IL6ST Gene

HGNC Family	CD molecules (CD), Interleukin receptors, Fibronectin type III domain containing
Name	interleukin 6 signal transducer
Description	The protein encoded by this gene is a signal transducer shared by many cytokines, including interleukin 6 (IL6), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and oncostatin M (OSM). This protein functions as a part of the cytokine receptor complex. The activation of this protein is dependent upon the binding of cytokines to their receptors. vIL6, a protein related to IL6 and encoded by the Kaposi sarcoma-associated herpesvirus, can bypass the interleukin 6 receptor (IL6R) and directly activate this protein. Knockout studies in mice suggest that this gene plays a critical role in regulating myocyte apoptosis. Alternatively spliced transcript variants have been described. A related pseudogene has been identified on chromosome 17. [provided by RefSeq, May 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The interleukin‐6 signal transducer (IL6ST), also known as gp130, functions as the obligate receptor subunit for the IL‐6 family of cytokines and is a central mediator of inflammatory and immune signaling. Activation of IL6ST enables downstream Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathways – in particular STAT3 – which modulate cell proliferation, survival, and fate decisions in both immune cells and tumor cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Genetic studies have associated variants near IL6ST with immune‐mediated diseases such as rheumatoid arthritis, underscoring its role in immune regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, epigenetic modulation of the IL6ST promoter has been shown to affect its expression, suggesting that precise regulation of IL6ST levels is key to maintaining homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the oncologic context, gain‐of‐function mutations in IL6ST have been identified in inflammatory hepatocellular adenomas, where constitutive activation of gp130 drives ligand‐independent STAT3 signaling that is believed to contribute to tumor promotion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In parallel, modulation of IL6ST expression affects the differentiation of T helper cell subsets – for example, retroviral-mediated expression of IL6ST augmented Th17 development despite the presence of inhibitory signals"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and gp130 is also a component of unconventional receptor complexes, as seen in IL-35 signaling that mediates immune suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, IL6ST-mediated signaling contributes not only to cytokine-driven transcriptional responses but also to biophysical changes in cells – for instance, cytokine stimulation via IL6ST can trigger Rho-kinase–dependent actomyosin contractility that supports extracellular matrix remodeling, a process relevant to cell migration and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, IL6ST/gp130 is a pivotal mediator that integrates inflammatory signals to regulate immune cell differentiation and contributes to oncogenic processes through aberrant activation of the JAK/STAT axis. Its involvement in immune-mediated diseases and cancer highlights its potential as a therapeutic target for modulating inflammation and tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "4", "end_ref": "6"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hua Yu, Drew Pardoll, Richard Jove "}, {"type": "b", "children": [{"type": "t", "text": "STATs in cancer inflammation and immunity: a leading role for STAT3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Cancer (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nrc2734"}], "href": "https://doi.org/10.1038/nrc2734"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19851315"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19851315"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Victoria Sanz-Moreno, Cedric Gaggioli, Maggie Yeo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2011.06.018"}], "href": "https://doi.org/10.1016/j.ccr.2011.06.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21840487"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21840487"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mulugeta M Zegeye, Madelene Lindkvist, Knut Fälker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Commun Signal (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12964-018-0268-4"}], "href": "https://doi.org/10.1186/s12964-018-0268-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30185178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30185178"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Eli A Stahl, Soumya Raychaudhuri, Elaine F Remmers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.582"}], "href": "https://doi.org/10.1038/ng.582"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20453842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20453842"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Aleksandar Vojta, Paula Dobrinić, Vanja Tadić, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Repurposing the CRISPR-Cas9 system for targeted DNA methylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkw159"}], "href": "https://doi.org/10.1093/nar/gkw159"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26969735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26969735"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sandra Rebouissou, Mohamed Amessou, Gabrielle Couchy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature07475"}], "href": "https://doi.org/10.1038/nature07475"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19020503"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19020503"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Camilla Pilati, Mohamed Amessou, Michel P Bihl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20110283"}], "href": "https://doi.org/10.1084/jem.20110283"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21690253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21690253"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Wei Liao, Jian-Xin Lin, Lu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.2030"}], "href": "https://doi.org/10.1038/ni.2030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21516110"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21516110"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Lauren W Collison, Greg M Delgoffe, Clifford S Guy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The composition and signaling of the IL-35 receptor are unconventional."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.2227"}], "href": "https://doi.org/10.1038/ni.2227"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22306691"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22306691"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Anju T Peters, Atsushi Kato, Ning Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2009.10.072"}], "href": "https://doi.org/10.1016/j.jaci.2009.10.072"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20159251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20159251"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Ryan B Corcoran, Gianmarco Contino, Vikram Deshpande, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-11-0908"}], "href": "https://doi.org/10.1158/0008-5472.CAN-11-0908"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21586612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21586612"}]}]}]}
Synonyms	IL-6RB, CDW130, CD130, GP130
Proteins	IL6RB_HUMAN
NCBI Gene ID	3572
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

IL6ST has 15,440 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 142 datasets.

Click the + buttons to view associations for IL6ST from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

IL6ST Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of IL6ST gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of IL6ST gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of IL6ST gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of IL6ST gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of IL6ST gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of IL6ST gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of IL6ST gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of IL6ST gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of IL6ST gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of IL6ST gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of IL6ST gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of IL6ST gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with IL6ST gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with IL6ST protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with IL6ST gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of IL6ST gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of IL6ST gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of IL6ST gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with IL6ST gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of IL6ST gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing IL6ST protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of IL6ST gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing IL6ST protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing IL6ST protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing IL6ST protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing IL6ST protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with IL6ST protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with IL6ST protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing IL6ST protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of IL6ST gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with IL6ST gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with IL6ST gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with IL6ST gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of IL6ST protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by IL6ST gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate IL6ST protein from the curated DEPOD Substrates of Phosphatases dataset.
	DGIdb Drug Targets 2026	interacting drugs for IL6ST protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving IL6ST gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving IL6ST gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with IL6ST gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.