IL33: Interleukin 33 Gene - Function, Expression, and Disease Associations
Comprehensive biomedical overview of the IL33 gene, including genomic context, protein function, tissue expression, and clinical relevance.
Gene Information Card
| Symbol | IL33 |
|---|---|
| Full Name | Interleukin 33 |
| Gene Type | protein-coding |
| Chromosomal Location | 9p24.1 |
| NCBI Gene ID | 90865 ncbi.nlm.nih.gov/gene/90865 |
| Ensembl ID | ENSG00000137033 |
| UniProt ID | O95760 |
| OMIM ID | 608678 |
| HGNC ID | 16028 |
| Aliases | C9orf26, DVS27, IL-33, IL1F11, NF-HEV |
Description
IL33 (Interleukin 33) is a protein-coding gene that encodes a member of the IL-1 cytokine family. The protein is constitutively expressed in endothelial cells, epithelial cells, and fibroblast-like cells, and functions as both a cytokine and a nuclear factor. It binds to the ST2 receptor (IL1RL1) and activates NF-κB and MAPK signaling pathways, playing key roles in type 2 immune responses, allergic inflammation, and tissue homeostasis. IL33 is also involved in the regulation of gene expression in the nucleus via chromatin association.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Asthma | IL33 promotes Th2 cytokine production via ST2 signaling, driving airway inflammation and hyperresponsiveness. | GWAS and expression studies (NCBI, OMIM) |
| Atopic Dermatitis | Increased IL33 expression in keratinocytes triggers type 2 inflammation and pruritus. | Expression analysis (UniProt, OMIM) |
| Allergic Rhinitis | IL33 released from epithelial cells activates ILC2s and mast cells, exacerbating allergic responses. | Functional studies (NCBI) |
| Inflammatory Bowel Disease | IL33/ST2 signaling contributes to intestinal inflammation and fibrosis. | Association studies (OMIM) |
| Cardiovascular Disease | IL33 has protective roles in atherosclerosis via ST2 signaling, but also promotes fibrosis. | Experimental models (UniProt) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Skin | 8.3 | Medium |
| Small Intestine | 6.7 | Low |
| Stomach | 5.9 | Low |
| Spleen | 4.2 | Low |
| Heart | 3.8 | Low |
| Adipose Tissue | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 15.2 | High expression |
| HaCaT (keratinocyte) | 10.8 | Moderate expression |
| HUVEC (endothelial) | 8.5 | Moderate expression |
| HEK293 (embryonic kidney) | 2.3 | Low expression |
| THP-1 (monocyte) | 1.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3939286 | SNP (intronic) | 0.25 (G allele) | Associated with asthma risk (GWAS) |
| rs1342326 | SNP (intergenic) | 0.18 (A allele) | Associated with eosinophil counts |
| c.1A>G (p.Met1?) | Missense (start loss) | <0.01 | Likely loss of function, rare |
| c.337C>T (p.Arg113Trp) | Missense | <0.01 | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
Rare start-loss and missense variants predicted to reduce IL33 protein levels or disrupt secretion, potentially impairing type 2 immune responses.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported; overexpression in disease contexts is primarily transcriptional.
Dominant Negative (DN)
No dominant-negative mutations described for IL33.
View complete mutation data：
Gene Ontology (GO)
Pathways
• IL-33/ST2 signaling pathway (Reactome: R-HSA-449147)
• NF-κB signaling pathway (KEGG: hsa04064)
• MAPK signaling pathway (KEGG: hsa04010)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
Protein Summary
The IL33 protein (UniProt O95760) is a 270-amino acid cytokine with a nuclear localization signal and an IL-1-like domain. It is stored in the nucleus of endothelial and epithelial cells and released upon cellular damage or stress. Full-length IL33 (30 kDa) is cleaved by proteases (e.g., calpain, elastase) into mature forms (18-20 kDa) with enhanced receptor-binding activity. It signals through the ST2/IL1RAcP receptor complex, activating NF-κB and MAPK pathways. IL33 also acts as a chromatin-associated nuclear factor, regulating gene expression in a cell-type-specific manner.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL33 Knockout HEK293 Cell Line | EDJ-KQ1106 | Human | 90865 | Details Get a Quote |
| IL33 Knockout HeLa Cell Line | EDJ-KQ57787 | Human | 90865 | Details Get a Quote |
| IL33 Knockout A-549 Cell Line | EDJ-KQ66284 | Human | 90865 | Details Get a Quote |
| IL33 Knockout HCT 116 Cell Line | EDJ-KQ74702 | Human | 90865 | Details Get a Quote |
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