The protein is an integral membrane component of tight junctions that creates physical barriers to prevent solutes and water from passing between epithelial cell sheets through calcium-independent cell-adhesion activity. Mutations cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis, a renal tubulopathy affecting magnesium and calcium handling. This condition follows autosomal recessive inheritance and the gene shows low constraint to loss-of-function variation.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.90
Clinical SummaryCLDN20
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

Tolerant — LoF & missense variants common in population
LoF Constraint
1.90LOEUF
pLI 0.005
Z-score -0.25
OE 1.17 (0.481.90)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.15Z-score
OE missense 1.04 (0.901.20)
126 obs / 121.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.17 (0.481.90)
00.351.4
Missense OE1.04 (0.901.20)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 3 / 2.6Missense obs/exp: 126 / 121.3Syn Z: 0.78
DN
0.6937th %ile
GOF
0.77top 25%
LOF
0.2776th %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

CLDN20 · 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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