IL6R Gene
Interleukin 6 Receptor: Key Mediator of IL-6 Signaling and Inflammatory Pathways
Gene Information Card
| Symbol | IL6R |
|---|---|
| Full Name | Interleukin 6 Receptor |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 3570 ncbi.nlm.nih.gov/gene/3570 |
| Ensembl ID | ENSG00000160712 |
| UniProt ID | P08887 |
| OMIM ID | 147880 |
| HGNC ID | 6019 |
| Aliases | CD126, IL6RA, IL6RQ, gp80 |
Description
The IL6R gene encodes the interleukin 6 receptor alpha subunit (IL-6Rα), a type I cytokine receptor that binds interleukin 6 (IL-6) with high affinity. Upon IL-6 binding, IL-6R associates with the signal-transducing subunit gp130 (IL6ST) to activate JAK-STAT3 signaling, regulating immune response, inflammation, hematopoiesis, and acute-phase reactions. Soluble IL-6R (sIL-6R) generated by proteolytic cleavage or alternative splicing can mediate trans-signaling, expanding IL-6 actions to cells lacking membrane-bound IL-6R.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid Arthritis | IL6R signaling drives synovial inflammation and joint destruction via STAT3 activation; IL-6R blockade is therapeutic | ClinVar, OMIM |
| Castleman Disease | Dysregulated IL-6/IL6R signaling promotes lymphoproliferation and systemic inflammation | OMIM, NCBI |
| Juvenile Idiopathic Arthritis | IL6R variants and elevated IL-6 contribute to chronic arthritis in children | ClinVar |
| Multiple Myeloma | IL-6R-mediated signaling supports myeloma cell growth and survival | COSMIC, NCBI |
| Cytokine Release Syndrome | IL-6/IL6R axis is central to CRS pathogenesis; tocilizumab (anti-IL6R) is used therapeutically | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 4.2 | Medium |
| Lung | 3.8 | Medium |
| Spleen | 6.1 | High |
| Bone Marrow | 5.5 | High |
| Blood | 7.0 | High |
| Kidney | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 4.5 | Hepatocyte line |
| THP-1 | 8.2 | Monocytic line |
| Jurkat | 1.3 | T-cell line |
| U937 | 7.8 | Myelomonocytic line |
| K562 | 3.0 | Erythroleukemia line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2228145 (Asp358Ala) | SNP | ~40% in European populations | Increases soluble IL-6R levels; associated with reduced risk of coronary artery disease and altered IL-6 signaling |
| rs4129267 | Intronic variant | ~35% | Linked to IL6R expression and inflammatory biomarker levels |
| c.488G>A (p.Arg163Gln) | Missense | Rare | Reduced IL-6 binding affinity; reported in atypical inflammatory conditions |
Mutation functional classification
Loss of Function (LOF)
rs2228145 (Asp358Ala) increases sIL-6R shedding, reducing membrane-bound IL-6R and dampening classical signaling; associated with lower CRP and cardiovascular risk.
Gain of Function (GOF)
Not well-documented; overexpression of IL6R in multiple myeloma contributes to enhanced STAT3 activation.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported in IL6R.
View complete mutation data：
Gene Ontology (GO)
Pathways
• IL-6 Signaling Pathway (Reactome: R-HSA-1059683)
• JAK-STAT Signaling Pathway (KEGG: hsa04630)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
• Interleukin-6 family signaling (Reactome: R-HSA-6783589)
Protein Summary
The IL-6 receptor alpha chain (IL-6Rα, CD126) is a 468-amino-acid transmembrane glycoprotein with an extracellular domain containing a cytokine-binding module and a fibronectin type III domain. It binds IL-6 with low affinity; high-affinity signaling requires association with gp130. The intracellular domain is short and lacks intrinsic kinase activity. Soluble IL-6R (sIL-6R) is generated by ADAM17-mediated shedding or alternative splicing and can activate trans-signaling in cells expressing gp130 only. IL-6R is a therapeutic target for tocilizumab and sarilumab in inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL6RA & IL6ST Overexpression U2OS Stable Cell Line | EDJ-GQ83 | Human | 3570 & 3572 | Details Get a Quote |
| IL6R Knockout HEK293 Cell Line | EDJ-KQ499 | Human | 3570 | Details Get a Quote |
| IL6R Knockout A-549 Cell Line | EDJ-KQ18812 | Human | 3570 | Details Get a Quote |
| IL6R Knockout HCT 116 Cell Line | EDJ-KQ18813 | Human | 3570 | Details Get a Quote |
| IL6R Knockout HeLa Cell Line | EDJ-KQ18814 | Human | 3570 | Details Get a Quote |
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