JPH1

Chr 8ADAR

junctophilin 1

Also known as: CMT2K, CMYO25, JP-1, JP1

NCBI Gene: 56704 ENSG00000104369 UniProt: Q9HDC5 OMIM: 605266

Junctophilin-1 forms junctional membrane complexes that link the plasma membrane with the sarcoplasmic reticulum in skeletal muscle, providing structural foundation for calcium release during muscle contraction. Mutations cause autosomal recessive congenital myopathy with characteristic histopathologic features including abnormal triad structure and calcium handling defects. This gene is highly constrained against loss-of-function variants, indicating critical importance for normal muscle function.

OMIM ResearchSummary from RefSeq, UniProt

Junctional complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum are a common feature of all excitable cell types and mediate cross talk between cell surface and intracellular ion channels. The protein encoded by this gene is a component of junctional complexes and is composed of a C-terminal hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining cytoplasmic domain that shows specific affinity for the plasma membrane. This gene is a member of the junctophilin gene family. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.412 OMIM phenotypes

Clinical Summary— JPH1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 75 VUS of 106 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.767

Z-score 3.60

OE 0.18 (0.09–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.46Z-score

OE missense 0.80 (0.73–0.88)

340 obs / 424.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.18 (0.09–0.41)

0≤0.351.4

Missense OE?0.80 (0.73–0.88)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 4 / 22.4Missense obs/exp: 340 / 424.9Syn Z: 0.87

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateJPH1-related congenital myopathy with ptosisLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.4388th %ile

GOF

0.5465th %ile

LOF

0.71top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

106 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic3

VUS75

Likely Benign8

Benign7

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	3	0	0	0	3
VUS	0	73	2	0	75
Likely Benign	0	1	1	6	8
Benign	0	4	0	3	7
Total	4	78	3	9	94

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

28 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap JPH1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →