IL23R Gene: Interleukin-23 Receptor – Function, Disease Associations, and Clinical Significance
Comprehensive biomedical overview of the IL23R gene, including genomic context, expression, mutations, and disease links.
Gene Information Card
| Symbol | IL23R |
|---|---|
| Full Name | Interleukin 23 receptor |
| Gene Type | protein coding |
| Chromosomal Location | 1p31.3 |
| NCBI Gene ID | 149233 ncbi.nlm.nih.gov/gene/149233 |
| Ensembl ID | ENSG00000162594 |
| UniProt ID | Q5VWK5 |
| OMIM ID | 607562 |
| HGNC ID | 19100 |
| Aliases | IL-23 receptor; IL23R; IL-23R |
Description
The IL23R gene encodes the alpha subunit of the interleukin-23 receptor, a heterodimeric complex that also includes the IL12RB1 subunit. IL23R is expressed on various immune cells, including T cells, NK cells, and innate lymphoid cells, and plays a critical role in the differentiation and maintenance of Th17 cells. Signaling through IL23R activates the JAK-STAT pathway, particularly STAT3, leading to pro-inflammatory cytokine production. Genetic variants in IL23R are strongly associated with susceptibility to inflammatory and autoimmune diseases, including inflammatory bowel disease (Crohn's disease and ulcerative colitis), psoriasis, ankylosing spondylitis, and multiple sclerosis. The receptor is also implicated in cancer, where its expression can modulate tumor immunity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory Bowel Disease (Crohn's disease, ulcerative colitis) | IL23R variants alter receptor function and signaling, affecting Th17 cell responses and mucosal immunity. The protective variant R381Q reduces IL-23-induced STAT3 phosphorylation and Th17 effector function. | ClinVar, multiple GWAS studies (e.g., Duerr et al. 2006, Anderson et al. 2011) |
| Psoriasis | IL23R signaling promotes IL-17 production by T cells, driving skin inflammation. Risk alleles increase IL23R expression or signaling. | ClinVar, GWAS (Tsoi et al. 2012) |
| Ankylosing Spondylitis | IL23R variants contribute to IL-23/IL-17 axis dysregulation, leading to chronic inflammation in the spine and sacroiliac joints. | ClinVar, GWAS (Wellcome Trust Case Control Consortium; Burton et al. 2007) |
| Multiple Sclerosis | IL23R signaling supports Th17 cell pathogenicity, which is implicated in autoimmune demyelination. Certain IL23R alleles modulate disease risk. | ClinVar, GWAS (International Multiple Sclerosis Genetics Consortium) |
| Colorectal Cancer | IL23R expression in tumor-infiltrating immune cells can influence anti-tumor immunity. Some variants may affect cancer risk or progression. | COSMIC, literature (e.g., Langowski et al. 2006) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 5.2 | Medium |
| Spleen | 4.8 | Medium |
| Bone marrow | 3.1 | Low |
| Appendix | 2.9 | Low |
| Lung | 1.5 | Low |
| Small intestine | 1.2 | Low |
| Colon | 1.0 | Low |
| Blood | 0.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Th17 cells | High | IL23R is highly expressed on Th17 cells, essential for their effector function. |
| NK cells | Medium | IL23R expression on NK cells modulates IFN-gamma production. |
| Gamma-delta T cells | Medium | IL23R is expressed on gamma-delta T cells, contributing to IL-17 production. |
| Innate lymphoid cells (ILC3) | High | ILC3s express IL23R and respond to IL-23 to produce IL-22 and IL-17. |
| Macrophages | Low | IL23R expression is low but can be induced upon activation. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R381Q (rs11209026) | Missense | ~5-10% in European populations | Protective against IBD and psoriasis; reduces IL-23-induced STAT3 phosphorylation and Th17 responses. |
| V362I (rs7530511) | Missense | ~10-15% | Associated with increased risk of ulcerative colitis; functional impact unclear. |
| G149R (rs11465804) | Missense | Rare | Loss-of-function; associated with reduced IL-23 signaling and protection against IBD. |
| c.1150C>T (p.R384W) | Missense | Rare | Reported in ClinVar as likely pathogenic; affects receptor function. |
| c.298G>A (p.V100M) | Missense | Rare | Uncertain significance; may affect protein stability. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in IL23R, such as R381Q and G149R, reduce IL-23-mediated signaling, leading to decreased Th17 cell differentiation and pro-inflammatory cytokine production. These variants are generally protective against autoimmune diseases like IBD and psoriasis.
Gain of Function (GOF)
Gain-of-function mutations in IL23R are less well-characterized. Some variants may increase receptor expression or signaling, enhancing Th17 responses and increasing susceptibility to inflammatory diseases. However, specific gain-of-function mutations have not been extensively validated in clinical databases.
Dominant Negative (DN)
Dominant-negative effects have not been clearly documented for IL23R mutations. However, since IL23R forms a heterodimer with IL12RB1, certain mutations might interfere with complex assembly or signaling, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • interleukin-23 receptor activity | • interleukin-23 binding |
| • protein homodimerization activity | • protein heterodimerization activity |
| • signal transducer activity | • cell surface receptor signaling pathway |
| • JAK-STAT cascade | • positive regulation of T cell proliferation |
| • positive regulation of cytokine production | • immune response |
| • inflammatory response | • Th17 cell differentiation |
Pathways
• IL-23 signaling pathway
• JAK-STAT signaling pathway
• Th17 cell differentiation
• Cytokine-cytokine receptor interaction
• Inflammatory bowel disease (IBD) pathway
• Autoimmune thyroid disease pathway
Protein Summary
The IL23R protein is a type I transmembrane glycoprotein that serves as the ligand-binding subunit of the interleukin-23 receptor complex. It consists of an extracellular domain with fibronectin type III domains, a transmembrane region, and a cytoplasmic tail containing Box1/Box2 motifs for JAK2 association. Upon IL-23 binding, IL23R associates with IL12RB1, activating JAK2 and TYK2, leading to STAT3 phosphorylation and downstream gene transcription. IL23R is crucial for the survival, expansion, and effector function of Th17 cells, which produce IL-17A, IL-17F, IL-22, and other pro-inflammatory cytokines. The receptor is also expressed on other immune cells, including NK cells, gamma-delta T cells, and ILC3s, contributing to mucosal immunity and inflammation. Alternative splicing generates multiple isoforms, some of which are soluble and may act as decoy receptors. Post-translational modifications, such as glycosylation, are essential for proper protein folding and ligand binding.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL23R Knockout HEK293 Cell Line | EDJ-KQ11016 | Human | 149233 | Details Get a Quote |
| IL23R Knockout HeLa Cell Line | EDJ-KQ58624 | Human | 149233 | Details Get a Quote |
| IL23R Knockout A-549 Cell Line | EDJ-KQ67106 | Human | 149233 | Details Get a Quote |
| IL23R Knockout HCT 116 Cell Line | EDJ-KQ75515 | Human | 149233 | Details Get a Quote |
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