IL21 Gene

HGNC Family Interleukins (IL)
Name interleukin 21
Description This gene encodes a member of the common-gamma chain family of cytokines with immunoregulatory activity. The encoded protein plays a role in both the innate and adaptive immune responses by inducing the differentiation, proliferation and activity of multiple target cells including macrophages, natural killer cells, B cells and cytotoxic T cells. Dysregulation of this gene plays a role in multiple immune-mediated diseases including lupus, psoriasis and chronic inflammatory diseases. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
Summary
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In the presence of costimulatory signals such as CD40 ligand, IL‑21 induces key transcription factors (e.g. BLIMP‑1) while also modulating factors like Bcl‑6, thereby guiding the transition from activated B cells to antibody‐secreting cells and sustaining long‐lived memory responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its B cell–directed actions, IL‑21 is deeply implicated in the differentiation and function of T cell subsets and in the genetic predisposition to autoimmune diseases. Along with transforming growth factor‑β, IL‑21 can drive the development of human T helper 17 cells, and it is instrumental in expanding T peripheral helper cells that support autoreactive B cell responses in disorders such as systemic lupus erythematosus and rheumatoid arthritis. Genetic studies have linked variations in the IL2/IL21 locus with conditions including alopecia areata, celiac disease, and inflammatory bowel disease, reinforcing its multifaceted role in autoimmunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIL‑21 also modulates innate immunity and is being exploited for immunotherapeutic applications. Studies using genetically engineered antigen‐presenting cells expressing membrane‐bound IL‑21 demonstrate its impressive capacity to expand natural killer (NK) cells with enhanced telomere lengths, while in cooperation with IL‑15 it promotes interferon‑γ production by NK and T cells. In the tumor microenvironment, IL‑21 has been shown to contribute to a pivotal Tfh/B cell axis favoring improved survival in colorectal cancer, and it enhances the generation of high‐affinity cytotoxic T lymphocytes in chronic viral infections. In other malignant settings—such as chronic lymphocytic leukemia—the combination of IL‑21 with CD40 ligand drives leukemic cell proliferation and differentiation, and similarly, its incorporation into adoptive T cell immunotherapy protocols bolsters the formation of durable memory phenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, IL‑21 functions within complex regulatory networks by interacting with other cytokines and signaling pathways. It can induce IL‑10 production—thereby exerting immunosuppressive effects—and, by triggering IL‑22 production through STAT3‐dependent epigenetic remodeling, it helps fine‑tune mucosal immunity. Moreover, IL‑21 and its receptor are expressed by epithelial cells in the gut, where its dysregulation is linked to inflammatory bowel disease, and its increased expression is observed in IgG4‑related disorders and psoriasis. Collectively, these interactions—with factors such as IL‑27, TGF‑β, and costimulatory molecules—not only influence the balance between pro‑inflammatory and regulatory responses in infections and autoimmunity but also affect tumor progression and therapeutic outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "29", "end_ref": "35"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Warren J Leonard, Rosanne Spolski "}, {"type": "b", "children": [{"type": "t", "text": "Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Immunol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nri1688"}], "href": "https://doi.org/10.1038/nri1688"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16138102"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16138102"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Katsutoshi Ozaki, Rosanne Spolski, Rachel Ettinger, et al. 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Synonyms CVID11, ZA11
Proteins IL21_HUMAN
NCBI Gene ID 59067
API
Download Associations
Predicted Functions View IL21's ARCHS4 Predicted Functions.
Co-expressed Genes View IL21's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View IL21's ARCHS4 Predicted Functions.

Functional Associations

IL21 has 4,568 functional associations with biological entities spanning 8 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) extracted from 89 datasets.

Click the + buttons to view associations for IL21 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Achilles Cell Line Gene Essentiality Profiles cell lines with fitness changed by IL21 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles tissues with high or low expression of IL21 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of IL21 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of IL21 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 IL21 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 IL21 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 IL21 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of IL21 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 IL21 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with IL21 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 IL21 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of IL21 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 IL21 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 IL21 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing IL21 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing IL21 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with IL21 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 IL21 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with IL21 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with IL21 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with IL21 gene/protein from the curated CTD Gene-Disease Associations dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by IL21 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Curated Gene-Disease Association Evidence Scores diseases involving IL21 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
DISEASES Curated Gene-Disease Association Evidence Scores 2025 diseases involving IL21 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores diseases associated with IL21 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 IL21 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 IL21 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 IL21 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 IL21 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with IL21 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 IL21 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 IL21 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of IL21 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
GAD Gene-Disease Associations diseases associated with IL21 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GAD High Level Gene-Disease Associations diseases associated with IL21 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
GDSC Cell Line Gene Expression Profiles cell lines with high or low expression of IL21 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with IL21 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 IL21 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of IL21 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of IL21 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of IL21 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of IL21 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of IL21 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of IL21 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving IL21 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving IL21 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving IL21 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing IL21 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by IL21 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by IL21 gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by IL21 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of IL21 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of IL21 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GWASdb SNP-Disease Associations diseases associated with IL21 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with IL21 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of IL21 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HPO Gene-Disease Associations phenotypes associated with IL21 gene by mapping known disease genes to disease phenotypes from the HPO Gene-Disease Associations dataset.
HuBMAP Azimuth Cell Type Annotations cell types associated with IL21 gene from the HuBMAP Azimuth Cell Type Annotations dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with IL21 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
IMPC Knockout Mouse Phenotypes phenotypes of mice caused by IL21 gene knockout from the IMPC Knockout Mouse Phenotypes dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for IL21 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of IL21 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
KEGG Pathways pathways involving IL21 protein from the KEGG Pathways dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of IL21 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of IL21 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of IL21 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain IL21 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by IL21 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of IL21 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MPO Gene-Phenotype Associations phenotypes of transgenic mice caused by IL21 gene mutations from the MPO Gene-Phenotype Associations dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of IL21 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
OMIM Gene-Disease Associations phenotypes associated with IL21 gene from the curated OMIM Gene-Disease Associations dataset.
PANTHER Pathways pathways involving IL21 protein from the PANTHER Pathways dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for IL21 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of IL21 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of IL21 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving IL21 protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving IL21 protein from the Wikipathways PFOCR 2024 dataset.
Reactome Pathways 2024 pathways involving IL21 protein from the Reactome Pathways 2024 dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at IL21 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of IL21 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of IL21 gene from the RummaGEO Gene Perturbation Signatures dataset.
Tabula Sapiens Gene-Cell Associations cell types with high or low expression of IL21 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of IL21 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of IL21 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with IL21 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with IL21 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2014 pathways involving IL21 protein from the Wikipathways Pathways 2014 dataset.
WikiPathways Pathways 2024 pathways involving IL21 protein from the WikiPathways Pathways 2024 dataset.