IL33

Chr 9

interleukin 33

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

NCBI Gene: 90865ENSG00000137033UniProt: O95760

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]

218
ClinVar variants
153
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical Summary— IL33
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
153 Pathogenic / Likely Pathogenic· 46 VUS of 218 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.03Z-score
OE missense 1.25 (1.10–1.42)
168 obs / 134.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.15 (0.74–1.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.25 (1.10–1.42)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 13 / 11.3Missense obs/exp: 168 / 134.3Syn Z: -0.75

ClinVar Variant Classifications

218 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic147
Likely Pathogenic6
VUS46
Likely Benign5
Benign6
147
Pathogenic
6
Likely Pathogenic
46
VUS
5
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
147
0
147
Likely Pathogenic
0
0
6
0
6
VUS
0
41
5
0
46
Likely Benign
0
3
2
0
5
Benign
0
3
1
2
6
Total0471612210

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
INTERLEUKIN 33; IL33
MIM #608678 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeting interleukin-33 and thymic stromal lymphopoietin pathways for novel pulmonary therapeutics in asthma and COPD.
Calderon AA et al.·Eur Respir Rev
2023Review
Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex.
Strickson S et al.·Eur Respir J
2023
Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis.
Bousquet J et al.·Allergy
2023Review
Sounding the alarmins-The role of alarmin cytokines in asthma.
Gauvreau GM et al.·Allergy
2023Review
Mapping human haematopoietic stem cells from haemogenic endothelium to birth.
Calvanese V et al.·Nature
2022
Towards precision medicine in COPD: Targeting type 2 cytokines and alarmins.
Varricchi G et al.·Eur J Intern Med
2024Review
Interleukin-33 (IL-33): A critical review of its biology and the mechanisms involved in its release as a potent extracellular cytokine.
Cayrol C et al.·Cytokine
2022Review
Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: A randomized clinical trial.
Kelsen SG et al.·J Allergy Clin Immunol
2021Clinical trial
Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation.
Hong H et al.·Allergy
2020Review
TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation.
Schmitt P et al.·J Exp Med
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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
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
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
Low Back Pain

The Prognostic Value of Biomarkers and the Effect of Tolperisone in Acute Low Back Pain and Sciatic Pain "BETA"

ACTIVE NOT RECRUITING
NCT05544656Phase PHASE3Semmelweis UniversityStarted 2019-12-13
Tolperisone HydrochloridePlacebo
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
ALS (Amyotrophic Lateral Sclerosis)FTDNeuropathic

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

NOT YET RECRUITING
NCT06856850Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaStarted 2025-06
Healthy

Pulmonary Immune Cell-microbiome Interactions in the Healthy Lung

RECRUITING
NCT05846620Hvidovre University HospitalStarted 2023-04-17
Bronchoalveolar lavage
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
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 Obstructive Pulmonary Disease Exacerbation

The CATALINA Study

RECRUITING
NCT05008081Wim JanssensStarted 2022-10-25
Post-Acute COVID-19 Syndrome

A Study of Apabetalone in Subjects With Long -COVID

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

Inflammation and Oxidative Stress in COPD

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

External Resources

Links to major genomics databases and tools