CLDN18

Chr 3

claudin 18

Also known as: SFTA5, SFTPJ

NCBI Gene: 51208 ENSG00000066405 UniProt: P56856 OMIM: 609210

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. This gene is upregulated in patients with ulcerative colitis and highly overexpressed in infiltrating ductal adenocarcinomas. PKC/MAPK/AP-1 (protein kinase C/mitogen-activated protein kinase/activator protein-1) dependent pathway regulates the expression of this gene in gastric cells. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jun 2010]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.27

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — CLDN18

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.27LOEUF

pLI 0.000

Z-score 0.96

OE 0.68 (0.39–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.61Z-score

OE missense 0.86 (0.75–1.00)

135 obs / 156.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.39–1.27)

0≤0.351.4

Missense OE?0.86 (0.75–1.00)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 7 / 10.3Missense obs/exp: 135 / 156.4Syn Z: 0.41

Background carrier burden — how many people carry a rare variant somewhere in CLDN18?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

393 rare PASS variants

Rare truncating (LoF)

1 in 2,700

54 rare PASS variants

Rare synonymous (reference)

1 in 280

176 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLDN18. 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 3,400
South Asian	~43k	1 in 190	1 in 1,100
Remaining (unassigned)	~30k	1 in 160	1 in 4,300
European (Finnish)	~27k	1 in 480	1 in 680
Admixed American	~22k	1 in 290	1 in 310
African / African American	~21k	1 in 110	1 in 1,100
East Asian	~20k	1 in 210	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 460	none seen
Middle Eastern	~2,884	1 in 140	≈ 1 in 2,800

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 ↓