CLDN4
Chr 7claudin 4
Also known as: CPE-R, CPER, CPETR, CPETR1, WBSCR8, hCPE-R
Claudin-4 is an integral membrane protein that regulates epithelial tight junction barrier properties and paracellular ion transport, particularly chloride permeability in renal collecting ducts. CLDN4 is deleted in Williams-Beuren syndrome, a multisystem neurodevelopmental disorder. The gene shows low constraint to loss-of-function variation (LOEUF 1.827), suggesting that complete loss may be tolerated when occurring as part of larger deletions.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
CLDN4 · 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