IL33

Chr 9

interleukin 33

Also known as: C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV

NCBI Gene: 90865 ENSG00000137033 UniProt: O95760

IL33 encodes a cytokine that binds to the IL1RL1/ST2 receptor and activates NF-kappa-B and MAPK signaling pathways, playing essential roles in Th2 cell maturation and activation of mast cells, basophils, eosinophils, and natural killer cells. The gene shows extremely low constraint against loss-of-function variants (pLI near zero), suggesting it tolerates heterozygous inactivating mutations well. No definitive Mendelian diseases have been established for IL33 mutations in current medical literature.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a cytokine that binds to the IL1RL1/ST2 receptor. The encoded protein is involved in the maturation of Th2 cells and the activation of mast cells, basophils, eosinophils and natural killer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ResearchGenerating clinical summary…

Active trials

162

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.75

LOEUF

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?

1.75LOEUF

pLI 0.000

Z-score -0.45

OE 1.15 (0.74–1.75)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.03Z-score

OE missense 1.25 (1.10–1.42)

168 obs / 134.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.15 (0.74–1.75)

0≤0.351.4

Missense OE?1.25 (1.10–1.42)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 13 / 11.3Missense obs/exp: 168 / 134.3Syn Z: -0.75

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

IL33 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Immune ThrombocytopeniaSystem; Lupus Erythematosus

The Value of Interleukin-1β and Interleukin-33 Genetic Expression in the Pathogenesis and Differentiation of Primary ITP and SLE-Related Thrombocytopenia

NOT YET RECRUITING

NCT07298733Sohag UniversityStarted 2026-01-01

measuring gene expression

Ulcerative Colitis

Multi-Strain Probiotics Supplementation With Standard Care in Mild to Moderate Ulcerative Colitis

RECRUITING

NCT06595719Phase NANational University of MalaysiaStarted 2024-02-23

Multi-Strain ProbioticsPlacebo

Chronic Obstructive Pulmonary Disease Exacerbation

The CATALINA Study

RECRUITING

NCT05008081Wim JanssensStarted 2022-10-25