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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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JPH1
junctophilin 1
Chromosome 8 Β· 8q21.11
NCBI Gene: 56704Ensembl: ENSG00000104369.6HGNC: HGNC:14201UniProt: Q86VR1
78PubMed Papers
21Diseases
0Drugs
4Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingnucleoplasmsarcoplasmic reticulumendoplasmic reticulum membranecongenital myopathy 25type 2 diabetes mellituscongenital myopathyAbnormality of the skeletal system
✦AI Summary

JPH1 (junctophilin 1) is a structural protein essential for forming junctional membrane complexes that link the plasma membrane to the sarcoplasmic reticulum in skeletal muscle 1. JPH1 anchors to the sarcoplasmic reticulum via its C-terminal transmembrane domain while binding the transverse tubule membrane through N-terminal lipid-binding MORN motifs, thereby tethering these membranes to form triads 2. This organization supports voltage-induced calcium release and excitation-contraction coupling 3. Mechanistically, JPH1 forms homo- and heterodimeric interactions with JPH2, which stabilizes its recruitment at triads 2. JPH1 participates in store-operated calcium entry (SOCE) regulation and colocalizes with STIM1 at ER-plasma membrane contact sites 4. JPH1 associates with Huntingtin protein to modulate calcium fluxes 5. Disease relevance includes congenital myopathy 25 and genetic modification of Charcot-Marie-Tooth disease severity; JPH1 mutations impair SOCE rescue in GDAP1-related CMT2K 4. Reduced JPH1 protein levels cause skeletal myopathy and muscle weakness 1. Additionally, JPH1 expression correlates with liver metastasis risk in colorectal and breast cancers 6.

Sources cited
1
JPH1 structural organization and role in membrane tethering; loss of JPH1 causes skeletal myopathy
PMID: 35001666
2
JPH1 transmembrane domain and MORN motif functions; homo- and heterodimeric interactions with JPH2 at triads
PMID: 31315980
3
JPH1 supports voltage-induced calcium release in skeletal muscle
PMID: 35089322
4
JPH1 mutations impair store-operated calcium entry; JPH1 modifier role in GDAP1-related CMT2K disease
PMID: 25168384
5
JPH1 association with Huntingtin protein; role in excitation-contraction coupling and calcium fluxes
PMID: 36409218
6
JPH1 expression correlation with liver metastasis risk in colorectal and breast cancer
PMID: 31748560
Disease Associationsβ“˜21
congenital myopathy 25Open Targets
0.59Moderate
type 2 diabetes mellitusOpen Targets
0.47Moderate
congenital myopathyOpen Targets
0.46Moderate
Abnormality of the skeletal systemOpen Targets
0.38Weak
COVID-19Open Targets
0.30Weak
Barrett's esophagusOpen Targets
0.29Weak
phobic disorderOpen Targets
0.28Weak
lower urinary tract calculusOpen Targets
0.28Weak
Charcot-Marie-Tooth diseaseOpen Targets
0.15Weak
Charcot-Marie-Tooth disease axonal type 2KOpen Targets
0.15Weak
joint diseaseOpen Targets
0.11Weak
femoral neck fractureOpen Targets
0.11Weak
external ear diseaseOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
melanomaOpen Targets
0.05Suggestive
endometriosisOpen Targets
0.05Suggestive
Distal myopathy, Nonaka typeOpen Targets
0.05Suggestive
Autosomal dominant limb-girdle muscular dystrophy type 1DOpen Targets
0.05Suggestive
endometriosis of pelvic peritoneumOpen Targets
0.05Suggestive
myopathy, distal, 5Open Targets
0.05Suggestive
Congenital myopathy 25UniProt
Pathogenic Variants4
NM_020647.4(JPH1):c.1510del (p.Glu504fs)Pathogenic
Congenital myopathy|Congenital myopathy 25
β˜…β˜†β˜†β˜†2024β†’ Residue 504
NM_020647.4(JPH1):c.373del (p.Asp125fs)Likely pathogenic
Congenital myopathy|Congenital myopathy 25
β˜…β˜†β˜†β˜†2023β†’ Residue 125
NM_020647.4(JPH1):c.354C>A (p.Tyr118Ter)Likely pathogenic
Congenital myopathy|Congenital myopathy 25
β˜…β˜†β˜†β˜†2023β†’ Residue 118
NM_020647.4(JPH1):c.1738del (p.Leu580fs)Likely pathogenic
Congenital myopathy|Congenital myopathy 25
β˜…β˜†β˜†β˜†2023β†’ Residue 580
View on ClinVar β†—
Related Genes
ASPHProtein interaction94%CASQ1Protein interaction94%RYR1Protein interaction94%TRDNProtein interaction94%SYPL2Protein interaction79%CACNA1SProtein interaction77%
Tissue Expression6 tissues
Heart
100%
Brain
48%
Lung
22%
Liver
2%
Ovary
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
JPH1ASPHCASQ1RYR1TRDNSYPL2CACNA1S
PROTEIN STRUCTURE
Preparing viewer…
PDB7RW4 Β· 1.31 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.36Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.22 [0.14–0.36]
RankingsWhere JPH1 stands among ~20K protein-coding genes
  • #6,082of 20,598
    Most Researched78
  • #3,765of 5,498
    Most Pathogenic Variants4
  • #1,662of 17,882
    Most Constrained (LOEUF)0.36 Β· top 10%
Genes detectedJPH1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Junctophilin-1 is a modifier gene of GDAP1-related Charcot-Marie-Tooth disease.
PMID: 25168384
Hum Mol Genet Β· 2015
1.00
2
Molecular determinants of homo- and heteromeric interactions of Junctophilin-1 at triads in adult skeletal muscle fibers.
PMID: 31315980
Proc Natl Acad Sci U S A Β· 2019
0.90
3
Huntingtin regulates calcium fluxes in skeletal muscle.
PMID: 36409218
J Gen Physiol Β· 2023
0.80
4
Proteins of the Triadic Excitation-Contraction Coupling Complex in Skeletal Muscle.
PMID: 40097154
Cold Spring Harb Perspect Biol Β· 2025
0.70
5
Junctophilins 1, 2, and 3 all support voltage-induced Ca2+ release despite considerable divergence.
PMID: 35089322
J Gen Physiol Β· 2022
0.60