IL21 Gene - Interleukin 21
Cytokine with pleiotropic roles in immunity and disease
Gene Information Card
| Symbol | IL21 |
|---|---|
| Full Name | Interleukin 21 |
| Gene Type | protein-coding |
| Chromosomal Location | 4q27 |
| NCBI Gene ID | 59067 ncbi.nlm.nih.gov/gene/59067 |
| Ensembl ID | ENSG00000138684 |
| UniProt ID | Q9HBE4 |
| OMIM ID | 605384 |
| HGNC ID | 6005 |
| Aliases | IL-21; Za11 |
Description
The IL21 gene encodes a cytokine that belongs to the common gamma-chain family of cytokines. It is primarily produced by CD4+ T cells, natural killer T cells, and follicular helper T cells. IL21 exerts pleiotropic effects on multiple immune cell types, including B cells, T cells, natural killer cells, and dendritic cells, regulating both innate and adaptive immune responses. It plays critical roles in immunoglobulin production, T cell differentiation, and antitumor immunity. Dysregulation of IL21 signaling is implicated in autoimmune diseases, immunodeficiencies, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Common variable immunodeficiency (CVID) | Loss-of-function mutations in IL21 lead to impaired T cell help and B cell differentiation, causing antibody deficiency. | OMIM; PMID: 23954330 |
| Inflammatory bowel disease (IBD) | IL21 is overexpressed in inflamed intestinal mucosa, promoting Th17 responses and mucosal inflammation. | PMID: 19505981 |
| Systemic lupus erythematosus (SLE) | Elevated IL21 levels contribute to B cell hyperactivity and autoantibody production. | PMID: 21931323 |
| Rheumatoid arthritis (RA) | IL21 enhances Th17 differentiation and osteoclastogenesis, exacerbating joint inflammation. | PMID: 20585057 |
| Cancer (e.g., melanoma, renal cell carcinoma) | IL21 can promote antitumor immunity by enhancing CD8+ T cell and NK cell cytotoxicity, but may also support tumor progression in some contexts. | PMID: 20534348 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 0.4 | Low |
| Spleen | 0.3 | Low |
| Bone marrow | 0.2 | Low |
| Thymus | 0.1 | Low |
| Other tissues | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| CD4+ T cells (activated) | Not available | High expression upon activation |
| Follicular helper T cells (Tfh) | Not available | High expression |
| Natural killer T cells | Not available | Moderate expression |
| Th17 cells | Not available | High expression |
| B cells | Not available | Low/absent |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.227C>T (p.Pro76Leu) | Missense | Rare | Loss of function; associated with CVID |
| c.289A>G (p.Thr97Ala) | Missense | Rare | Loss of function; impaired receptor binding |
| c.331C>T (p.Arg111Trp) | Missense | Rare | Loss of function; reduced secretion |
| c.400G>A (p.Val134Ile) | Missense | Rare | Uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair IL21 secretion, receptor binding, or signaling lead to immunodeficiency, particularly CVID.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression is associated with autoimmune diseases.
Dominant Negative (DN)
Not documented for IL21; mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • cytokine activity | • interleukin-21 receptor binding |
| • immune response | • regulation of cell proliferation |
| • positive regulation of B cell proliferation | • positive regulation of T cell proliferation |
| • positive regulation of immunoglobulin production |
Pathways
• Cytokine-cytokine receptor interaction
• Jak-STAT signaling pathway
• T cell receptor signaling pathway
• B cell receptor signaling pathway
• Th17 cell differentiation
Protein Summary
IL21 is a 131-amino acid cytokine with a four-helix bundle structure. It signals through a heterodimeric receptor composed of IL21R and the common gamma chain (γc), activating JAK1/JAK3 and STAT3/STAT5 pathways. IL21 regulates the differentiation, proliferation, and effector functions of multiple immune cells, including promoting B cell differentiation into plasma cells, enhancing CD8+ T cell and NK cell cytotoxicity, and driving Th17 differentiation. Its pleiotropic actions make it a key modulator of immunity and a therapeutic target in autoimmune diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL21R Knockout HEK293 Cell Line | EDJ-KQ488 | Human | 50615 | Details Get a Quote |
| IL21 Knockout HEK293 Cell Line | EDJ-KQ2181 | Human | 59067 | Details Get a Quote |
| IL21R Knockout HeLa Cell Line | EDJ-KQ56173 | Human | 50615 | Details Get a Quote |
| IL21 Knockout HeLa Cell Line | EDJ-KQ56956 | Human | 59067 | Details Get a Quote |
| IL21R Knockout A-549 Cell Line | EDJ-KQ64663 | Human | 50615 | Details Get a Quote |
| IL21 Knockout A-549 Cell Line | EDJ-KQ65462 | Human | 59067 | Details Get a Quote |
| IL21R Knockout HCT 116 Cell Line | EDJ-KQ73112 | Human | 50615 | Details Get a Quote |
| IL21 Knockout HCT 116 Cell Line | EDJ-KQ73898 | Human | 59067 | Details Get a Quote |
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