CLDN11

Chr 3AD

claudin 11

Also known as: HLD22, OSP, OTM

NCBI Gene: 5010 ENSG00000013297 UniProt: O75508 OMIM: 601326

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

ADLOEUF 0.391 OMIM phenotype

Clinical Summary— CLDN11

🧬

Gene-Disease Validity (ClinGen)

leukodystrophy, hypomyelinating, 22 · ADModerate

Moderate evidence — consider for supplementary testing

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 13 VUS of 23 total submissions

Explore recent and relevant literature in Research Assistant →

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

ClinVar Variant Classifications

23 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS13

Likely Benign4

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	2	0	0	2
Likely Pathogenic	0	0	0	0
VUS	0	13	0	13
Likely Benign	0	0	4	4
Benign	0	0	1	1
Total	2	13	5	20

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

22 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap CLDN11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →