CLDN5
Chr 22claudin 5
Also known as: AWAL, BEC1, CPETRL1, TMDVCF, TMVCF
This gene encodes claudin-5, an integral membrane protein that forms tight junction strands and plays a major role in obliterating the intercellular space to prevent solutes and water from passing freely between endothelial cell sheets. Mutations cause velocardiofacial syndrome, which follows an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function variants (pLI 0.90, LOEUF 0.41), indicating that complete loss of protein function is likely not tolerated.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is gain-of-function.
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CLDN5 · 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
Precision Medicine in the Treatment of Epilepsy
RECRUITINGDeciphering the Effect of Moderate Wine Consumption on Healthy Aging Through Postprandial Extracellular Vesicles.
RECRUITINGExternal Resources
Links to major genomics databases and tools