Protein / target

Interleukin-6

IL6P05231Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
9
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

Interleukin-6 receptor binding

Primary system

Immune system

Strongest disease association

asthma

Genetic evidence · score 0.86

Therapeutic maturity

Clinically validated target

3 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Structure with Ligand

Clinical development

3 approved · 3 in clinical development

9 linked trials

Research activity

Actively researched

65 papers · latest 2024

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

Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', 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

Secreted
Domains and Gene Ontology detail (102)

Gene Ontology

  • Cendoplasmic reticulum lumen
  • Cextracellular region
  • Cextracellular space
  • Cinterleukin-6 receptor complex
  • Cplasma membrane
  • Fcytokine activity
  • Fgrowth factor activity
  • Fidentical protein binding
  • Finterleukin-6 receptor binding
  • Pacute-phase response
  • Pautocrine signaling
  • Pcell surface receptor signaling pathway via JAK-STAT

212 aa · 24 kDa

Biological roles

Reactome v97

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

Immune signallingUniProt · GO · ReactomeTranscriptional regulationGO · ReactomeKinase signallingGO · ReactomeApoptosis & cell deathGOHaemostasisGOCell adhesionGO
View supporting evidence

Immune signalling

  • ·Cytokine with a wide variety of biological functions in immunity, tissue regeneration, a…
  • ·interleukin-6 receptor complex
  • ·cytokine activity
  • ·interleukin-6 receptor binding

Transcriptional regulation

  • ·positive regulation of DNA-templated transcription
  • ·positive regulation of gene expression
  • ·positive regulation of miRNA transcription
  • ·positive regulation of transcription by RNA polymerase II

Kinase signalling

  • ·positive regulation of peptidyl-serine phosphorylation
  • ·positive regulation of peptidyl-tyrosine phosphorylation
  • ·Post-translational protein phosphorylation

Apoptosis & cell death

  • ·negative regulation of apoptotic process
  • ·neutrophil apoptotic process
  • ·positive regulation of apoptotic process
  • ·positive regulation of type B pancreatic cell apoptotic process

Haemostasis

  • ·platelet activation
  • ·positive regulation of platelet aggregation

Cell adhesion

  • ·positive regulation of extracellular matrix disassembly
View underlying pathways (13)

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.

IL6RIL2IL6STIL3IL1R1TNFRSF…IL10IL1BJAK1JAK2IL6

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

1

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.

ziltivekimab
Narrow target profilePhase 3Inhibitor

Interleukin-6 inhibitor

Appears in clinical studies involving heart failure, atherosclerosis, coronary artery disorder, acute myocardial infarction

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.

asthma0.86

Genetic · overall 0.56

aortic stenosis0.82

Genetic · overall 0.51

aortic valve calcification0.76

Genetic · overall 0.46

atrial fibrillation0.67

Genetic · overall 0.43

atherosclerosis0.64

Genetic · overall 0.47

Highest-confidence therapeutic associations

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

immune system disorder0.83

Clinical · overall 0.51

Giant Lymph Node Hyperplasia0.76

Clinical · overall 0.46

rheumatoid arthritis0.67

Clinical · overall 0.52

COVID-190.56

Clinical · overall 0.44

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

Kaposi sarcoma, susceptibility to0.46

Genetic literature

Show all associations
asthma0.56
rheumatoid arthritis0.52
immune system disorder0.51
aortic stenosis0.51
atherosclerosis0.47
aortic valve calcification0.46
Giant Lymph Node Hyperplasia0.46
Kaposi sarcoma, susceptibility to0.46
COVID-190.44
atrial fibrillation0.43

Open Targets ranks 3,888 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 · 6 total

SILTUXIMABApproval

Giant Lymph Node Hyperplasia · idiopathic multicentric Castleman disease · anemia

OLOKIZUMABApproval

immune system disorder · rheumatoid arthritis · interstitial lung disease

ZILTIVEKIMABPhase 3

heart failure · atherosclerosis · coronary artery disorder

CLAZAKIZUMABPhase 3

diabetes mellitus · Crohn disease · rheumatoid arthritis

SIRUKUMABApproval

immune system disorder · cutaneous lupus erythematosus · temporal arteritis

PACIBEKITUGPhase 2

Crohn disease · systemic lupus erythematosus · Crohn disease

Tractability

SM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule Binder

Safety liabilities

regulation of transcription factor activityregulation of gene expressiondepression

Clinical trials

9

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

ClinicalTrials.gov via the drug-target graph.

Research activity

65 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Tanaka T · Cold Spring Harbor perspectives in biology · 2014

Heinrich PC · The Biochemical journal · 1990

Smith SE · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007

Landskron G · Journal of immunology research · 2014

Recent

Europe PMC papers linked directly to this protein.

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.

asthmaWell supported
0.89
agreement 0.781.00
Genetic77%Literature13%Clinical10%

Open Targets aggregate 0.56 · 3 independent evidence families

aortic stenosisWell supported
0.82
agreement 0.690.96
Genetic95%Literature5%

Open Targets aggregate 0.51 · 2 independent evidence families

atherosclerosisWell supported
0.79
agreement 0.690.90
Genetic58%Clinical31%Literature11%

Open Targets aggregate 0.47 · 3 independent evidence families

rheumatoid arthritisWell supported
0.78
agreement 0.670.90
Clinical44%Genetic literature43%Literature13%

Open Targets aggregate 0.52 · 3 independent evidence families

COVID-19Well supported
0.77
agreement 0.660.88
Genetic48%Clinical38%Literature14%

Open Targets aggregate 0.44 · 3 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

1

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2021-05-17
    Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease.

    Circulation research · 2021 · 459 citations · Europe PMC · via ziltivekimab

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.