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IL6ST interleukin 6 signal transducer [ Homo sapiens (human) ]

Gene ID: 3572, updated on 24-Nov-2020

Summary

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Official Symbol
IL6STprovided by HGNC
Official Full Name
interleukin 6 signal transducerprovided by HGNC
Primary source
HGNC:HGNC:6021
See related
Ensembl:ENSG00000134352 MIM:600694
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CD130; GP130; HIES4; CDW130; IL-6RB; sGP130
Summary
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]
Annotation information
Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
Expression
Ubiquitous expression in placenta (RPKM 88.6), fat (RPKM 53.5) and 24 other tissues See more
Orthologs
mouse all

Genomic context

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See IL6ST in Genome Data Viewer
Location:
5q11.2
Exon count:
19
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 5 NC_000005.10 (55935095..55994963, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (55230923..55290821, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene heterogeneous nuclear ribonucleoprotein H1 pseudogene 3 Neighboring gene interleukin 31 receptor A Neighboring gene Sharpr-MPRA regulatory region 5314 Neighboring gene uncharacterized LOC441072 Neighboring gene uncharacterized LOC105378976 Neighboring gene ankyrin repeat domain 55

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Glycoprotein-130 Expression Is Associated with Aggressive Bladder Cancer and Is a Potential Therapeutic Target. Martin DT, et al. Mol Cancer Ther, 2019 Feb. PMID 30381445, Free PMC Article
  2. Selective loss of function variants in IL6ST cause Hyper-IgE syndrome with distinct impairments of T-cell phenotype and function. Shahin T, et al. Haematologica, 2019 Mar. PMID 30309848, Free PMC Article
  3. Soluble glycoprotein 130 is inversely related to severity of coronary atherosclerosis. Korotaeva AA, et al. Biomarkers, 2018 Sep. PMID 29580104
  4. Circulating levels of sgp130 and sex hormones in male patients with coronary atherosclerotic disease. Cui Y, et al. Atherosclerosis, 2017 Nov. PMID 29028483
  5. Association of IL6ST (gp130) Polymorphism with Functional Outcome Following Spontaneous Intracerebral Hemorrhage. El Husseini N, et al. J Stroke Cerebrovasc Dis, 2018 Jan. PMID 28964648

See all (268) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Physical proximity and functional cooperation of glycoprotein 130 and glycoprotein VI in platelet membrane lipid rafts.
    Title: Physical proximity and functional cooperation of glycoprotein 130 and glycoprotein VI in platelet membrane lipid rafts.
  2. our data suggest that characteristic features of GP130-deficient hyper-IgE syndrome phenotype are IL-6 and IL-11 dominated, and indicate selective roles of aberrant IL-6 and IL-27 signaling on the differentiation of T-cell subsets.
    Title: Selective loss of function variants in <i>IL6ST</i> cause Hyper-IgE syndrome with distinct impairments of T-cell phenotype and function.
  3. IL-6 variants with different affinities to gp130 showed a range of signaling amplitudes and induced biased signaling, with changes in receptor binding dwell-times affecting more profoundly STAT1 than STAT3 phosphorylation.
    Title: Kinetics of cytokine receptor trafficking determine signaling and functional selectivity.
  4. our findings demonstrate that defective glycosylation in PGM3-deficient patients results in reduced expression of unglycosylated gp130 protein and consequently, impaired gp130-dependent STAT3 phosphorylation.
    Title: Defective glycosylation leads to defective gp130-dependent STAT3 signaling in PGM3-deficient patients.
  5. Results found that GP130 is expressed in the aggressive human bladder tumors and in high-grade bladder cancer cell lines. Moreover, GP130 is significantly correlated with tumor grade, node category, tumor category, and patient outcome.
    Title: Glycoprotein-130 Expression Is Associated with Aggressive Bladder Cancer and Is a Potential Therapeutic Target.
  6. Ectopic upregulation of membrane-bound IL6R drives vascular remodeling in pulmonary arterial hypertension.
    Title: Ectopic upregulation of membrane-bound IL6R drives vascular remodeling in pulmonary arterial hypertension.
  7. Low plasma IL6ST level is associated with poor response to sunitinib in metastatic clear cell renal cell carcinoma.
    Title: Elevated plasma interleukin 6 predicts poor response in patients treated with sunitinib for metastatic clear cell renal cell carcinoma.
  8. Multiple MSI2-regulated mRNAs have been identified, and evidence has been provided that MSI2 controls IL6ST activity that control oncogenic signaling networks.
    Title: Transcriptome-wide analysis uncovers the targets of the RNA-binding protein MSI2 and effects of MSI2's RNA-binding activity on IL-6 signaling.
  9. Blocking the interaction between IL-6 and GP130 may inhibit the IL-6/GP130/STAT3 signaling pathway.
    Title: Bazedoxifene exhibits growth suppressive activity by targeting interleukin-6/glycoprotein 130/signal transducer and activator of transcription 3 signaling in hepatocellular carcinoma.
  10. findings indicate that even though high concentrations of sIL-6R and sgp130 are present in human serum, the relative ratio of free IL-6 to IL-6.sIL-6R allows for simultaneous classic and trans-signaling
    Title: The balance of interleukin (IL)-6, IL-6·soluble IL-6 receptor (sIL-6R), and IL-6·sIL-6R·sgp130 complexes allows simultaneous classic and trans-signaling.
Submit: New GeneRIF Correction See all GeneRIFs (169)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
GeneReviews: Not available
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
GeneReviews: Not available
HYPER-IgE RECURRENT INFECTION SYNDROME 4, AUTOSOMAL RECESSIVE
MedGen: C5193141 OMIM: 618523 GeneReviews: Not available
not available
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of interleukin 6 signal transducer (IL6ST; gp130, oncostatin M receptor; CD130) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Nef nef HIV-1 Nef downregulates the cell surface expression of interleukin 6 signal transducer (IL6ST, CD130) PubMed
Tat tat HIV-1 Tat upregulates the expression of interleukin 6 signal transducer gene (IL6ST; GP130) in mammary epithelial cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • DKFZp564F053

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ciliary neurotrophic factor receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
ciliary neurotrophic factor receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
cytokine binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
cytokine receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
growth factor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
contributes_to growth factor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
interleukin-11 binding IEA
Inferred from Electronic Annotation
more info
  
interleukin-11 receptor activity IEA
Inferred from Electronic Annotation
more info
  
interleukin-27 receptor activity IC
Inferred by Curator
more info
 PubMed 
contributes_to interleukin-6 binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
contributes_to interleukin-6 binding IPI
Inferred from Physical Interaction
more info
 PubMed 
contributes_to interleukin-6 receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
contributes_to interleukin-6 receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
contributes_to interleukin-6 receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
contributes_to leukemia inhibitory factor receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
contributes_to oncostatin-M receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
ciliary neurotrophic factor-mediated signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
cytokine-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
cytokine-mediated signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
  
glycogen metabolic process IEA
Inferred from Electronic Annotation
more info
  
interleukin-11-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
  
interleukin-27-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
interleukin-27-mediated signaling pathway TAS
Traceable Author Statement
more info
  
interleukin-35-mediated signaling pathway TAS
Traceable Author Statement
more info
  
interleukin-6-mediated signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
interleukin-6-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
interleukin-6-mediated signaling pathway TAS
Traceable Author Statement
more info
  
intestinal epithelial cell development IDA
Inferred from Direct Assay
more info
 PubMed 
leukemia inhibitory factor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
negative regulation of apoptotic process TAS
Traceable Author Statement
more info
 PubMed 
oncostatin-M-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
positive regulation of Notch signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
positive regulation of T cell proliferation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
positive regulation of acute inflammatory response IC
Inferred by Curator
more info
 PubMed 
positive regulation of adaptive immune response IC
Inferred by Curator
more info
 PubMed 
positive regulation of astrocyte differentiation IEA
Inferred from Electronic Annotation
more info
  
positive regulation of cardiac muscle hypertrophy TAS
Traceable Author Statement
more info
 PubMed 
positive regulation of cell population proliferation IDA
Inferred from Direct Assay
more info
 PubMed 
positive regulation of cell population proliferation IGI
Inferred from Genetic Interaction
more info
 PubMed 
positive regulation of osteoblast differentiation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
positive regulation of tyrosine phosphorylation of STAT protein IMP
Inferred from Mutant Phenotype
more info
 PubMed 
positive regulation of vascular endothelial growth factor production TAS
Traceable Author Statement
more info
 PubMed 
response to cytokine IDA
Inferred from Direct Assay
more info
 PubMed 
viral process IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
ciliary neurotrophic factor receptor complex IDA
Inferred from Direct Assay
more info
 PubMed 
external side of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
extracellular exosome HDA PubMed 
extracellular region TAS
Traceable Author Statement
more info
  
interleukin-6 receptor complex IDA
Inferred from Direct Assay
more info
 PubMed 
membrane HDA PubMed 
neuronal cell body IEA
Inferred from Electronic Annotation
more info
  
oncostatin-M receptor complex IDA
Inferred from Direct Assay
more info
 PubMed 
plasma membrane TAS
Traceable Author Statement
more info
  
receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 

General protein information

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Preferred Names
interleukin-6 receptor subunit beta
Names
CD130 antigen
IL-6 receptor subunit beta
IL-6R subunit beta
gp130 of the rheumatoid arthritis antigenic peptide-bearing soluble form
gp130, oncostatin M receptor
interleukin receptor beta chain
membrane glycoprotein 130
membrane glycoprotein gp130
oncostatin-M receptor subunit alpha

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001190981.2 → NP_001177910.1  interleukin-6 receptor subunit beta isoform 3 precursor

    See identical proteins and their annotated locations for NP_001177910.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (3) that is shorter than isoform 1.
    Source sequence(s)
    AB102802, AC008914, AC016596, BQ013034, DA863210, DA877322
    Consensus CDS
    CCDS54856.1
    UniProtKB/Swiss-Prot
    P40189
    UniProtKB/TrEMBL
    A0A0A0N0L2
    Related
    ENSP00000370694.3, ENST00000381294.7
    Conserved Domains (4) summary
    smart00060
    Location:458 → 538
    FN3; Fibronectin type 3 domain
    cd00063
    Location:222 → 321
    FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
    pfam06328
    Location:26 → 112
    Lep_receptor_Ig; Ig-like C2-type domain
    cl21522
    Location:121 → 215
    FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

  2. NM_001364275.2 → NP_001351204.1  interleukin-6 receptor subunit beta isoform 4 precursor

    Status: REVIEWED

    Source sequence(s)
    AC008914, AC016596, HQ628629
    Conserved Domains (4) summary
    smart00060
    Location:485 → 565
    FN3; Fibronectin type 3 domain
    cd00063
    Location:222 → 321
    FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
    pfam06328
    Location:26 → 112
    Lep_receptor_Ig; Ig-like C2-type domain
    cl21522
    Location:121 → 215
    FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

  3. NM_001364276.2 → NP_001351205.1  interleukin-6 receptor subunit beta isoform 5 precursor

    Status: REVIEWED

    Source sequence(s)
    AC008914, AC016596
    Conserved Domains (4) summary
    smart00060
    Location:449 → 529
    FN3; Fibronectin type 3 domain
    cd00063
    Location:152 → 251
    FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
    pfam06328
    Location:26 → 53
    Lep_receptor_Ig; Ig-like C2-type domain
    cl21522
    Location:54 → 145
    FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

  4. NM_001364277.2 → NP_001351206.1  interleukin-6 receptor subunit beta isoform 6

    Status: REVIEWED

    Source sequence(s)
    AC008914, AC016596
    Conserved Domains (1) summary
    smart00060
    Location:230 → 310
    FN3; Fibronectin type 3 domain

  5. NM_001364278.2 → NP_001351207.1  interleukin-6 receptor subunit beta isoform 7

    Status: REVIEWED

    Source sequence(s)
    AC008914, AC016596
    Conserved Domains (1) summary
    smart00060
    Location:218 → 298
    FN3; Fibronectin type 3 domain

  6. NM_001364279.2 → NP_001351208.1  interleukin-6 receptor subunit beta isoform 8

    Status: REVIEWED

    Source sequence(s)
    AC008914, AC016596
    Conserved Domains (1) summary
    smart00060
    Location:187 → 267
    FN3; Fibronectin type 3 domain

  7. NM_002184.4 → NP_002175.2  interleukin-6 receptor subunit beta isoform 1 precursor

    See identical proteins and their annotated locations for NP_002175.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC008914, AC016596, BC117402, BQ013034, DA863210, M57230
    Consensus CDS
    CCDS3971.1
    UniProtKB/Swiss-Prot
    P40189
    UniProtKB/TrEMBL
    Q17RA0
    Related
    ENSP00000370698.2, ENST00000381298.7
    Conserved Domains (4) summary
    smart00060
    Location:519 → 599
    FN3; Fibronectin type 3 domain
    cd00063
    Location:222 → 321
    FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
    pfam06328
    Location:26 → 112
    Lep_receptor_Ig; Ig-like C2-type domain
    cl21522
    Location:121 → 215
    FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

  8. NM_175767.3 → NP_786943.1  interleukin-6 receptor subunit beta isoform 2 precursor

    See identical proteins and their annotated locations for NP_786943.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate internal exon, which results in a frameshift in the 3' coding region and a premature termination codon, compared to variant 1. The resulting isoform (2, also known as gp130-RAPS) has a distinct and shorter C-terminus, compared to isoform 1.
    Source sequence(s)
    AB015706, AB102802, AC008914, AC016596, BQ013034, DA863210, DA877322
    Consensus CDS
    CCDS47209.1
    UniProtKB/Swiss-Prot
    P40189
    Related
    ENSP00000370687.4, ENST00000381287.8
    Conserved Domains (3) summary
    cd00063
    Location:222 → 321
    FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
    pfam06328
    Location:26 → 112
    Lep_receptor_Ig; Ig-like C2-type domain
    cl21522
    Location:121 → 215
    FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

RNA

  1. NR_120480.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) has an additional internal exon, compared to variant 1. This variant is represented as non-coding because use of the 5'-most expected translation start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC008914, AC016596, BC143842, BQ013034, DA863210, M57230

  2. NR_157112.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC008914, AC016596
    Related
    ENST00000651614.1

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p13 Primary Assembly

    Range
    55935095..55994963 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P40189.2 GenPept UniProtKB/Swiss-Prot:P40189

Gene LinkOut

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