CLDN6

Chr 16

claudin 6

NCBI Gene: 9074ENSG00000184697UniProt: P56747

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. This gene encodes a component of tight junction strands, which is a member of the claudin family. The protein is an integral membrane protein and is one of the entry cofactors for hepatitis C virus. The gene methylation may be involved in esophageal tumorigenesis. This gene is adjacent to another family member CLDN9 on chromosome 16.[provided by RefSeq, Aug 2010]

85
ClinVar variants
35
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— CLDN6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 Pathogenic / Likely Pathogenic· 45 VUS of 85 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.58LOEUF
pLI 0.004
Z-score 0.60
OE 0.72 (0.35–1.58)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.43Z-score
OE missense 1.10 (0.96–1.26)
148 obs / 134.0 exp
Tolerant

Tolerant to missense variation

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.0.72 (0.35–1.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.10 (0.96–1.26)
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.1.35
0≤1.21.6
LoF obs/exp: 4 / 5.5Missense obs/exp: 148 / 134.0Syn Z: -2.18

ClinVar Variant Classifications

85 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
VUS45
Likely Benign4
Benign1
35
Pathogenic
45
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
0
0
0
VUS
0
36
9
0
45
Likely Benign
0
4
0
0
4
Benign
0
0
0
1
1
Total04044185

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

View in ClinVar →

Protein Context — Lollipop Plot

CLDN6 · 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 6; CLDN6
MIM #615798 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Preclinical efficacy and pharmacokinetics of an RNA-encoded T cell-engaging bispecific antibody targeting human claudin 6.
Stadler CR et al.·Sci Transl Med
2024
CLDN6 inhibits breast cancer growth and metastasis through SREBP1-mediated RAS palmitoylation.
Jin Q et al.·Cell Mol Biol Lett
2024
Claudin 1, 4, 6 and 18 isoform 2 as targets for the treatment of cancer (Review).
Katoh M et al.·Int J Mol Med
2024Review
SAIL66, a next generation CLDN6-targeting T-cell engager, demonstrates potent antitumor efficacy through dual binding to CD3/CD137.
Kamikawa T et al.·J Immunother Cancer
2024
Systematic characterization of antibody-drug conjugate targets in central nervous system tumors.
Coy S et al.·Neuro Oncol
2024
A mini-overview of antibody-drug conjugates in platinum-resistant ovarian cancer: A preclinical and clinical perspective.
Zhao Y et al.·Int J Biol Macromol
2025Review
Claudins and hepatocellular carcinoma.
Wang W et al.·Biomed Pharmacother
2024Review
CLDN6: From Traditional Barrier Function to Emerging Roles in Cancers.
Qu H et al.·Int J Mol Sci
2021Review
CLDN6 inhibits colorectal cancer proliferation dependent on restraining p53 ubiquitination via ZO-1/PTEN axis.
Dong Y et al.·Cell Signal
2023
The role of claudin-6 in chromophobe renal cell carcinoma.
Erlmeier F et al.·Histol Histopathol
2023
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
Solid Tumor

A Clinical Study of the Safety and Effectiveness of an Investigational Cell Therapy Given With and Without an Investigational RNA-based Vaccine in Patients With Organ Tumors

RECRUITING
NCT04503278Phase PHASE1BioNTech Cell & Gene Therapies GmbHStarted 2020-09-16
CLDN6 CAR-TCLDN6 uRNA-LPX/CLDN6 modRNA-LPX

External Resources

Links to major genomics databases and tools