathy 25, hypertrophic cardiomyopathy 8, hypertrophic cardiomyopathy 10, long chain 3-hydroxyacyl-CoA dehydrogenase deficiency, cardiomyopathy-hypotonia-lactic acidosis syndrome, hypertrophic cardiomyopathy 11, hypertrophic cardiomyopathy 12, hypertrophic cardiomyopathy 13, hypertrophic cardiomyopathy 14, hypertrophic cardiomyopathy 15, hypertrophic cardiomyopathy 7, hypertrophic cardiomyopathy 9, hypertrophic cardiomyopathy 16, hypertrophic cardiomyopathy 18, hypertrophic cardiomyopathy 19, hypertrophic cardiomyopathy 20, hypertrophic cardiomyopathy 21, dilated cardiomyopathy 1KK, hypertrophic cardiomyopathy 26, Noonan syndrome and Noonan-related syndrome, long chain acyl-CoA dehydrogenase deficiency, cardiomyopathy, familial hypertrophic, 28, cardiomyopathy, familial hypertrophic 27, cardiomyopathy, familial hypertrophic, 23, with or without ventricular noncompaction, cardiomyopathy, familial restrictive, 5, cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies, cardiomyopathy, familial hypertrophic, 30, atrial, cardiomyopathy, familial hypertrophic, 31

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

96 retrieved; paginated sample, class counts are floors:

46 uncertain significance, 27 conflicting classifications of pathogenicity, 7 benign, 7 benign/likely benign, 5 likely benign, 3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
30455	NM_020433.5(JPH2):c.301A>C (p.Ser101Arg)	JPH2	Pathogenic	no assertion criteria provided
30457	NM_020433.5(JPH2):c.494C>T (p.Ser165Phe)	JPH2	Pathogenic	no assertion criteria provided
4813523	NM_020433.5(JPH2):c.107del (p.Gly36fs)	JPH2	Pathogenic	criteria provided, single submitter
829986	NM_020433.5(JPH2):c.191G>A (p.Trp64Ter)	JPH2	Likely pathogenic	no assertion criteria provided
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
1324604	NM_020433.5(JPH2):c.505G>A (p.Glu169Lys)	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
197322	NM_020433.5(JPH2):c.1380G>A (p.Ala460=)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201792	NM_020433.5(JPH2):c.128A>G (p.Asn43Ser)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201795	NM_020433.5(JPH2):c.458T>C (p.Val153Ala)	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
201798	NM_020433.5(JPH2):c.661T>C (p.Phe221Leu)	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
30456	NM_020433.5(JPH2):c.421T>C (p.Tyr141His)	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
403849	NM_020433.5(JPH2):c.1658C>T (p.Ala553Val)	JPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
429669	NM_020433.5(JPH2):c.838G>A (p.Glu280Lys)	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
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

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.