CLDN3

Chr 7

claudin 3

Also known as: C7orf1, CPE-R2, CPETR2, HRVP1, RVP1

NCBI Gene: 1365ENSG00000165215UniProt: O15551

Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this intronless gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is also a low-affinity receptor for Clostridium perfringens enterotoxin, and shares aa sequence similarity with a putative apoptosis-related protein found in rat. [provided by RefSeq, Jul 2008]

202
ClinVar variants
163
Pathogenic / LP
0.52
pLI score
2
Active trials
Clinical Summary— CLDN3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.52) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
163 Pathogenic / Likely Pathogenic· 39 VUS of 202 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.76LOEUF
pLI 0.522
Z-score 1.95
OE 0.16 (0.06–0.76)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.33Z-score
OE missense 0.70 (0.59–0.82)
106 obs / 152.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.16 (0.06–0.76)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.59–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.84
0≤1.21.6
LoF obs/exp: 1 / 6.3Missense obs/exp: 106 / 152.0Syn Z: 1.15

ClinVar Variant Classifications

202 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic157
Likely Pathogenic6
VUS39
157
Pathogenic
6
Likely Pathogenic
39
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
157
0
157
Likely Pathogenic
0
0
6
0
6
VUS
0
33
6
0
39
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0331690202

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

View in ClinVar →

Protein Context — Lollipop Plot

CLDN3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
CLAUDIN 3; CLDN3
MIM #602910 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Claudins and hepatocellular carcinoma.
Wang W et al.·Biomed Pharmacother
2024Review
ASCL2 contributes to clinical assessments of breast cancer and mediates tumor progression via the interaction with CLDN3.
Yin Y et al.·Sci Rep
2025
Elevated expression of HSF1 promotes the progression of colorectal cancer by activating CLDN3 transcription.
Shao Y et al.·Neoplasma
2025
Potential roles of claudin-3 and claudin-4 in ovarian cancer management.
Uthayanan L et al.·J Egypt Natl Canc Inst
2022Review
CLDN3 inhibits cancer aggressiveness via Wnt-EMT signaling and is a potential prognostic biomarker for hepatocellular carcinoma.
Jiang L et al.·Oncotarget
2014
p38 MAPK-mediated upregulation of claudin-3 and claudin-4 by gemcitabine contributes to chemoresistance in ovarian cancer.
Zhao J et al.·Int J Biochem Cell Biol
2025
Claudin-3 Loss of Expression Is a Prognostic Marker in Castration-Resistant Prostate Cancer.
Orea MJ et al.·Int J Mol Sci
2023
Claudins proteins in brain tumors: expression patterns and therapeutic target.
Romanowicz A et al.·Biochem Med (Zagreb)
2026Review
Toward Precision Medicine: Molecular Biomarkers of Response to Tofacitinib in Inflammatory Bowel Disease.
Bizjak A et al.·Genes (Basel)
2025Review
Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value.
Hong S et al.·J Ovarian Res
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Congenital Heart Disease (CHD)

Butyric Acid Supplementation for Gut Improvement After Cardiac Surgery in Kids

NOT YET RECRUITING
NCT06882772Phase PHASE1, PHASE2University of NebraskaStarted 2026-03
2 mL SunButyrate-TGPlacebo4 mL SunButyrate-TG
Sports NutritionBiochemical MarkersExercise Performance

Effect of a Short-term Multi-strain Probiotic Supplementation in Endurance Athletes

RECRUITING
NCT07252778Phase PHASE2, PHASE3Krzysztof Durkalec-MichalskiStarted 2025-11-20
MPRO supplementationPlacebo treatment

External Resources

Links to major genomics databases and tools