TJP1
Chr 15tight junction protein 1
Also known as: ZO-1
TJP1 encodes a tight junction scaffolding protein that links transmembrane proteins to the actin cytoskeleton, regulating the movement of substances between epithelial and endothelial cells and maintaining cell polarity. Mutations cause autosomal dominant progressive familial intrahepatic cholestasis type 4, which presents in infancy with cholestasis, pruritus, and progressive liver disease. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0, LOEUF 0.071), indicating that haploinsufficiency is likely pathogenic.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
TJP1 · 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