IL6ST Gene - Interleukin 6 Cytokine Family Signal Transducer
Comprehensive genomic and functional analysis of IL6ST, encoding gp130, a shared receptor for IL-6 family cytokines.
Gene Information Card
| Symbol | IL6ST |
|---|---|
| Full Name | Interleukin 6 Cytokine Family Signal Transducer |
| Gene Type | protein-coding |
| Chromosomal Location | 5q11.2 |
| NCBI Gene ID | 3572 ncbi.nlm.nih.gov/gene/3572 |
| Ensembl ID | ENSG00000134352 |
| UniProt ID | P40189 |
| OMIM ID | 600694 |
| HGNC ID | 6021 |
| Aliases | gp130, CD130, IL6R-beta |
Description
IL6ST (Interleukin 6 Cytokine Family Signal Transducer) encodes glycoprotein 130 (gp130), a transmembrane receptor that serves as the common signal-transducing subunit for the interleukin-6 (IL-6) family of cytokines, including IL-6, IL-11, LIF, OSM, CNTF, CT-1, and CLCF1. Upon ligand binding, gp130 homodimerizes or heterodimerizes with other receptor subunits, activating JAK/STAT and MAPK signaling pathways. This gene is essential for immune response, hematopoiesis, and neuronal development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Stüve-Wiedemann syndrome | Loss-of-function mutations in IL6ST impair gp130-mediated signaling, leading to skeletal dysplasia, autonomic dysfunction, and respiratory distress. | OMIM #601559 |
| Hyper-IgE syndrome (autosomal recessive) | Biallelic loss-of-function mutations disrupt IL-6/IL-11 signaling, causing elevated IgE, recurrent infections, and skeletal abnormalities. | ClinVar; PMID: 28166811 |
| Hepatocellular carcinoma | Gain-of-function mutations (e.g., p.Asn404Tyr) in the extracellular domain promote constitutive gp130 activation, driving STAT3-mediated oncogenesis. | COSMIC; PMID: 23542689 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Heart | 8.3 | Medium |
| Lung | 6.7 | Medium |
| Brain | 4.2 | Low |
| Kidney | 9.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.2 | Hepatocellular carcinoma cell line |
| A549 | 7.8 | Lung adenocarcinoma cell line |
| K562 | 5.3 | Chronic myeloid leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.700C>T (p.Arg234Cys) | Missense | <0.01% | Loss-of-function; associated with Stüve-Wiedemann syndrome |
| c.1210A>T (p.Asn404Tyr) | Missense | <0.01% | Gain-of-function; found in hepatocellular carcinoma |
| c.1720_1721del (p.Leu574fs) | Frameshift | <0.01% | Loss-of-function; causes hyper-IgE syndrome |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations in IL6ST cause Stüve-Wiedemann syndrome and autosomal recessive hyper-IgE syndrome by disrupting gp130-mediated JAK/STAT signaling.
Gain of Function (GOF)
Somatic gain-of-function mutations (e.g., p.Asn404Tyr) in the extracellular domain lead to constitutive gp130 dimerization and STAT3 hyperactivation, promoting tumorigenesis.
Dominant Negative (DN)
Dominant-negative mutations have not been clearly described for IL6ST; most pathogenic variants are recessive or somatic.
View complete mutation data：
Gene Ontology (GO)
Pathways
• IL-6 signaling pathway (KEGG: hsa04630)
• JAK-STAT signaling pathway (KEGG: hsa04630)
• IL-11 signaling pathway (Reactome: R-HSA-447115)
Protein Summary
The IL6ST protein (gp130) is a 918-amino-acid type I transmembrane glycoprotein with an extracellular domain containing six fibronectin type III domains and a cytoplasmic region harboring conserved Box1/Box2 motifs for JAK binding. It functions as the signal-transducing subunit for all IL-6 family cytokines. Upon cytokine binding, gp130 forms homodimers or heterodimers with LIFR or OSMR, activating JAK1, JAK2, and TYK2, which phosphorylate STAT3 and STAT1. gp130 is widely expressed and critical for immune regulation, liver regeneration, and neuronal survival.
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 |
| 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 |
| IL6ST Knockout NCI-H1299 Cell Line | EDJ-KZ3 | Human | 3572 | Details Get a Quote |
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