CLDN3

Chr 7

claudin 3

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

NCBI Gene: 1365ENSG00000165215UniProt: O15551OMIM: 602910

The protein is a barrier-forming claudin that plays a major role in tight junction formation by obliterating intercellular space through calcium-independent cell adhesion activity. Mutations cause autosomal recessive intellectual disability and hypocalciuric hypercalcemia, affecting neurological development and calcium homeostasis. The gene shows moderate constraint against loss-of-function variants, suggesting some intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.76
Clinical Summary— CLDN3
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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.52) — some intolerance to loss-of-function variants.
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ClinVar Variants
165 unique Pathogenic / Likely Pathogenic· 40 VUS of 205 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
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
1.33Z-score
OE missense 0.70 (0.59–0.82)
106 obs / 152.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.16 (0.06–0.76)
0≤0.351.4
Missense OE0.70 (0.59–0.82)
0≤0.61.4
Synonymous OE0.84
0≤1.21.6
LoF obs/exp: 1 / 6.3Missense obs/exp: 106 / 152.0Syn Z: 1.15
DN
0.74top 25%
GOF
0.78top 25%
LOF
0.2971th %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

205 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic159
Likely Pathogenic6
VUS40
159
Pathogenic
6
Likely Pathogenic
40
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
159
0
159
Likely Pathogenic
0
0
6
0
6
VUS
0
34
6
0
40
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0341710205

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
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