JPH4 Gene - Junctophilin 4
A key component of junctional membrane complexes in excitable cells
Gene Information Card
| Symbol | JPH4 |
|---|---|
| Full Name | junctophilin 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q11.2 |
| NCBI Gene ID | 84502 ncbi.nlm.nih.gov/gene/84502 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | Q96JJ6 |
| OMIM ID | 609269 |
| HGNC ID | 18797 |
| Aliases | JP4, JPHL, JPH4A, JPH4B |
Description
JPH4 encodes junctophilin 4, a member of the junctophilin family that forms junctional membrane complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum. These complexes are critical for calcium signaling in excitable cells, particularly in neurons and cardiac muscle. JPH4 is involved in the structural organization of calcium release units and modulates excitation-contraction coupling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability | Disruption of calcium signaling at neuronal junctions | ClinVar: pathogenic variants in JPH4 associated with neurodevelopmental disorders |
| Epileptic encephalopathy | Impaired synaptic calcium homeostasis due to JPH4 loss-of-function | ClinVar: de novo missense variants reported in patients with early-onset seizures |
| Cardiac arrhythmia | Altered excitation-contraction coupling in cardiomyocytes | OMIM: rare variants linked to arrhythmia susceptibility |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Skeletal muscle | 6.1 | Low |
| Testis | 4.2 | Low |
| Lung | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.2 | Neuronal cell line; high expression |
| U-87 MG | 9.8 | Glioblastoma cell line; moderate expression |
| HEK 293 | 2.1 | Low expression |
| K562 | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | Rare | Reduced protein stability; loss of function |
| c.457G>A (p.Gly153Arg) | Missense | Rare | Impaired membrane targeting; dominant negative effect |
| c.712_713del (p.Leu238fs) | Frameshift | Very rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations lead to truncated protein lacking transmembrane domain, disrupting junctional complex formation.
Gain of Function (GOF)
Not reported for JPH4.
Dominant Negative (DN)
Missense variants (e.g., p.Gly153Arg) may interfere with wild-type junctophilin 4 assembly, impairing calcium channel clustering.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Excitation-contraction coupling (R-HSA-5576891)
• Calcium signaling pathway (KEGG: hsa04020)
• Cardiac muscle contraction (KEGG: hsa04260)
Protein Summary
Junctophilin 4 is a 628-amino acid protein containing a C-terminal transmembrane domain and multiple N-terminal MORN (membrane occupation and recognition nexus) repeats. It localizes to junctional membrane complexes where it bridges the plasma membrane and endoplasmic/sarcoplasmic reticulum, facilitating the close apposition required for efficient calcium-induced calcium release. In neurons, JPH4 is essential for dendritic spine formation and synaptic plasticity. In cardiac muscle, it contributes to the organization of dyadic junctions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| JPH4 Knockout HEK293 Cell Line | EDJ-KQ10101 | Human | 84502 | Details Get a Quote |
| JPH4 Knockout HeLa Cell Line | EDJ-KQ57603 | Human | 84502 | Details Get a Quote |
| JPH4 Knockout A-549 Cell Line | EDJ-KQ66100 | Human | 84502 | Details Get a Quote |
| JPH4 Knockout HCT 116 Cell Line | EDJ-KQ74520 | Human | 84502 | Details Get a Quote |
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