CLDN34

Chr X

claudin 34

NCBI Gene: 100288814 ENSG00000234469 UniProt: H7C241

The protein functions in tight junction formation by mediating calcium-independent cell adhesion and obliterating intercellular spaces between cells. The gene is not highly constrained against loss-of-function variation, and no established human diseases have been definitively linked to CLDN34 mutations in the current literature.

ResearchSummary from RefSeq, UniProt

Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.74

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.74LOEUF

pLI 0.000

Z-score 0.01

OE 1.00 (0.56–1.74)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.43Z-score

OE missense 0.58 (0.46–0.73)

53 obs / 91.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.00 (0.56–1.74)

0≤0.351.4

Missense OE?0.58 (0.46–0.73)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 7 / 7.0Missense obs/exp: 53 / 91.4Syn Z: 0.02

Background carrier burden — how many people carry a rare variant somewhere in CLDN34?

gnomAD v4 · ~695k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 340

178 rare PASS variants

Rare truncating (LoF)

1 in 3,600

24 rare PASS variants

Rare synonymous (reference)

1 in 840

77 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLDN34. 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)	~546k	1 in 240	1 in 3,900
South Asian	~33k	1 in 1,100	≈ 1 in 8,300
Remaining (unassigned)	~30k	1 in 300	1 in 5,900
African / African American	~21k	1 in 390	1 in 3,800
Admixed American	~19k	1 in 530	1 in 3,100
East Asian	~18k	1 in 310	1 in 1,100
European (Finnish)	~17k	≈ 1 in 4,300	none seen
Ashkenazi Jewish	~12k	≈ 1 in 2,500	≈ 1 in 12,000
Middle Eastern	~2,726	≈ 1 in 550	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.

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