CLDN23

Chr 8

claudin 23

Also known as: CLDNL, hCG1646163

NCBI Gene: 137075 ENSG00000253958 UniProt: Q96B33 OMIM: 609203

The protein is an integral membrane component of tight junctions that provides calcium-independent cell adhesion and helps maintain the physical barrier between epithelial cell sheets. Mutations cause autosomal recessive deafness-118 (DFNB118), a form of nonsyndromic hearing loss. The gene shows low constraint against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in the associated hearing disorder.

OMIM ResearchSummary from RefSeq, UniProt

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 gene is expressed in germinal center B-cells, placenta and stomach as well as in colon tumor. This gene is down-regulated in intestinal type gastric cancer. [provided by RefSeq, Aug 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.75

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.75LOEUF

pLI 0.000

Z-score 0.00

OE 1.00 (0.56–1.75)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.81Z-score

OE missense 1.17 (1.05–1.31)

208 obs / 177.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.00 (0.56–1.75)

0≤0.351.4

Missense OE?1.17 (1.05–1.31)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 7 / 7.0Missense obs/exp: 208 / 177.5Syn Z: -1.89

Background carrier burden — how many people carry a rare variant somewhere in CLDN23?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

636 rare PASS variants

Rare truncating (LoF)

1 in 2,100

76 rare PASS variants

Rare synonymous (reference)

1 in 110

309 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLDN23. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 3,000
South Asian	~43k	1 in 120	1 in 630
Remaining (unassigned)	~30k	1 in 69	1 in 1,900
European (Finnish)	~26k	1 in 260	≈ 1 in 5,900
Admixed American	~22k	1 in 96	1 in 2,200
African / African American	~21k	1 in 61	1 in 730
East Asian	~20k	1 in 75	1 in 3,700
Ashkenazi Jewish	~13k	1 in 360	none seen
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓