IL15RA Gene - Interleukin 15 Receptor Subunit Alpha
Essential regulator of IL-15 signaling in immune cell homeostasis and disease
Gene Information Card
| Symbol | IL15RA |
|---|---|
| Full Name | Interleukin 15 Receptor Subunit Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 10p15.1 |
| NCBI Gene ID | 3601 ncbi.nlm.nih.gov/gene/3601 |
| Ensembl ID | ENSG00000134470 |
| UniProt ID | Q13261 |
| OMIM ID | 601070 |
| HGNC ID | 5978 |
| Aliases | IL-15Rα, IL15R, sIL-15Rα |
Description
The IL15RA gene encodes the alpha subunit of the interleukin-15 receptor (IL-15Rα). This high-affinity receptor component is essential for IL-15 binding, trans-presentation, and signaling. IL-15Rα is expressed on various immune cells including NK cells, T cells, and dendritic cells, and plays a critical role in the development, survival, and activation of NK and memory CD8+ T cells. The gene produces multiple splice variants, including a soluble form that can modulate IL-15 activity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Celiac disease | IL15RA variants alter IL-15 trans-presentation, enhancing intraepithelial lymphocyte activation and intestinal inflammation | GWAS (PMID: 20190752) |
| Rheumatoid arthritis | Polymorphisms in IL15RA are associated with increased IL-15 signaling and synovial inflammation | GWAS (PMID: 24390342) |
| Multiple sclerosis | IL15RA variants influence IL-15-mediated T cell and NK cell homeostasis, contributing to autoimmune demyelination | GWAS (PMID: 21833088) |
| Acute lymphoblastic leukemia (ALL) | IL15RA overexpression provides survival signals to leukemic cells via JAK-STAT pathway activation | Expression studies (PMID: 16912224) |
| Inflammatory bowel disease (IBD) | IL15RA polymorphisms linked to altered IL-15 signaling and mucosal immune dysregulation | GWAS (PMID: 26192919) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.3 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 8.5 | Medium |
| Lung | 4.2 | Low |
| Small intestine | 3.9 | Low |
| Colon | 3.1 | Low |
| Skin | 2.5 | Low |
| Brain | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NK-92 (NK cell line) | 15.2 | High expression |
| Jurkat (T cell line) | 9.7 | Moderate expression |
| THP-1 (monocyte line) | 6.4 | Moderate expression |
| HEK293 (embryonic kidney) | 2.1 | Low expression |
| HeLa (cervical cancer) | 1.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2228059 (Asn386Ser) | Missense | 0.15 (global) | Alters IL-15 binding affinity; associated with autoimmune disease risk |
| rs3136617 (intronic) | Intronic variant | 0.22 (global) | Linked to altered splicing and IL15RA expression levels |
| rs2296135 (5' UTR) | Regulatory | 0.18 (global) | Affects transcription factor binding; associated with celiac disease |
| c.1-79C>T | Promoter variant | Rare | Reduces promoter activity; reported in inflammatory conditions |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in IL15RA impair IL-15 trans-presentation, leading to reduced NK cell survival and defective memory CD8+ T cell maintenance. Such variants are rare and associated with immunodeficiency phenotypes.
Gain of Function (GOF)
Gain-of-function mutations (e.g., overexpression or activating missense variants) enhance IL-15 signaling, promoting excessive T cell and NK cell proliferation. These are observed in certain leukemias and autoimmune conditions.
Dominant Negative (DN)
Dominant-negative splice variants encoding truncated IL-15Rα can sequester IL-15 or interfere with wild-type receptor assembly, reducing functional signaling. These have been reported in inflammatory diseases.
View complete mutation data：
Gene Ontology (GO)
| • cytokine receptor activity (GO:0004896) | • protein binding (GO:0005515) |
| • integral component of membrane (GO:0016021) | • interleukin-15-mediated signaling pathway (GO:0038110) |
| • positive regulation of T cell proliferation (GO:0042102) | • innate immune response (GO:0045087) |
| • signal transduction (GO:0007165) |
Pathways
• Interleukin-15 signaling (Reactome: R-HSA-8984722)
• JAK-STAT signaling pathway (KEGG: hsa04630)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
• NK cell mediated cytotoxicity (KEGG: hsa04650)
Protein Summary
The IL-15 receptor alpha subunit (UniProt Q13261) is a 267-amino acid type I transmembrane glycoprotein. It consists of an extracellular sushi domain (required for IL-15 binding), a transmembrane region, and a short cytoplasmic tail. The protein is expressed on antigen-presenting cells and activated immune cells. IL-15Rα binds IL-15 with high affinity (Kd ~10 pM) and presents it in trans to neighboring cells expressing the IL-2/15Rβγc complex. This trans-presentation mechanism is essential for IL-15 biological activity. Alternative splicing generates multiple isoforms, including a soluble form that can antagonize IL-15 signaling. Post-translational modifications include N-glycosylation and ubiquitination, which regulate receptor stability and turnover.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL15RA Knockout HEK293 Cell Line | EDJ-KQ485 | Human | 3601 | Details Get a Quote |
| IL15RA Knockout A-549 Cell Line | EDJ-KQ18797 | Human | 3601 | Details Get a Quote |
| IL15RA Knockout HCT 116 Cell Line | EDJ-KQ18798 | Human | 3601 | Details Get a Quote |
| IL15RA Knockout HeLa Cell Line | EDJ-KQ18799 | Human | 3601 | Details Get a Quote |
