CLDN24

Chr 4

claudin 24

Also known as: CLDN21

NCBI Gene: 100132463 ENSG00000185758 UniProt: A6NM45 OMIM: 621614

The protein encoded by this gene is an integral membrane component of tight junctions that functions to prevent solutes and water from passing through the paracellular space between epithelial cell sheets and maintains cell polarity. The gene shows low constraint against loss-of-function variants (pLI near 0, LOEUF 1.85), suggesting that heterozygous loss-of-function mutations may be tolerated. Currently, no well-established human disease phenotypes have been definitively linked to mutations in this gene.

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. The protein encoded by this gene is 75% identical to the mouse homolog. This gene is upstream of the CLDN22 gene, which overlaps the WWC2 gene on the opposite strand in the genome.[provided by RefSeq, Aug 2010]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.85

Clinical Summary— CLDN24

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

26 VUS of 29 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.85LOEUF

pLI 0.000

Z-score -0.43

OE 1.18 (0.68–1.85)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.45Z-score

OE missense 0.88 (0.75–1.04)

98 obs / 111.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.18 (0.68–1.85)

0≤0.351.4

Missense OE?0.88 (0.75–1.04)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 8 / 6.8Missense obs/exp: 98 / 111.4Syn Z: -0.40

This gene — mechanism propensity

0.6259th %ile

GOF

0.80top 10%

LOF

0.2680th %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

29 submitted variants in ClinVar

ClinVar

Classification Summary

VUS26

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	26	26
Likely Benign	3	3
Benign	0	0
Total	29	29

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

View in ClinVar →

102 pathogenic / likely-pathogenic (of 109) ClinVar copy-number / structural variants overlap CLDN24 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →