CLDN11

Chr 3

claudin 11

Also known as: HLD22, OSP, OTM

NCBI Gene: 5010 ENSG00000013297 UniProt: O75508

The protein encoded by this gene is claudin-11, a tight junction protein that serves as a major component of central nervous system myelin and regulates oligodendrocyte proliferation and migration. Mutations cause leukodystrophy, hypomyelinating, 22, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI = 0.91), consistent with its critical role in CNS myelination.

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 protein encoded by this gene is a major component of central nervous system (CNS) myelin and plays an important role in regulating proliferation and migration of oligodendrocytes. Mouse studies showed that the gene deficiency results in deafness and loss of the Sertoli cell epithelial phenotype in the testis. This protein is a tight junction protein at the human blood-testis barrier (BTB), and the BTB disruption is related to a dysfunction of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Aug 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeukodystrophy, hypomyelinating, 22

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · leukodystrophy, hypomyelinating, 22 · AD · ClinGen 2026

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

0.39

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.39LOEUF

pLI 0.911

Z-score 2.58

OE 0.00 (0.00–0.39)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.76Z-score

OE missense 0.56 (0.46–0.68)

72 obs / 128.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.39)

0≤0.351.4

Missense OE?0.56 (0.46–0.68)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 0 / 7.8Missense obs/exp: 72 / 128.1Syn Z: 0.88

Background carrier burden — how many people carry a rare variant somewhere in CLDN11?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 350

186 rare PASS variants

Rare truncating (LoF)

1 in 29,000

7 rare PASS variants

Rare synonymous (reference)

1 in 420

127 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLDN11. 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 470	1 in 29,000
South Asian	~43k	1 in 360	none seen
Remaining (unassigned)	~30k	1 in 460	none seen
European (Finnish)	~27k	1 in 810	≈ 1 in 13,000
Admixed American	~22k	1 in 650	≈ 1 in 7,600
African / African American	~21k	1 in 930	none seen
East Asian	~20k	1 in 520	none seen
Ashkenazi Jewish	~13k	1 in 1,000	≈ 1 in 13,000
Middle Eastern	~2,884	≈ 1 in 960	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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓