IL33 Gene

HGNC Family	Interleukins (IL)
Name	interleukin 33
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n IL‐33, a member of the interleukin‐1 cytokine family, functions in a dual capacity as both a nuclear factor and an extracellular “alarmin.” It is constitutively expressed in endothelial and epithelial cells and, upon cellular stress or damage, is released into the extracellular milieu to rapidly alert and activate the immune system."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Engaging its receptor ST2, IL‐33 activates key signaling pathways including NF‐κB and MAP kinases, which drive the production of type 2 cytokines—most notably IL‐4, IL‐5, and IL‐13—from diverse immune cells such as Th2 lymphocytes, group 2 innate lymphoid cells (ILC2s) and mast cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n IL‐33’s bioactivity is governed by its mode of processing. Contrary to earlier assumptions that proteolytic cleavage by inflammatory caspases is necessary for activation, studies now show that full‐length IL‐33 is active and that caspase‐mediated proteolysis during apoptosis actually dampens its function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In contrast, enzymes derived from neutrophils can generate more potent mature forms of IL‐33, thereby intensifying its ability to promote inflammation.\n "}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functionally, IL‐33 is central to the amplification of type 2 immune responses in mucosal tissues. It induces rapid cytokine production that underlies allergic airway inflammation, goblet cell hyperplasia, and helminth expulsion, while also modulating regulatory T cell responses that are critical for tissue homeostasis. Beyond mucosal immunity, IL‐33 has been implicated in the pathogenesis of cardiovascular and joint inflammatory diseases, including rheumatoid arthritis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore IL‐33’s multifaceted role as an endogenous danger signal and amplifier of type 2 immunity. Its capacity to integrate cues from tissue damage and modulate both innate and adaptive immune responses makes IL‐33 a promising target for therapeutic intervention in a wide spectrum of allergic and inflammatory diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jochen Schmitz, Alexander Owyang, Elizabeth Oldham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2005.09.015"}], "href": "https://doi.org/10.1016/j.immuni.2005.09.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16286016"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16286016"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christine Moussion, Nathalie Ortega, Jean-Philippe Girard "}, {"type": "b", "children": [{"type": "t", "text": "The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0003331"}], "href": "https://doi.org/10.1371/journal.pone.0003331"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18836528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18836528"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "April E Price, Hong-Erh Liang, Brandon M Sullivan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Systemically dispersed innate IL-13-expressing cells in type 2 immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1003988107"}], "href": "https://doi.org/10.1073/pnas.1003988107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20534524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20534524"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Keisuke Oboki, Tatsukuni Ohno, Naoki Kajiwara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IL-33 is a crucial amplifier of innate rather than acquired immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1003059107"}], "href": "https://doi.org/10.1073/pnas.1003059107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20937871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20937871"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Corinne Cayrol, Jean-Philippe Girard "}, {"type": "b", "children": [{"type": "t", "text": "The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0812690106"}], "href": "https://doi.org/10.1073/pnas.0812690106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19439663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19439663"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hiroko Hayakawa, Morisada Hayakawa, Akihiro Kume, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M704916200"}], "href": "https://doi.org/10.1074/jbc.M704916200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17623648"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17623648"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Rahul Kakkar, Richard T Lee "}, {"type": "b", "children": [{"type": "t", "text": "The IL-33/ST2 pathway: therapeutic target and novel biomarker."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Drug Discov (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nrd2660"}], "href": "https://doi.org/10.1038/nrd2660"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18827826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18827826"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Damo Xu, Hui-Rong Jiang, Peter Kewin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IL-33 exacerbates antigen-induced arthritis by activating mast cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0801898105"}], "href": "https://doi.org/10.1073/pnas.0801898105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18667700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18667700"}]}]}]}
Synonyms	NF-HEV, IL1F11, DVS27, NFEHEV, C9ORF26
Proteins	IL33_HUMAN
NCBI Gene ID	90865
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

IL33 has 9,093 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 112 datasets.

Click the + buttons to view associations for IL33 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

IL33 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of IL33 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of IL33 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of IL33 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of IL33 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of IL33 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of IL33 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of IL33 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of IL33 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of IL33 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of IL33 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of IL33 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with IL33 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of IL33 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of IL33 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of IL33 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of IL33 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing IL33 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing IL33 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing IL33 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with IL33 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with IL33 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of IL33 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with IL33 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with IL33 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with IL33 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by IL33 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with IL33 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with IL33 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with IL33 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with IL33 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with IL33 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with IL33 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at IL33 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of IL33 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of IL33 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing IL33 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with IL33 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with IL33 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing IL33 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of IL33 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.