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Protein / target

Interleukin-6 receptor subunit beta

Encoded byIL6STP40189Homo sapiensSwiss-Prot
UniProt: P40189Ensembl: ENSG00000134352HGNC: HGNC:6021NCBI Gene: 3572
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
14
Clinical trials
Small-molecule tractable
Druggability
High-Quality Pocket

Protein at a glance

Biological role

Ciliary neurotrophic factor receptor

Strongest disease association

Neuromyelitis Optica

Via encoding gene IL6ST · Clinical evidence · score 0.57

Therapeutic position

Established drug target

Antibodies

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 overview

Functions as a shared signal-transducing subunit not only for IL6 but also for other cytokine receptor complexes, including IL6, LIF, OSM, CNTF, IL11, CTF1, BSF3, MT-RNR2/humanin, CLCF1 and the heterodimeric complex CRLF1-CLCF1.

View complete UniProt function annotation

Functions as a shared signal-transducing subunit not only for IL6 but also for other cytokine receptor complexes, including IL6, LIF, OSM, CNTF, IL11, CTF1, BSF3, MT-RNR2/humanin, CLCF1 and the heterodimeric complex CRLF1-CLCF1 (PubMed:11285233, PubMed:11294841, PubMed:1542794, PubMed:19386761, PubMed:2261637, PubMed:27384491, PubMed:36930708, PubMed:39532904, PubMed:8272873, PubMed:8999038, PubMed:9030543, PubMed:9188471). Engages site 2 of CNTF, CLCF1, LIF, and IL-6, and site 3 of IL27 and IL6 (PubMed:36930708). Initiates signal transmission through three mechanisms (PubMed:11285233, PubMed:11294841, PubMed:1542794, PubMed:19386761, PubMed:19915009, PubMed:2261637, PubMed:23294003). Binding of cytokines, such as IL6 or IL11 to the alpha-chains of their specific cell surface receptor triggers homodimerization of IL6ST/gp130 (PubMed:19915009, PubMed:2261637, PubMed:23294003, PubMed:8637716). In contrast, binding of other IL-6 family cytokines can result in the formation of a IL6ST/gp130 heterodimer with another signal-transducing receptor, such as LIFR or OSMR (PubMed:1542794, PubMed:39532904, PubMed:8999038, PubMed:9030543, PubMed:9188471). Moreover, binding of CNTF or CLCF1 or the heterodimeric complex CRLF1-CLCF1 or MT-RNR2/humanin to the non-signaling receptor CNTFR induces heterodimerization of the IL6ST/gp130 with LIFR or IL27RA/WSX1 (in the case of MT-RNR2/humanin) (PubMed:11285233, PubMed:11294841, PubMed:19386761). Mechanistically, homodimerization or heterodimerization of IL6ST/gp130 activate JAK tyrosine kinases bound to their intracellular domains (PubMed:11294841, PubMed:19915009, PubMed:2261637, PubMed:23294003, PubMed:27384491, PubMed:8272873, PubMed:9030543, PubMed:9188471). These kinases subsequently phosphorylate the homodimer or heterodimer form of IL6ST/gp130 (PubMed:11285233, PubMed:11294841, PubMed:19915009, PubMed:23294003, PubMed:25731159, PubMed:9030543). The tyrosine phosphorylated signaling receptors serve in turn as docking sites for recruitment and activation of signal transducer and activators of transcription (STATs) (PubMed:11285233, PubMed:11294841, PubMed:19386761, PubMed:19915009, PubMed:23294003, PubMed:25731159, PubMed:27384491, PubMed:9030543, PubMed:9188471). The IL6 signaling pathway induces, in parallel, the expression of two cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit JAK and terminate the activity of the IL6 signaling pathway as a negative feedback loop (By similarity). Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3 (By similarity). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (By similarity). Has a role in embryonic development (By similarity). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (By similarity). Required for expression of TRPA1 in nociceptive neurons (By similarity). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (By similarity). Required for normal trabecular bone mass and cortical bone composition (By similarity)

Subcellular location

Cell membraneSecreted
Domains and Gene Ontology detail (67)

Domains & features

Ig-like C2-typeFibronectin type-III 1Fibronectin type-III 2Fibronectin type-III 3Fibronectin type-III 4Fibronectin type-III 5

Gene Ontology

  • Cciliary neurotrophic factor receptor complex
  • Cdendrite
  • Cexternal side of plasma membrane
  • Cextracellular exosome
  • Cextracellular region
  • Cextracellular space
  • Cinterleukin-6 receptor complex
  • Cmembrane
  • Cmembrane raft
  • Cneuronal cell body
  • Concostatin-M receptor complex
  • Cplasma membrane

918 aa · 104 kDa · 3 isoforms

Biological roles

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

Cell proliferation & survivalGOImmune signallingUniProt · GOApoptosis & cell deathGO
View supporting evidence

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

Immune signalling

  • ·Functions as a shared signal-transducing subunit not only for IL6 but also for other cyt…
  • ·interleukin-6 receptor complex
  • ·cytokine binding
  • ·cytokine receptor activity

Apoptosis & cell death

  • ·negative regulation of apoptotic process
  • ·negative regulation of neuron apoptotic process

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

Approved medicines with mapped indications

1 medicine · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Immune System Diseases1 medicine
satralizumab
Neuromyelitis Optica1 medicine
satralizumab

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

satralizumab
ApprovedAntagonist

IL6Ralpha/GP130 antagonist

Indicated for Immune System Diseases, Neuromyelitis Optica

Acts on a complex — shared with IL6R · 1 of 2 recorded protein targets — narrow recorded profile

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

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene IL6ST

Gene-level evidence surfaced through the gene IL6ST that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Neuromyelitis Optica
0.70Moderately supported

Clinical evidence dominant · Open Targets 0.57

Immune System Diseases
0.47Limited support

Clinical evidence dominant · Open Targets 0.38

Adenoma, Liver Cell
0.41Limited support

Somatic mutation evidence dominant · Open Targets 0.37

View evidence synthesis (3)
Neuromyelitis OpticaModerately supported
0.70
agreement 0.55–0.86
Clinical100%Literature0%

Open Targets aggregate 0.57 · 2 independent evidence families

Immune System DiseasesLimited support
0.47
agreement 0.32–0.63
Clinical94%Literature6%

Open Targets aggregate 0.38 · 2 independent evidence families

Adenoma, Liver CellLimited support
0.41
agreement 0.25–0.57
Somatic mutation95%Literature5%

Open Targets aggregate 0.37 · 2 independent evidence families

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 per-type scores above show the calculation.

Show all associations
Neuromyelitis Optica0.57
Immune System Diseases0.38
Adenoma, Liver Cell0.37

Drug development

1 compounds recorded · 1 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (1)
SATRALIZUMABApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Emerging

Feasibility evidence (high-quality pocket) — no clinical-stage drug of this modality recorded.

Antibodies — Strong

Approved Drug and UniProt loc high conf support this modality.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · High-Quality PocketAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

14

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

A Comparative Clinical Effectiveness Trial of Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab and Eculizumab To Prevent Relapses in Neuromyelitis Optica Spectrum DisorderPHASE4

NOT_YET_RECRUITING · via satralizumab · NCT07010302

A Phase III, Multicenter, Open-Label, Uncontrolled Study To Evaluate Pharmacokinetics, Efficacy, Safety, Tolerability, And Pharmacodynamics Of Satralizumab In Pediatric Patients With AQP4 Antibody Positive Neuromyelitis Optica Spectrum Disorder (NMOSD)PHASE3

RECRUITING · via satralizumab · NCT05199688

A Phase III, Randomized, Double-Masked, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Participants With Moderate-to-Severe Thyroid Eye DiseasePHASE3

ACTIVE_NOT_RECRUITING · via satralizumab · NCT06106828

A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Basket Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Patients With Anti-N-methyl-D-aspartic Acid Receptor (NMDAR) or Anti-leucine-rich Glioma-inactivated 1 (LGI1) EncephalitisPHASE3

ACTIVE_NOT_RECRUITING · via satralizumab · NCT05503264

View all trials (10)
A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab as Monotherapy or in Addition to Baseline Therapy in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (MOGAD)PHASE3

ACTIVE_NOT_RECRUITING · via satralizumab · NCT05271409

A Phase II Multicenter, Open-label Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Pediatric Patients With Duchenne Muscular Dystrophy (SHIELD DMD)PHASE2

ACTIVE_NOT_RECRUITING · via satralizumab · NCT06450639

SAkuraBonsai: Clinical, Imaging And Biomarker Open-Label Study In Neuromyelitis Optica Spectrum Disorder (NMOSD) With Satralizumab As An InterventionPHASE4

TERMINATED · via satralizumab · NCT05269667

A Phase III, Randomized, Double-Masked, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Participants With Moderate-to-Severe Thyroid Eye DiseasePHASE3

COMPLETED · via satralizumab · NCT05987423

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate Efficacy, Safety, Pharmacokinetics, And Pharmacodynamics Of Satralizumab In Patients With Generalized Myasthenia GravisPHASE3

TERMINATED · via satralizumab · NCT04963270

A Multicenter, Single Arm, Open-Label Study to Evaluate the Long-Term Safety and Efficacy of Satralizumab in Patients With Neuromyelitis Optica Spectrum Disorder (NMOSD)PHASE3

COMPLETED · via satralizumab · NCT04660539

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) as Monotherapy in Patients With Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD)PHASE3

COMPLETED · via satralizumab · NCT02073279

A Multicenter, Randomized, Addition to Baseline Treatment, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) in Patients With Neuromyelitis Optica (NMO) and NMO Spectrum Disorder (NMOSD)PHASE3

COMPLETED · via satralizumab · NCT02028884

Satralizumab,an Anti-IL-6 Receptor Antibody, in the Treatment of Pulmonary Arterial Hypertension; Safety and Efficacy Evaluation in Japan -Multicenter, Investigator-sponsored Trial-PHASE2

COMPLETED · via satralizumab · NCT05679570

A Phase 1 Clinical Trial of Satralizumab as a Treatment for Aneurysmal Subarachnoid HemorrhageEARLY_PHASE1

WITHDRAWN · via satralizumab · NCT05727657

ClinicalTrials.gov via the drug-target graph.

What's happening now

8

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Trial results posted2026-07-31

    A Phase III, Randomized, Double-Masked, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Participants With Moderate-to-Severe Thyroid Eye Disease

    Results posted · ClinicalTrials.gov · via satralizumab

  2. Trial status changed2026-07-31

    A Phase III, Randomized, Double-Masked, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Participants With Moderate-to-Severe Thyroid Eye Disease

    Status changed to Completed · ClinicalTrials.gov · via satralizumab

  3. Trial status changed2026-07-15

    Satralizumab,an Anti-IL-6 Receptor Antibody, in the Treatment of Pulmonary Arterial Hypertension; Safety and Efficacy Evaluation in Japan -Multicenter, Investigator-sponsored Trial-

    Status changed to Completed · ClinicalTrials.gov · via satralizumab

  4. Supplemental approval2026-06-10

    Supplemental approval: SATRALIZUMAB (BLA761149)

    fda · regulatory · fda · via satralizumab

  5. Label change2022-09-14

    Label change: SATRALIZUMAB (BLA761149)

    fda · regulatory · fda · via satralizumab

  6. Regulatory approval2021-06-24

    Approval: Enspryng (EMA)

    ema · regulatory · ema · via satralizumab

  7. Label change2021-05-03

    Label change: SATRALIZUMAB (BLA761149)

    fda · regulatory · fda · via satralizumab

  8. Regulatory approval2020-08-14

    Approval: SATRALIZUMAB (BLA761149)

    fda · regulatory · fda · via satralizumab

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.