IL27RA Gene: Interleukin-27 Receptor Subunit Alpha - Function, Disease Associations, and Expression
Comprehensive biomedical overview of IL27RA (WSX1), a key cytokine receptor subunit involved in immune regulation, with clinical implications in infectious diseases and cancer.
Gene Information Card
| Symbol | IL27RA |
|---|---|
| Full Name | Interleukin 27 receptor subunit alpha |
| Gene Type | protein coding |
| Chromosomal Location | 19p13.11 |
| NCBI Gene ID | 9466 ncbi.nlm.nih.gov/gene/9466 |
| Ensembl ID | ENSG00000104998 |
| UniProt ID | Q6UWB1 |
| OMIM ID | 605350 |
| HGNC ID | 17299 |
| Aliases | WSX1, IL27R, TCCR, zcytor1 |
Description
IL27RA encodes the interleukin-27 receptor subunit alpha (also known as WSX1), a type I cytokine receptor that pairs with gp130 (IL6ST) to form the functional IL-27 receptor complex. This receptor is primarily expressed on immune cells, including T cells, natural killer (NK) cells, and monocytes, and plays a critical role in regulating inflammatory and anti-inflammatory responses. IL27RA signaling activates JAK-STAT pathways, particularly STAT1 and STAT3, influencing T helper cell differentiation, cytokine production, and antiviral responses. The gene is located on chromosome 19p13.11 and is implicated in various diseases, including infectious diseases, autoimmune conditions, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Viral infections (e.g., influenza, HIV) | IL27RA mediates antiviral immune responses via STAT1 activation and interferon-like signaling; deficiency may impair viral clearance. | ClinVar and literature reports (e.g., PMID: 21727189) |
| Inflammatory bowel disease (IBD) | IL27RA signaling modulates intestinal inflammation; altered expression or variants may affect susceptibility. | ClinVar and GWAS studies (e.g., PMID: 21102463) |
| Cancer (e.g., colorectal, breast) | IL27RA can exert anti-tumor effects by promoting cytotoxic T cell responses; aberrant expression may influence tumor microenvironment. | COSMIC mutation data and expression studies (e.g., PMID: 25605292) |
| Asthma and allergic diseases | IL27RA influences Th2/Th17 balance; dysregulation may contribute to airway inflammation. | Literature evidence (e.g., PMID: 20628019) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.3 | Medium |
| Spleen | 11.8 | Medium |
| Bone marrow | 9.5 | Low |
| Lung | 6.2 | Low |
| Liver | 3.1 | Not detected |
| Brain | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | 15.2 | High expression; used as model for monocyte/macrophage function |
| Jurkat (T cell leukemia) | 8.7 | Moderate expression; relevant for T cell signaling studies |
| A549 (lung carcinoma) | 4.3 | Low expression; may be induced by inflammatory stimuli |
| MCF7 (breast carcinoma) | 2.1 | Low expression; potential role in tumor immunity |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.589G>A (p.Ala197Thr) | Missense | 0.01% (gnomAD) | Potential impact on receptor dimerization; clinical significance uncertain |
| c.1123C>T (p.Arg375Trp) | Missense | 0.005% (gnomAD) | Located in cytoplasmic domain; may affect STAT binding |
| c.1465_1466del (p.Leu489fs) | Frameshift | Rare | Predicted loss-of-function; associated with immunodeficiency in case reports |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the cytoplasmic domain impair JAK-STAT signaling, leading to reduced immune responses and increased susceptibility to infections.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some missense variants may enhance receptor stability but functional data are lacking.
Dominant Negative (DN)
Certain missense mutations in the extracellular domain may disrupt dimerization with gp130, potentially exerting a dominant-negative effect on IL-27 signaling.
View complete mutation data：
Gene Ontology (GO)
| • interleukin-27 receptor activity | • cytokine receptor activity |
| • protein homodimerization activity | • protein heterodimerization activity |
| • signal transducer activity | • plasma membrane |
| • integral component of plasma membrane | • JAK-STAT cascade |
| • positive regulation of T cell proliferation | • negative regulation of inflammatory response |
Pathways
• IL-27 signaling pathway (Reactome: R-HSA-9020958)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
• JAK-STAT signaling pathway (KEGG: hsa04630)
• Th1 and Th2 cell differentiation (KEGG: hsa04658)
Protein Summary
The IL27RA protein (UniProt Q6UWB1) is a 636-amino acid type I transmembrane glycoprotein with a signal peptide, an extracellular domain containing two fibronectin type III domains and a WSXWS motif, a single transmembrane helix, and a cytoplasmic tail with conserved Box1/Box2 motifs for JAK binding. It forms a heterodimer with gp130 (IL6ST) to create the high-affinity IL-27 receptor. Upon IL-27 binding, the receptor activates JAK1/JAK2 and TYK2, leading to phosphorylation of STAT1 and STAT3, which translocate to the nucleus to regulate gene expression. IL27RA is crucial for the differentiation of Th1 cells, suppression of Th17 responses, and antiviral immunity. Its expression is inducible by cytokines and microbial stimuli.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL27RA Knockout HEK293 Cell Line | EDJ-KQ492 | Human | 9466 | Details Get a Quote |
| IL27RA Knockout A-549 Cell Line | EDJ-KQ18805 | Human | 9466 | Details Get a Quote |
| IL27RA Knockout HCT 116 Cell Line | EDJ-KQ18806 | Human | 9466 | Details Get a Quote |
| IL27RA Knockout HeLa Cell Line | EDJ-KQ18807 | Human | 9466 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
