CLDN7

Chr 17

claudin 7

Also known as: CEPTRL2, CLDN-7, CPETRL2, Hs.84359, claudin-1

NCBI Gene: 1366 ENSG00000181885 UniProt: O95471 OMIM: 609131

The protein is an integral membrane component of tight junctions that creates physical barriers preventing solutes and water from passing through intercellular spaces between epithelial cells. Mutations in this gene cause autosomal recessive disorders including severe early-onset inflammatory bowel disease and genitourinary malformations. The gene shows tolerance to loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected patients.

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. Differential expression of this gene has been observed in different types of malignancies, including breast cancer, ovarian cancer, hepatocellular carcinomas, urinary tumors, prostate cancer, lung cancer, head and neck cancers, thyroid carcinomas, etc.. Alternatively spliced transcript variants encoding different isoforms have been found.[provided by RefSeq, May 2010]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.24

Clinical Summary— CLDN7

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.24LOEUF

pLI 0.003

Z-score 1.11

OE 0.59 (0.31–1.24)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.47Z-score

OE missense 0.88 (0.76–1.03)

111 obs / 125.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.31–1.24)

0≤0.351.4

Missense OE?0.88 (0.76–1.03)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 5 / 8.5Missense obs/exp: 111 / 125.9Syn Z: -0.37

This gene — mechanism propensity

0.79top 25%

GOF

0.73top 25%

LOF

0.2288th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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.