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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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IL6
interleukin 6
Chromosome 7 · 7p15.3
NCBI Gene: 3569Ensembl: ENSG00000136244.12HGNC: HGNC:6018UniProt: B4DNQ5
5,468PubMed Papers
21Diseases
7Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly StudiedLandmark Gene
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of B cell activationregulation of insulin secretionpositive regulation of translationpositive regulation of smooth muscle cell proliferationasthmaaortic stenosisrheumatoid arthritisimmune system disease
✦AI Summary

IL6 is a multifunctional cytokine with critical roles across metabolic, vascular, and immune regulation. Functionally, IL6 acts as an essential regulator of bone homeostasis and angiogenesis through VEGF induction 12, and functions as a myokine released during muscle contraction to enhance lipolysis and improve insulin sensitivity 3. IL6 signals primarily through the IL6-GP130-STAT3 JAK2 pathway 45. The N-glycosylation status of IL6 determines downstream signaling preference: glycosylated IL6 sustains JAK-STAT3 signaling, while non-glycosylated IL6 shifts signaling toward the SRC-YAP-SOX2 axis, promoting epithelial-mesenchymal transition 5. In endothelial cells, IL6 mediates mesenchymal transition and organ fibrosis when autophagy is defective 6. IL6 is dysregulated across multiple diseases: elevated IL6 promotes brain metastasis in lung cancer via microglia polarization 4 and suppresses anti-tumor T and NK cell responses in EGFR-mutant NSCLC 7. Clinically, elevated IL6 and IL6R expression predict poor survival in colorectal cancer and associate with endometrial dysfunction in recurrent implantation failure 89. IL6 gene polymorphisms (rs1800795, rs1800796) correlate with neurological disorders including schizophrenia, Alzheimer's, and Parkinson's disease, with elevated IL6 expression associated with reduced brain cancer survival 10.

Sources cited
1
IL6 acts as essential factor in bone homeostasis and VEGF induction for angiogenesis
PMID: 12794819
2
IL6 induces VEGF and increases vascular permeability
PMID: 17075861
3
IL6 is discharged into bloodstream after muscle contraction, increasing lipolysis and improving insulin resistance
PMID: 20823453
4
Decreased IL6 in mid-secretory endometrium inhibits cell proliferation and decidualization in recurrent implantation failure
PMID: 34026283
5
IL6 induces anti-inflammatory microglia via JAK2/STAT3 signaling to promote brain metastasis in NSCLC
PMID: 35194016
6
IL6 suppresses T and NK cell function in EGFR-mutant NSCLC with acquired TKI resistance
PMID: 36595561
7
IL6 mediates endothelial-to-mesenchymal transition and organ fibrosis when endothelial autophagy is defective
PMID: 31965901
8
N-glycosylated IL6 sustains JAK-STAT3 signaling while non-glycosylated IL6 shifts signaling to SRC-YAP-SOX2 axis promoting EMT
PMID: 39251588
9
High IL6R expression in tumor epithelium and IL6 in tumor stroma predict poor survival in colorectal cancer
PMID: 39766336
10
IL6 SNPs associate with neurological disorders and elevated IL6 expression with decreased brain cancer survival
PMID: 39812719
Disease Associationsⓘ21
asthmaOpen Targets
0.58Moderate
aortic stenosisOpen Targets
0.53Moderate
rheumatoid arthritisOpen Targets
0.51Moderate
immune system diseaseOpen Targets
0.51Moderate
aortic valve calcificationOpen Targets
0.49Moderate
Kaposi's sarcomaOpen Targets
0.49Moderate
Giant Lymph Node HyperplasiaOpen Targets
0.47Moderate
Kaposi sarcoma, susceptibility toOpen Targets
0.46Moderate
atrial fibrillationOpen Targets
0.46Moderate
hair colorOpen Targets
0.45Moderate
aortic valve diseaseOpen Targets
0.44Moderate
COVID-19Open Targets
0.43Moderate
atherosclerosisOpen Targets
0.43Moderate
juvenile idiopathic arthritisOpen Targets
0.42Moderate
heart valve diseaseOpen Targets
0.41Moderate
abnormal chest soundsOpen Targets
0.41Moderate
atrial flutterOpen Targets
0.39Weak
anemiaOpen Targets
0.39Weak
systemic juvenile idiopathic arthritisOpen Targets
0.38Weak
idiopathic multicentric Castleman diseaseOpen Targets
0.37Weak
Rheumatoid arthritis systemic juvenileUniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets7
CLAZAKIZUMABPhase III
Interleukin-6 inhibitor
MRA 003 USPhase I
Interleukin-6 inhibitor
systemic lupus erythematosus
OLOKIZUMABApproved
Interleukin-6 inhibitor
immune system disease
PACIBEKITUGPhase II
Interleukin-6 inhibitor
Crohn's disease
SILTUXIMABApproved
Interleukin-6 antagonist
Giant Lymph Node Hyperplasia
SIRUKUMABApproved
Interleukin-6 inhibitor
immune system disease
ZILTIVEKIMABPhase III
Interleukin-6 inhibitor
heart failure
Related Genes
GHRProtein interaction100%IFNAR1Protein interaction100%IFNGR1Protein interaction100%LIFRProtein interaction100%IL9RProtein interaction100%IL20RAProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
34%
Heart
4%
Brain
3%
Ovary
1%
Liver
1%
Gene Interaction Network
Click a node to explore
IL6GHRIFNAR1IFNGR1LIFRIL9RIL20RA
PROTEIN STRUCTURE
Preparing viewer…
PDB1ALU · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.88LoF Tolerant
pLIⓘ
0.20Tolerant
Observed/Expected LoF0.45 [0.24–0.88]
RankingsWhere IL6 stands among ~20K protein-coding genes
  • #4of 20,598
    Most Researched5,468 · top 1%
  • #433of 1,025
    FDA-Approved Drug Targets3
  • #7,830of 17,882
    Most Constrained (LOEUF)0.88
Genes detectedIL6
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Decreased PIBF1/IL6/p-STAT3 during the mid-secretory phase inhibits human endometrial stromal cell proliferation and decidualization.
PMID: 34026283
J Adv Res · 2021
1.00
2
Targeting polarized phenotype of microglia via IL6/JAK2/STAT3 signaling to reduce NSCLC brain metastasis.
PMID: 35194016
Signal Transduct Target Ther · 2022
0.90
3
IL6 genetic perturbation mimicking IL-6 inhibition is associated with lower cardiometabolic risk.
PMID: 40858837
Nat Cardiovasc Res · 2025
0.84
4
Are
PMID: 30787661
J Sports Sci Med · 2019
0.82
5
IL6 Mediates Suppression of T- and NK-cell Function in EMT-associated TKI-resistant EGFR-mutant NSCLC.
PMID: 36595561
Clin Cancer Res · 2023
0.80