Protein / target

Interleukin-6 receptor subunit alpha

IL6RP08887Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
4
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

Ciliary neurotrophic factor binding

Primary system

Immune system

Strongest disease association

coronary artery disorder

Genetic evidence · score 0.91

Therapeutic maturity

Clinically validated target

4 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Structure with Ligand

Clinical development

4 approved · 1 in clinical development

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

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

Cell membraneSecreted
Domains and Gene Ontology detail (47)

Domains & features

Ig-like C2-typeFibronectin type-III 1Fibronectin type-III 2

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

468 aa · 52 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Immune signallingUniProt · GO · ReactomeTranscriptional regulationReactome
View supporting evidence

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)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

IL6STIL6IL11STAT3JAK1TNFCNTFIL1BJAK2TYK2IL6R

10 strongest partners — larger node and heavier line mean higher confidence

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

2

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.

tocilizumab
Narrow target profileApprovedInhibitor

Interleukin-6 receptor alpha subunit inhibitor

Appears in clinical studies involving temporal arteritis, juvenile idiopathic arthritis, rheumatoid arthritis, systemic sclerosis

Direct interaction with this protein · Only this protein recorded as a target

sarilumab
Narrow target profileApprovedAntagonist

Interleukin-6 receptor alpha subunit antagonist

Appears in clinical studies involving rheumatoid arthritis, immune system disorder, ankylosing spondylitis, COVID-19

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

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.

coronary artery disorder0.91

Genetic · overall 0.58

atopic eczema0.90

Genetic · overall 0.55

asthma0.88

Genetic · overall 0.56

Eczematoid dermatitis0.86

Genetic · overall 0.64

rheumatoid arthritis0.82

Genetic · overall 0.74

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

juvenile idiopathic arthritis0.95

Clinical · overall 0.60

temporal arteritis0.94

Clinical · overall 0.58

neuromyelitis optica0.94

Clinical · overall 0.58

COVID-190.91

Clinical · overall 0.63

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

hyper-IgE recurrent infection syndrome 5, autosomal recessive0.58

Genetic

Show all associations
rheumatoid arthritis0.74
Eczematoid dermatitis0.64
COVID-190.63
juvenile idiopathic arthritis0.60
neuromyelitis optica0.58
coronary artery disorder0.58
temporal arteritis0.58
hyper-IgE recurrent infection syndrome 5, autosomal recessive0.58
asthma0.56
atopic eczema0.55

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

SATRALIZUMABApproval

neuromyelitis optica · neuromyelitis optica · immune system disorder

TOCILIZUMABApproval

temporal arteritis · juvenile idiopathic arthritis · rheumatoid arthritis

LEVILIMABApproval

immune system disorder · rheumatoid arthritis · COVID-19

SARILUMABApproval

rheumatoid arthritis · immune system disorder · ankylosing spondylitis

VOBARILIZUMABPhase 2

rheumatoid arthritis · systemic lupus erythematosus

Tractability

SM · Structure with LigandAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMM

Safety liabilities

regulation of transcription factor activity

Clinical trials

30

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)

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

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.

rheumatoid arthritisWell supported
0.96
agreement 0.851.00
Genetic49%Clinical44%Literature7%

Open Targets aggregate 0.74 · 3 independent evidence families

coronary artery disorderWell supported
0.92
agreement 0.811.00
Genetic87%Literature13%Clinical0%

Open Targets aggregate 0.58 · 3 independent evidence families

atopic eczemaWell supported
0.91
agreement 0.771.00
Genetic99%Literature1%

Open Targets aggregate 0.55 · 2 independent evidence families

asthmaWell supported
0.89
agreement 0.761.00
Genetic90%Literature10%

Open Targets aggregate 0.56 · 2 independent evidence families

Eczematoid dermatitisWell supported
0.87
agreement 0.731.00
Genetic97%Literature3%Genetic literaturedup

Open Targets aggregate 0.64 · 2 independent evidence families · 1 not counted as duplicate

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

23

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.

  1. Regulatory approval2026-04-27

    Approval: Tuyory (EMA)

    ema · regulatory · ema · via tocilizumab

  2. Regulatory approval2025-02-14

    Approval: Avtozma (EMA)

    ema · regulatory · ema · via tocilizumab

  3. Regulatory approval2024-06-20

    Approval: Tocilizumab STADA (previously Tofidence) (EMA)

    ema · regulatory · ema · via tocilizumab

  4. Regulatory approval2023-09-15

    Approval: Tyenne (EMA)

    ema · regulatory · ema · via tocilizumab

  5. New publication2022-02-25
    Subcutaneous sarilumab for the treatment of hospitalized patients with moderate to severe COVID19 disease: A pragmatic, embedded randomized clinical trial.

    PloS one · 2022 · 13 citations · Europe PMC · via sarilumab

  6. New publication2021-11-17
    Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial.

    The Lancet. Rheumatology · 2022 · 33 citations · Europe PMC · via sarilumab

  7. New publication2021-08-01
    Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis.

    JAMA · 2021 · 548 citations · Europe PMC · via tocilizumab

  8. New publication2021-01-21
    Interleukin-6 blockade with tocilizumab increases Tregs and reduces T effector cytokines in renal graft inflammation: A randomized controlled trial.

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021 · 53 citations · Europe PMC · via tocilizumab

  9. New publication2021-01-01
    Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial.

    JAMA internal medicine · 2021 · 592 citations · Europe PMC · via tocilizumab

  10. New publication2021-01-01
    Immunopathogenesis and treatment of cytokine storm in COVID-19.

    Theranostics · 2021 · 308 citations · Europe PMC · via tocilizumab

  11. New publication2020-12-10
    COVIDOSE: A Phase II Clinical Trial of Low-Dose Tocilizumab in the Treatment of Noncritical COVID-19 Pneumonia.

    Clinical pharmacology and therapeutics · 2021 · 45 citations · Europe PMC · via tocilizumab

  12. New publication2020-07-10
    Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies.

    Frontiers in immunology · 2020 · 756 citations · Europe PMC · via tocilizumab

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.