IL33

Chr 9

interleukin 33

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

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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.75
Clinical SummaryIL33
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
11 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.75LOEUF
pLI 0.000
Z-score -0.45
OE 1.15 (0.741.75)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.03Z-score
OE missense 1.25 (1.101.42)
168 obs / 134.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.15 (0.741.75)
00.351.4
Missense OE1.25 (1.101.42)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 13 / 11.3Missense obs/exp: 168 / 134.3Syn Z: -0.75
DN
0.7229th %ile
GOF
0.4974th %ile
LOF
0.3551th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Sleep DisorderAging

Evaluation of Urolithin A and Fisetin on Improving Sleep and Aging Biomarkers

RECRUITING
NCT06990256Phase NAHuazhong University of Science and TechnologyStarted 2025-09-16
Fisetin interventionPlaceboUrolithin A intervention
Chronic Airway InflammationAsthmaChronic Obstructive Pulmonary Disease

Respiratory Microbiota, Infection Characteristics and Imaging Manifestations in Patients With Chronic Airway Inflammation

NOT YET RECRUITING
NCT06938022First Affiliated Hospital of Ningbo UniversityStarted 2025-04-15
InflamationCOPDOxidative Stress

Inflammation and Oxidative Stress in COPD

ENROLLING BY INVITATION
NCT07376161Esra YazarStarted 2026-01-06
Pulmonary Rehabilitation
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 COPD

A Study to Evaluate 9MW1911 in Patients With Chronic Obstructive Pulmonary Disease (COPD)

RECRUITING
NCT07292714Phase PHASE2Mabwell (Shanghai) Bioscience Co., Ltd.Started 2025-07-15
9MW1911Phase II placebo
Healthy

Pulmonary Immune Cell-microbiome Interactions in the Healthy Lung

RECRUITING
NCT05846620Hvidovre University HospitalStarted 2023-04-17
Bronchoalveolar lavage
Post-Acute COVID-19 Syndrome

A Study of Apabetalone in Subjects With Long -COVID

RECRUITING
NCT06590324Phase PHASE2, PHASE3Resverlogix CorpStarted 2025-04-15
Apabetalone
Migraine DisordersPainAutoimmune Diseases

The Role of Cytokines and Regulatory T Lymphocytes in Migraine Pathophysiology.

RECRUITING
NCT06426316Phase NAUniversity Hospital, Clermont-FerrandStarted 2025-06-02
Blood test
ALS (Amyotrophic Lateral Sclerosis)FTDNeuropathic

Disease Biosignatures in ALS/FTD Spectrum: New Impactful Biological Perspectives Beyond Clinical Approaches

RECRUITING
NCT06856850Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaStarted 2025-02-27
Chronic Obstructive Pulmonary Disease Exacerbation

The CATALINA Study

RECRUITING
NCT05008081Wim JanssensStarted 2022-10-25
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
Clinical Literature
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