CLDN9

Chr 16AR

claudin 9

Also known as: DFNB116

NCBI Gene: 9080ENSG00000213937UniProt: O95484

This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. This protein is one of the entry cofactors for hepatitis C virus. Mouse studies revealed that this gene is required for the preservation of sensory cells in the hearing organ and the gene deficiency is associated with deafness. [provided by RefSeq, Jun 2010]

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 116MIM #619093
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CLDN9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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.
1.90LOEUF
pLI 0.000
Z-score -0.65
OE 1.30 (0.71–1.90)
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.
-1.08Z-score
OE missense 1.26 (1.11–1.42)
179 obs / 142.6 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.1.30 (0.71–1.90)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.26 (1.11–1.42)
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.1.36
0≤1.21.6
LoF obs/exp: 7 / 5.4Missense obs/exp: 179 / 142.6Syn Z: -2.42

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CLDN9 · 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 9; CLDN9
MIM #615799 · *

Deafness, autosomal recessive 116

MIM #619093

Molecular basis of disorder known

Autosomal recessive
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
Variants of human CLDN9 cause mild to profound hearing loss.
Ramzan M et al.·Hum Mutat
2021
A truncating CLDN9 variant is associated with autosomal recessive nonsyndromic hearing loss.
Sineni CJ et al.·Hum Genet
2019
Claudin-9 enhances the metastatic potential of hepatocytes via Tyk2/Stat3 signaling.
Liu H et al.·Turk J Gastroenterol
2019
The correlation among Claudin-9, Tyrosine kinase-2, and Signal transducers and activators of transcription-3 expressions in non-functioning pituitary adenoma and invasiveness.
Yasen A et al.·Neuro Endocrinol Lett
2023
Overexpression of the cell adhesion molecule claudin-9 is associated with invasion in pituitary oncocytomas.
Hong L et al.·Hum Pathol
2014
Molecular characterization and biomarker discovery in gastric cancer progression through transcriptome meta-analysis.
Matos TL et al.·Comput Biol Med
2024Meta-analysis
Therapeutic Potential of CLDN Family Proteins in Ovarian Cancer: Emerging Biomarkers and Targets.
Wu Y et al.·Front Biosci (Landmark Ed)
2025
A glycolysis-related gene signature predicts prognosis of patients with esophageal adenocarcinoma.
Kang H et al.·Aging (Albany NY)
2020Cohort
Humanisation of a claudin-1-specific monoclonal antibody for clinical prevention and cure of HCV infection without escape.
Colpitts CC et al.·Gut
2018
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

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools