CLDN1

Chr 3

claudin 1

Also known as: CLD1, ILVASC, SEMP1

NCBI Gene: 9076 ENSG00000163347 UniProt: O95832

Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. Loss of function mutations result in neonatal ichthyosis-sclerosing cholangitis syndrome. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIchthyosis-sclerosing cholangitis neonatal syndrome

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

192

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.18

LOEUF

LOF

Mechanism· G2P

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?

1.18LOEUF

pLI 0.001

Z-score 1.19

OE 0.60 (0.33–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.03Z-score

OE missense 0.99 (0.85–1.15)

121 obs / 122.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.33–1.18)

0≤0.351.4

Missense OE?0.99 (0.85–1.15)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 6 / 10.1Missense obs/exp: 121 / 122.0Syn Z: -0.13

Background carrier burden — how many people carry a rare variant somewhere in CLDN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

275 rare PASS variants

Rare truncating (LoF)

1 in 5,300

30 rare PASS variants

Rare synonymous (reference)

1 in 490

103 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLDN1. 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 280	1 in 9,300
South Asian	~43k	1 in 260	1 in 1,700
Remaining (unassigned)	~30k	1 in 230	≈ 1 in 30,000
European (Finnish)	~27k	1 in 950	none seen
Admixed American	~22k	1 in 210	1 in 2,300
African / African American	~21k	1 in 280	≈ 1 in 6,900
East Asian	~20k	1 in 300	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 540	none seen
Middle Eastern	~2,884	1 in 170	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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓