CLDN4

Chr 7

claudin 4

Also known as: CPE-R, CPER, CPETR, CPETR1, WBSCR8, hCPE-R

NCBI Gene: 1364ENSG00000189143UniProt: O14493

The protein encoded by this intronless gene belongs to the claudin family. Claudins are integral membrane proteins that are components of the epithelial cell tight junctions, which regulate movement of solutes and ions through the paracellular space. This protein is a high-affinity receptor for Clostridium perfringens enterotoxin (CPE) and may play a role in internal organ development and function during pre- and postnatal life. This gene is deleted in Williams-Beuren syndrome, a neurodevelopmental disorder affecting multiple systems. [provided by RefSeq, Sep 2013]

0
Active trials
164
Pathogenic / LP
196
ClinVar variants
41
Pubs (1 yr)
0.8
Missense Z
1.83
LOEUF
Clinical Summary— CLDN4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
164 Pathogenic / Likely Pathogenic· 30 VUS of 196 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.83LOEUF
pLI 0.000
Z-score -0.17
OE 1.08 (0.58–1.83)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.76Z-score
OE missense 0.83 (0.71–0.96)
124 obs / 150.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.08 (0.58–1.83)
0≤0.351.4
Missense OE0.83 (0.71–0.96)
0≤0.61.4
Synonymous OE1.14
0≤1.21.6
LoF obs/exp: 6 / 5.6Missense obs/exp: 124 / 150.2Syn Z: -0.93
GOFDN
DN
0.78top 25%
GOF
0.79top 25%
LOF
0.2582th %ile

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.

GOFprediction above median
DNprediction above median

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

196 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic158
Likely Pathogenic6
VUS30
Likely Benign2
158
Pathogenic
6
Likely Pathogenic
30
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
158
0
158
Likely Pathogenic
0
0
6
0
6
VUS
0
25
5
0
30
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total0261691196

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

CLDN4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients