Protein / target
Interleukin-6 receptor subunit alpha
Protein at a glance
Biological role
Ciliary neurotrophic factor binding
Primary system
Immune system
Strongest disease association
coronary artery disorder
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
4 approved · 1 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to the regulation of the immune response, acute-phase reactions and hematopoiesis (PubMed:30995492, PubMed:31235509). The interaction with membrane-bound IL6R and IL6ST stimulates 'classic signaling', the restricted expression of the IL6R limits classic IL6 signaling to only a few tissues such as the liver and some cells of the immune system. Whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable)
Subcellular location
Domains and Gene Ontology detail (47)Hide
Domains & features
Gene Ontology
- Capical plasma membrane
- Cciliary neurotrophic factor receptor complex
- Cexternal side of plasma membrane
- Cextracellular region
- Cextracellular space
- Cinterleukin-6 receptor complex
- Cplasma membrane
- Creceptor complex
- Fciliary neurotrophic factor binding
- Fcytokine receptor activity
- Fenzyme binding
- Finterleukin-11 binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Immune signalling
- ·Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not tra…
- ·interleukin-6 receptor complex
- ·cytokine receptor activity
- ·interleukin-11 binding
Transcriptional regulation
- ·Transcriptional regulation of granulopoiesis
View underlying pathways (7)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Interleukin-6 receptor alpha subunit inhibitor
Appears in clinical studies involving temporal arteritis, juvenile idiopathic arthritis, rheumatoid arthritis, systemic sclerosis
Interleukin-6 receptor alpha subunit antagonist
Appears in clinical studies involving rheumatoid arthritis, immune system disorder, ankylosing spondylitis, COVID-19
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,042 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 5 total
neuromyelitis optica · neuromyelitis optica · immune system disorder
temporal arteritis · juvenile idiopathic arthritis · rheumatoid arthritis
immune system disorder · rheumatoid arthritis · COVID-19
rheumatoid arthritis · immune system disorder · ankylosing spondylitis
rheumatoid arthritis · systemic lupus erythematosus
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Regulatory approval
Approval: Tuyory (EMA)
- Regulatory approval
Approval: Avtozma (EMA)
- Regulatory approval
Approval: Tocilizumab STADA (previously Tofidence) (EMA)
- Regulatory approval
Approval: Tyenne (EMA)
- New publicationSubcutaneous sarilumab for the treatment of hospitalized patients with moderate to severe COVID19 disease: A pragmatic, embedded randomized clinical trial.
- New publicationSarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial.
- New publicationAssociation Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis.
- New publicationInterleukin-6 blockade with tocilizumab increases Tregs and reduces T effector cytokines in renal graft inflammation: A randomized controlled trial.
- New publicationEffect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial.
- New publicationImmunopathogenesis and treatment of cytokine storm in COVID-19.
- New publicationCOVIDOSE: A Phase II Clinical Trial of Low-Dose Tocilizumab in the Treatment of Noncritical COVID-19 Pneumonia.
- New publicationCytokine Storm in COVID-19: The Current Evidence and Treatment Strategies.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.