CLDN9

Chr 16

claudin 9

This gene encodes claudin-9, an integral membrane protein that forms tight junctions and creates calcium-independent cell adhesion to prevent solutes and water from passing between epithelial cell sheets. Mutations cause autosomal recessive deafness (ARHL 116), specifically affecting sensory cells in the hearing organ. The gene shows low constraint to loss-of-function variation, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismLOEUF 1.90
Clinical SummaryCLDN9
🧬
Gene-Disease Validity (ClinGen)
hearing loss, autosomal recessive 116 · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.90LOEUF
pLI 0.000
Z-score -0.65
OE 1.30 (0.711.90)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.08Z-score
OE missense 1.26 (1.111.42)
179 obs / 142.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.30 (0.711.90)
00.351.4
Missense OE1.26 (1.111.42)
00.61.4
Synonymous OE1.36
01.21.6
LoF obs/exp: 7 / 5.4Missense obs/exp: 179 / 142.6Syn Z: -2.42
DN
0.78top 25%
GOF
0.86top 5%
LOF
0.1993th %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

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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