IL6
Chr 7MultiSomaticADARinterleukin 6
Also known as: BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2, IFNB2, IL-6
This cytokine functions in inflammation, B cell maturation, and serves as an endogenous pyrogen that induces fever, binding to IL6R and then associating with IL6ST/gp130 to trigger intracellular signaling pathways. Mutations are associated with susceptibility to systemic juvenile rheumatoid arthritis, Crohn disease-associated growth failure, and various other inflammatory conditions including diabetes mellitus types 1 and 2. The gene shows multiple inheritance patterns including autosomal dominant, autosomal recessive, and multifactorial inheritance depending on the associated condition.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
IL6 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Metformin for People With CFRD on CFTR Modulator Therapy to Improve Ion Channel Function
RECRUITINGClinical Study of A-319 in the Treatment of Active/Refractory Systemic Lupus Erythematosus
RECRUITINGExpression of GLP1 Receptor on Peripheral Blood Mononuclear Cells in Advanced Peripheral Artery Disease: Paving the Way for GLP1R Agonists Treatment in Chronic Limb Threatening Ischemia
NOT YET RECRUITINGEfficacy and Safety of Tofacitinib in Refractory Blau Syndrome
ENROLLING BY INVITATIONCDH17 CAR-T Therapy in Advanced Malignant Solid Tumors
RECRUITINGRibociclib, Tucatinib, and Trastuzumab for the Treatment of HER2 Positive Breast Cancer
RECRUITINGCharacterization of Clinical Skeletal and Cardiac Impairment in Carriers of DMD and BMD
ACTIVE NOT RECRUITINGOpen-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer
ACTIVE NOT RECRUITINGEFICAC-TTR Trial: Exercise and Nutritional Supplementation in Transthyretin Cardiac Amyloidosis
NOT YET RECRUITINGClinical, Biochemical and Epigenetic Profile of Pediatric Behçet Disease
RECRUITINGSusceptibility to Infectious Diseases in obEsity: an endocRine trAnslational socioLogic Evaluation, "SIDERALE"
RECRUITINGU96-CAR-T-Cells For R/R B-ALL
RECRUITINGExternal Resources
Links to major genomics databases and tools