IL6
interleukin 6, the group of Interferons|Interleukin 6 type cytokine family|Interleukins
Basic information
Region (hg38): 7:22725883-22732002
Previous symbols: [ "IFNB2" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (5 variants)
- Inborn genetic diseases (5 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL6 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 8 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 4 | 3 | 3 |
Variants in IL6
This is a list of pathogenic ClinVar variants found in the IL6 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 7-22726602-A-G | INTERLEUKIN 6 POLYMORPHISM | Benign (Mar 01, 2002) | ||
| 7-22727026-C-G | Crohn disease-associated growth failure, susceptibility to • • • Kaposi sarcoma • Diabetes mellitus type 2, susceptibility to • Diabetes mellitus, type 1, susceptibility to • Cholangiocarcinoma | other; risk factor (Dec 10, 2022) | ||
| 7-22727515-C-A | IL6-related disorder | Benign (Jan 29, 2020) | ||
| 7-22727518-C-T | Benign (Dec 31, 2019) | |||
| 7-22727543-C-A | not specified | Uncertain significance (Aug 13, 2021) | ||
| 7-22727592-A-C | not specified | Likely benign (Mar 13, 2023) | ||
| 7-22727607-C-T | Likely benign (Aug 23, 2018) | |||
| 7-22727619-A-C | Likely benign (Jan 01, 2023) | |||
| 7-22728767-G-C | not specified | Uncertain significance (Oct 03, 2022) | ||
| 7-22731419-A-T | Benign (Apr 01, 2023) | |||
| 7-22731483-C-A | not specified | Uncertain significance (Apr 07, 2023) | ||
| 7-22731537-C-T | IL6-related disorder | Benign (Oct 24, 2019) | ||
| 7-22731554-G-C | not specified | Uncertain significance (Jul 22, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| IL6 | protein_coding | protein_coding | ENST00000404625 | 5 | 6119 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.315 | 0.669 | 125739 | 0 | 2 | 125741 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.00294 | 112 | 112 | 0.999 | 0.00000544 | 1389 |
| Missense in Polyphen | 28 | 33.596 | 0.83344 | 445 | ||
| Synonymous | 0.0324 | 43 | 43.3 | 0.994 | 0.00000203 | 415 |
| Loss of Function | 2.04 | 2 | 8.36 | 0.239 | 4.24e-7 | 99 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000884 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig- secreting cells Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation.;
- Disease
- DISEASE: Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]: An inflammatory articular disorder with systemic- onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. {ECO:0000269|PubMed:9769329}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Note=A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men. {ECO:0000269|PubMed:11001912}.;
- Pathway
- Prion diseases - Homo sapiens (human);PI3K-Akt signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Pertussis - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Legionellosis - Homo sapiens (human);Graft-versus-host disease - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Malaria - Homo sapiens (human);Cytosolic DNA-sensing pathway - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Intestinal immune network for IgA production - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);JAK-STAT-Core;Regulation of toll-like receptor signaling pathway;Selenium Micronutrient Network;Vitamin B12 Metabolism;Folate Metabolism;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;TNF alpha Signaling Pathway;Adipogenesis;Spinal Cord Injury;Differentiation Pathway;Hematopoietic Stem Cell Differentiation;Myometrial Relaxation and Contraction Pathways;Overview of nanoparticle effects;Senescence-Associated Secretory Phenotype (SASP);Transcription factor regulation in adipogenesis;Photodynamic therapy-induced AP-1 survival signaling.;Photodynamic therapy-induced NF-kB survival signaling;Lung fibrosis;IL-6 signaling pathway;Hepatitis C and Hepatocellular Carcinoma;TLR4 Signaling and Tolerance;Development and heterogeneity of the ILC family;Protein alkylation leading to liver fibrosis;Interleukin-10 signaling;Interleukin-4 and 13 signaling;Fibrin Complement Receptor 3 Signaling Pathway;PI3K-Akt Signaling Pathway;Cytokines and Inflammatory Response;Senescence and Autophagy in Cancer;T-Cell antigen Receptor (TCR) Signaling Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Toll-like Receptor Signaling Pathway;Signal Transduction;Signaling by Interleukins;il-10 anti-inflammatory signaling pathway;signal transduction through il1r;il 6 signaling pathway;role of erbb2 in signal transduction and oncology;Post-translational protein phosphorylation;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Cellular responses to stress;Post-translational protein modification;Metabolism of proteins;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Immune System;ATF-2 transcription factor network;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);GPCR signaling-G alpha s Epac and ERK;MAPK1 (ERK2) activation;IL-6 signaling;RAF-independent MAPK1/3 activation;Cellular responses to external stimuli;GPCR signaling-G alpha s PKA and ERK;SHP2 signaling;Glucocorticoid receptor regulatory network;MAPK1/MAPK3 signaling;MAPK family signaling cascades;JAK STAT pathway and regulation;GPCR signaling-G alpha i;IL6;MAPK3 (ERK1) activation;IL23-mediated signaling events;IL27-mediated signaling events;AP-1 transcription factor network;amb2 Integrin signaling;Validated transcriptional targets of AP1 family members Fra1 and Fra2;Interleukin-6 signaling;Interleukin-6 family signaling;IL6-mediated signaling events
(Consensus)
Recessive Scores
- pRec
- 0.997
Intolerance Scores
- loftool
- 0.541
- rvis_EVS
- 0.73
- rvis_percentile_EVS
- 85.98
Haploinsufficiency Scores
- pHI
- 0.154
- hipred
- N
- hipred_score
- 0.402
- ghis
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.848
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Il6
- Phenotype
- endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; skeleton phenotype;
Gene ontology
- Biological process
- neutrophil apoptotic process;hepatic immune response;neutrophil mediated immunity;monocyte chemotaxis;positive regulation of acute inflammatory response;positive regulation of leukocyte chemotaxis;acute-phase response;inflammatory response;humoral immune response;positive regulation of cell population proliferation;negative regulation of cell population proliferation;regulation of signaling receptor activity;regulation of vascular endothelial growth factor production;positive regulation of gene expression;negative regulation of lipid storage;cytokine-mediated signaling pathway;platelet activation;endocrine pancreas development;neuron projection development;response to peptidoglycan;positive regulation of chemokine production;positive regulation of interleukin-6 production;negative regulation of collagen biosynthetic process;positive regulation of peptidyl-serine phosphorylation;positive regulation of T cell proliferation;positive regulation of tyrosine phosphorylation of STAT protein;positive regulation of apoptotic process;negative regulation of apoptotic process;positive regulation of MAPK cascade;post-translational protein modification;cellular protein metabolic process;negative regulation of chemokine biosynthetic process;negative regulation of fat cell differentiation;positive regulation of osteoblast differentiation;positive regulation of translation;regulation of angiogenesis;negative regulation of bone resorption;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of JAK-STAT cascade;positive regulation of smooth muscle cell proliferation;positive regulation of peptidyl-tyrosine phosphorylation;negative regulation of neurogenesis;defense response to Gram-negative bacterium;defense response to Gram-positive bacterium;positive regulation of B cell activation;positive regulation of immunoglobulin secretion;positive regulation of DNA-binding transcription factor activity;positive regulation of NF-kappaB transcription factor activity;response to glucocorticoid;defense response to virus;positive regulation of glial cell proliferation;regulation of astrocyte activation;neuron cellular homeostasis;glucagon secretion;interleukin-6-mediated signaling pathway;cellular response to hydrogen peroxide;cellular response to lipopolysaccharide;T-helper 17 cell lineage commitment;regulation of neuroinflammatory response;positive regulation of neuroinflammatory response;regulation of microglial cell activation;regulation of maintenance of permeability of blood-brain barrier;positive regulation of T-helper 2 cell cytokine production;negative regulation of interleukin-1-mediated signaling pathway;positive regulation of type B pancreatic cell apoptotic process
- Cellular component
- extracellular region;extracellular space;endoplasmic reticulum lumen;interleukin-6 receptor complex
- Molecular function
- cytokine activity;interleukin-6 receptor binding;protein binding;growth factor activity