IL6 Gene - Interleukin 6 (IL-6) | Function, Disease Associations & Expression
Comprehensive biomedical resource for the IL6 gene, covering genomic context, protein function, tissue expression, disease mechanisms, and clinical significance.
Gene Information Card
| Symbol | IL6 |
|---|---|
| Full Name | Interleukin 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 7p15.3 |
| NCBI Gene ID | 3569 ncbi.nlm.nih.gov/gene/3569 |
| Ensembl ID | ENSG00000136244 |
| UniProt ID | P05231 |
| OMIM ID | 147620 |
| HGNC ID | 6018 |
| Aliases | BSF2, HGF, HSF, IFNB2, IL-6, B-cell stimulatory factor 2, hybridoma growth factor |
Description
The IL6 gene encodes Interleukin-6 (IL-6), a pleiotropic cytokine with critical roles in immune regulation, inflammation, hematopoiesis, and oncogenesis. It is produced by various cell types including T-cells, macrophages, fibroblasts, and endothelial cells. IL-6 exerts its effects through a receptor complex consisting of IL-6R (CD126) and gp130 (IL6ST), activating the JAK-STAT3, MAPK, and PI3K-Akt signaling pathways. Dysregulation of IL-6 expression is implicated in chronic inflammation, autoimmune diseases, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid Arthritis | Elevated IL-6 promotes synovial inflammation, autoantibody production, and joint destruction via STAT3 activation. | Strong evidence from GWAS, clinical trials with tocilizumab (anti-IL-6R) showing efficacy. |
| Castleman Disease | IL-6 overproduction drives systemic inflammatory symptoms and lymphoproliferation. | Direct evidence from clinical response to siltuximab (anti-IL-6) and elevated serum IL-6 levels. |
| Cytokine Release Syndrome (CRS) | Massive IL-6 release during CAR-T therapy or infections triggers systemic inflammation and multi-organ dysfunction. | Clinical evidence from tocilizumab use in CRS management. |
| Juvenile Idiopathic Arthritis (JIA) | IL-6 contributes to systemic inflammation and growth retardation in affected children. | Clinical trials with tocilizumab show significant improvement. |
| Multiple Myeloma | IL-6 acts as a growth and survival factor for myeloma cells via autocrine/paracrine loops. | In vitro and in vivo studies demonstrate IL-6 dependence of myeloma cell lines. |
| Anaplastic Large Cell Lymphoma (ALCL) | IL-6 autocrine signaling promotes tumor cell proliferation and survival. | Preclinical studies show IL-6 pathway activation in ALCL cell lines. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose Tissue | ~10.2 | Medium |
| Spleen | ~8.5 | Medium |
| Lung | ~6.1 | Low |
| Liver | ~3.4 | Low |
| Bone Marrow | ~2.8 | Low |
| Brain | ~1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (Monocyte) | ~15.3 | High baseline; inducible by LPS |
| HUVEC (Endothelial) | ~8.7 | Inducible by TNF-α and IL-1β |
| HeLa (Cervical) | ~2.1 | Low baseline; inducible by IL-1 |
| A549 (Lung) | ~1.8 | Low baseline; inducible by IL-1β |
| MCF7 (Breast) | ~0.9 | Very low baseline |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1800795 (-174G>C) | SNP (Promoter) | ~40% (C allele) | Affects IL-6 transcription; associated with inflammatory disease susceptibility and differential outcomes in sepsis. |
| rs1800796 (-572G>C) | SNP (Promoter) | ~15% (C allele) | Linked to altered IL-6 levels and risk for coronary artery disease. |
| rs2069845 (p.Phe257Leu) | Missense | ~5% | Potential impact on protein stability; clinical significance unclear. |
| rs2069840 (p.Val168Ile) | Missense | ~8% | May affect receptor binding; functional studies limited. |
Mutation functional classification
Loss of Function (LOF)
Complete loss-of-function mutations in IL6 are extremely rare and not well-documented in humans. Animal models (IL6 knockout mice) show impaired immune responses, reduced inflammation, and altered hematopoiesis.
Gain of Function (GOF)
Gain-of-function is primarily achieved through overexpression (e.g., promoter SNPs increasing transcription) rather than coding mutations. This leads to chronic inflammation and contributes to autoimmune and malignant diseases.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for IL6. The cytokine functions as a soluble ligand, and its receptor complex is the primary target for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005125 - cytokine activity | • GO:0008083 - growth factor activity |
| • GO:0005515 - protein binding | • GO:0005615 - extracellular space |
| • GO:0006954 - inflammatory response | • GO:0006955 - immune response |
| • GO:0045944 - positive regulation of transcription by RNA polymerase II | • GO:0035556 - intracellular signal transduction |
Pathways
• IL-6 signaling pathway (KEGG hsa04630)
• JAK-STAT signaling pathway (KEGG hsa04630)
• Cytokine-cytokine receptor interaction (KEGG hsa04060)
• Inflammatory bowel disease (KEGG hsa05321)
• Rheumatoid arthritis (KEGG hsa05323)
• Toll-like receptor signaling pathway (KEGG hsa04620)
Protein Summary
Interleukin-6 (IL-6) is a 21-28 kDa glycosylated cytokine composed of 212 amino acids (precursor) and 184 amino acids (mature form). It adopts a four-helix bundle structure typical of the IL-6 family. IL-6 binds to the membrane-bound IL-6 receptor (IL-6R) or soluble IL-6R (sIL-6R), and the complex then associates with the signal-transducing subunit gp130. This triggers JAK1/JAK2/TYK2 phosphorylation, leading to STAT3 activation and downstream gene transcription. IL-6 also activates the MAPK and PI3K-Akt pathways. Its half-life in circulation is approximately 2 hours, and it is primarily cleared by hepatocytes and renal filtration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OSMR & IL6ST Overexpression U2OS Stable Cell Line | EDJ-GQ82 | Human | 9180 & 3572 | Details Get a Quote |
| IL6RA & IL6ST Overexpression U2OS Stable Cell Line | EDJ-GQ83 | Human | 3570 & 3572 | Details Get a Quote |
| IL6ST Knockout HEK293 Cell Line | EDJ-KQ134 | Human | 3572 | Details Get a Quote |
| IL6 Knockout HEK293 Cell Line | EDJ-KQ498 | Human | 3569 | Details Get a Quote |
| IL6R Knockout HEK293 Cell Line | EDJ-KQ499 | Human | 3570 | Details Get a Quote |
| PPIL6 Knockout HEK293 Cell Line | EDJ-KQ14855 | Human | 285755 | Details Get a Quote |
| IL6 Knockout A-549 Cell Line | EDJ-KQ18810 | Human | 3569 | Details Get a Quote |
| IL6 Knockout HeLa Cell Line | EDJ-KQ18811 | Human | 3569 | 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 |
| IL6ST Knockout A-549 Cell Line | EDJ-KQ18815 | Human | 3572 | Details Get a Quote |
| IL6ST Knockout HCT 116 Cell Line | EDJ-KQ18816 | Human | 3572 | Details Get a Quote |
| IL6ST Knockout HeLa Cell Line | EDJ-KQ18817 | Human | 3572 | Details Get a Quote |
| PPIL6 Knockout A-549 Cell Line | EDJ-KQ45294 | Human | 285755 | Details Get a Quote |
Displaying Records 1 To 15 Of 19 Records
