IL33

Chr 9

interleukin 33

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

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…
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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ClinVar Variants
42 VUS of 59 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?1.15 (0.741.75)
00.351.4
Missense OE?1.25 (1.101.42)
00.61.4
Synonymous OE?1.14
01.21.6
LoF obs/exp: 13 / 11.3Missense obs/exp: 168 / 134.3Syn Z: -0.75

This gene — mechanism propensity

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

59 submitted variants in ClinVar

Classification Summary

VUS42
Likely Benign3
Benign6
42
VUS
3
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
42
0
0
42
Likely Benign
0
3
0
0
3
Benign
0
3
1
2
6
Total0481251

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

View in ClinVar →

156 pathogenic / likely-pathogenic (of 163) ClinVar copy-number / structural variants overlap IL33 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

IL33 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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
Healthy

Pulmonary Immune Cell-microbiome Interactions in the Healthy Lung

RECRUITING
NCT05846620Hvidovre University HospitalStarted 2023-04-17
Bronchoalveolar lavage
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
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
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
Obesity-associated Asthma

Metformin Treatment for Children With Obesity-associated Asthma

NOT YET RECRUITING
NCT07622290Phase PHASE3Prof Ibrahim JanahiStarted 2026-06
MetfominPlacebo
Post-Acute COVID-19 Syndrome

A Study of Apabetalone in Subjects With Long -COVID

RECRUITING
NCT06590324Phase PHASE2, PHASE3Resverlogix CorpStarted 2025-04-15
Apabetalone
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
InflamationCOPDOxidative Stress

Inflammation and Oxidative Stress in COPD

ENROLLING BY INVITATION
NCT07376161Esra YazarStarted 2026-01-06
Pulmonary Rehabilitation
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
Chronic Obstructive Pulmonary Disease Exacerbation

The CATALINA Study

RECRUITING
NCT05008081Wim JanssensStarted 2022-10-25
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