TJP2
Chr 9ARtight junction protein 2
Also known as: C9DUPq21.11, DFNA51, DUP9q21.11, FHCA1, PFIC4, X104, ZO2
The protein functions as a component of tight junction barriers in epithelial and endothelial cells and is necessary for proper tight junction assembly. Mutations cause progressive familial intrahepatic cholestasis type 4 and familial hypercholanemia, both involving hepatic bile acid metabolism abnormalities. This gene follows autosomal recessive inheritance and is highly constrained against loss-of-function variation (pLI near 0, LOEUF 0.635).
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TJP2 · 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
External Resources
Links to major genomics databases and tools