JPH2 (Junctophilin-2)
A key regulator of cardiac and skeletal muscle calcium handling, implicated in hypertrophic cardiomyopathy and arrhythmias.
Gene Information Card
| Symbol | JPH2 |
|---|---|
| Full Name | Junctophilin 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.12 |
| NCBI Gene ID | 57158 ncbi.nlm.nih.gov/gene/57158 |
| Ensembl ID | ENSG00000149596 |
| UniProt ID | Q9BR39 |
| OMIM ID | 605267 |
| HGNC ID | 14202 |
| Aliases | JP-2, JP2, CMD1V, CMH17 |
Description
JPH2 encodes junctophilin-2, a component of the junctional membrane complex in cardiac and skeletal muscle. It stabilizes the close apposition of the sarcoplasmic reticulum and T-tubules, essential for efficient excitation-contraction coupling and calcium-induced calcium release. Mutations in JPH2 are associated with hypertrophic cardiomyopathy (CMH17) and dilated cardiomyopathy (CMD1V).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypertrophic Cardiomyopathy 17 (CMH17) | Missense mutations disrupt junctophilin-2 structure, impairing T-tubule organization and calcium handling, leading to myocyte hypertrophy and diastolic dysfunction. | OMIM #613873; ClinVar |
| Dilated Cardiomyopathy 1V (CMD1V) | Loss-of-function variants reduce junctophilin-2 expression, causing T-tubule remodeling and decreased contractility. | OMIM #613874; ClinVar |
| Cardiac Arrhythmia | Altered calcium dynamics due to JPH2 mutations predispose to ventricular arrhythmias and sudden cardiac death. | PubMed studies; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 28.5 | High |
| Skeletal Muscle | 15.2 | Medium |
| Brain | 0.8 | Low |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPSC-derived) | 30.1 | High expression; used in functional studies |
| Skeletal muscle myotubes | 18.7 | Medium expression |
| HEK293 | 0.2 | Low; not endogenous |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.184G>A (p.Gly62Ser) | Missense | Rare | Alters junctophilin-2 membrane orientation; associated with HCM |
| c.428C>T (p.Thr143Ile) | Missense | Rare | Impairs T-tubule formation; linked to DCM |
| c.1123G>A (p.Gly375Arg) | Missense | Rare | Disrupts MORN domain; pathogenic in HCM |
Mutation functional classification
Loss of Function (LOF)
Nonsense or frameshift variants leading to haploinsufficiency; observed in DCM.
Gain of Function (GOF)
Not well documented; some missense variants may alter calcium sensitivity.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly62Ser) that disrupt protein-protein interactions and T-tubule structure.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum (GO:0005783) | • T-tubule (GO:0030315) |
| • sarcoplasmic reticulum (GO:0016529) | • relaxation of cardiac muscle (GO:0055119) |
| • cardiac muscle cell contraction (GO:0086003) |
Pathways
• Excitation-contraction coupling (Reactome R-HSA-5576892)
• Calcium signaling pathway (KEGG hsa04020)
• Cardiac muscle contraction (KEGG hsa04260)
Protein Summary
Junctophilin-2 is a 696-amino acid protein with a C-terminal transmembrane domain anchoring it to the sarcoplasmic reticulum and N-terminal MORN repeats that bind the plasma membrane/T-tubule. It forms a structural bridge essential for the dyad junction, enabling efficient calcium release from the sarcoplasmic reticulum via ryanodine receptors. Reduced expression or mutation leads to T-tubule disorganization and impaired cardiac contractility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| JPH2 Knockout HEK293 Cell Line | EDJ-KQ13882 | Human | 57158 | Details Get a Quote |
| JPH2 Knockout A-549 Cell Line | EDJ-KQ43736 | Human | 57158 | Details Get a Quote |
| JPH2 Knockout HeLa Cell Line | EDJ-KQ43737 | Human | 57158 | Details Get a Quote |
| JPH2 Knockout HCT 116 Cell Line | EDJ-KQ73761 | Human | 57158 | Details Get a Quote |
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