CLDN2

Chr XXLR

claudin 2

Also known as: OAZON, claudin-2

NCBI Gene: 9075 ENSG00000165376 UniProt: P57739 OMIM: 300520

This protein forms paracellular channels in tight junctions that are selective for cations and water, regulating sodium and water transport in the intestine, kidney proximal tubules, and hepatobiliary tract. Mutations cause azoospermia with obstructive features and nephrolithiasis in males. The gene follows X-linked recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene product belongs to the claudin protein family whose members have been identified as major integral membrane proteins localized exclusively at tight junctions. Claudins are expressed in an organ-specific manner and regulate tissue-specific physiologic properties of tight junctions. This protein is expressed in the intestine. Alternatively spliced transcript variants with different 5' untranslated region have been found for this gene.[provided by RefSeq, Jan 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Azoospermia, obstructive, with nephrolithiasisMIM #301060

XLR

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.75

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.75LOEUF

pLI 0.703

Z-score 1.85

OE 0.00 (0.00–0.75)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

1.61Z-score

OE missense 0.51 (0.40–0.66)

44 obs / 86.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.75)

0≤0.351.4

Missense OE?0.51 (0.40–0.66)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 0 / 4.0Missense obs/exp: 44 / 86.2Syn Z: 0.83

Background carrier burden — how many people carry a rare variant somewhere in CLDN2?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 600

120 rare PASS variants

Rare truncating (LoF)

1 in 240,000

3 rare PASS variants

Rare synonymous (reference)

1 in 1,100

79 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLDN2. 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)	~561k	1 in 800	≈ 1 in 280,000
South Asian	~36k	1 in 350	none seen
Remaining (unassigned)	~31k	1 in 540	≈ 1 in 31,000
European (Finnish)	~27k	1 in 3,100	none seen
Admixed American	~23k	1 in 660	none seen
African / African American	~21k	1 in 370	none seen
East Asian	~20k	1 in 1,300	none seen
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,758	1 in 390	none seen

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.