CLDN10

Chr 13

claudin 10

Also known as: CPETRL3, HELIX, OSP-L, OSPL

NCBI Gene: 9071 ENSG00000134873 UniProt: P78369

The protein forms paracellular channels in tight junction strands that regulate epithelial permeability by creating selective pathways for ions to pass between cells. Mutations cause HELIX syndrome, an autosomal recessive disorder. The gene shows low constraint against loss-of-function variants (pLI 0.0008, LOEUF 1.22), consistent with the recessive inheritance pattern.

ResearchSummary from RefSeq, OMIM, 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 expression level of this gene is associated with recurrence of primary hepatocellular carcinoma. Six alternatively spliced transcript variants encoding different isoforms have been reported, but the transcript sequences of some variants are not determined.[provided by RefSeq, Jun 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHELIX syndrome

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.22

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.22LOEUF

pLI 0.001

Z-score 1.09

OE 0.62 (0.34–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.54Z-score

OE missense 0.87 (0.74–1.01)

114 obs / 131.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.34–1.22)

0≤0.351.4

Missense OE?0.87 (0.74–1.01)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 6 / 9.7Missense obs/exp: 114 / 131.3Syn Z: 0.71

Background carrier burden — how many people carry a rare variant somewhere in CLDN10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

362 rare PASS variants

Rare truncating (LoF)

1 in 2,900

67 rare PASS variants

Rare synonymous (reference)

1 in 130

164 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLDN10. 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)	~556k	1 in 270	1 in 4,500
South Asian	~43k	1 in 200	1 in 1,900
Remaining (unassigned)	~30k	1 in 190	1 in 3,000
European (Finnish)	~27k	1 in 1,200	1 in 2,900
Admixed American	~22k	1 in 270	1 in 3,300
African / African American	~21k	1 in 230	1 in 2,800
East Asian	~20k	1 in 140	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 540	1 in 2,600
Middle Eastern	~2,884	1 in 170	≈ 1 in 2,900

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓