JPH3
Chr 16ADjunctophilin 3
Also known as: CAGL237, HDL2, JP-3, JP3, TNRC22
The protein forms junctional membrane complexes that link the plasma membrane with the endoplasmic reticulum in brain neurons, providing structural foundation for cross-talk between cell surface and intracellular calcium release channels. CAG/CTG repeat expansions (40-59 repeats) in the 3' UTR cause Huntington disease-like 2 through a loss-of-function mechanism, inherited in an autosomal dominant pattern. The protein is brain-specific and functions in neurons involved in motor coordination and memory.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
JPH3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools