IL6: Polycystic Ovarian Syndrome Database

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IL6

Gene Information

Gene Ontology (GO)

Protein Information

Associated Diseases

Pathways

References

Gene Information

Gene Symbol

IL6

Aliases

BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2, IFNB2, IL-6

Entrez Gene ID

3569

Gene Name

Interleukin 6

Chromosomal Location

7p15.3

HGNC ID

HGNC:6018

Summary

This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The functioning of this gene is implicated in a wide variety of inflammation-associated disease states, including suspectibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

RefSeq DNA

NG_011640.1

RefSeq mRNA

NM_000600.5, NM_001318095.2, NM_001371096.1

e!Ensembl

Gene	ENSG00000136244
Transcript	ENST00000404625, ENST00000426291, ENST00000401651, ENST00000407492, ENST00000401630, ENST00000406575, ENST00000258743
Protein	ENSP00000385675, ENSP00000405150, ENSP00000385718, ENSP00000385043, ENSP00000384928, ENSP00000385227, ENSP00000258743

Gene Ontology (GO)

Show/Hide all(78 )

GO ID	Ontology	Function	Evidence	Reference
GO:0001781	Biological process	Neutrophil apoptotic process	IDA	7595060
GO:0002384	Biological process	Hepatic immune response	IDA	2444978
GO:0002384	Biological process	Hepatic immune response	TAS	12832423
GO:0002446	Biological process	Neutrophil mediated immunity	TAS	16034137
GO:0002548	Biological process	Monocyte chemotaxis	IC	10510402
GO:0002675	Biological process	Positive regulation of acute inflammatory response	IDA	2444978
GO:0002690	Biological process	Positive regulation of leukocyte chemotaxis	TAS	16034137
GO:0006953	Biological process	Acute-phase response	TAS	12832423
GO:0006954	Biological process	Inflammatory response	IDA	10443688
GO:0006959	Biological process	Humoral immune response	IC	3491322
GO:0008284	Biological process	Positive regulation of cell proliferation	IDA	2261637
GO:0008284	Biological process	Positive regulation of cell proliferation	IGI	25809226
GO:0008284	Biological process	Positive regulation of cell proliferation	IMP	18719127
GO:0008285	Biological process	Negative regulation of cell proliferation	TAS	3023045
GO:0010574	Biological process	Regulation of vascular endothelial growth factor production	IDA	8557680
GO:0010575	Biological process	Positive regulation of vascular endothelial growth factor production	IMP	28433754
GO:0010628	Biological process	Positive regulation of gene expression	IDA	19390056
GO:0010718	Biological process	Positive regulation of epithelial to mesenchymal transition	IDA	25916550
GO:0010888	Biological process	Negative regulation of lipid storage	NAS	16464856
GO:0019221	Biological process	Cytokine-mediated signaling pathway	IDA	2261637, 12643274
GO:0030168	Biological process	Platelet activation	TAS	7831669
GO:0031175	Biological process	Neuron projection development	IMP	3264880
GO:0032494	Biological process	Response to peptidoglycan	NAS	16034137
GO:0032722	Biological process	Positive regulation of chemokine production	IDA	10510402
GO:0032722	Biological process	Positive regulation of chemokine production	NAS	16034137
GO:0032755	Biological process	Positive regulation of interleukin-6 production	IDA	10510402
GO:0032966	Biological process	Negative regulation of collagen biosynthetic process	IDA	12419823
GO:0033138	Biological process	Positive regulation of peptidyl-serine phosphorylation	IDA	7508917
GO:0042102	Biological process	Positive regulation of T cell proliferation	IDA	3130269
GO:0042531	Biological process	Positive regulation of tyrosine phosphorylation of STAT protein	IDA	12643274, 19390056
GO:0042531	Biological process	Positive regulation of tyrosine phosphorylation of STAT protein	IMP	28433754
GO:0043065	Biological process	Positive regulation of apoptotic process	IDA	9949178
GO:0043066	Biological process	Negative regulation of apoptotic process	IDA	7595060
GO:0043410	Biological process	Positive regulation of MAPK cascade	IDA	7508917, 12419823
GO:0045380	Biological process	Positive regulation of interleukin-17 biosynthetic process	ISS	25362566
GO:0045599	Biological process	Negative regulation of fat cell differentiation	NAS	16464856
GO:0045669	Biological process	Positive regulation of osteoblast differentiation	IDA	30545407
GO:0045669	Biological process	Positive regulation of osteoblast differentiation	TAS	12372336
GO:0045727	Biological process	Positive regulation of translation	IDA	16732314
GO:0045765	Biological process	Regulation of angiogenesis	IC	8557680
GO:0045893	Biological process	Positive regulation of transcription, DNA-templated	IDA	7749983, 16606666
GO:0045893	Biological process	Positive regulation of transcription, DNA-templated	IMP	17875732
GO:0045944	Biological process	Positive regulation of transcription by RNA polymerase II	IDA	7508917, 16946298, 17324931
GO:0046427	Biological process	Positive regulation of JAK-STAT cascade	IC	17324931
GO:0046427	Biological process	Positive regulation of JAK-STAT cascade	IDA	12419823, 12552091, 17324931
GO:0048661	Biological process	Positive regulation of smooth muscle cell proliferation	IDA	10510402
GO:0050731	Biological process	Positive regulation of peptidyl-tyrosine phosphorylation	IDA	7508917
GO:0050768	Biological process	Negative regulation of neurogenesis	TAS	20018408
GO:0050829	Biological process	Defense response to Gram-negative bacterium	TAS	16034137
GO:0050830	Biological process	Defense response to Gram-positive bacterium	TAS	16034137
GO:0050871	Biological process	Positive regulation of B cell activation	IDA	3491322
GO:0051024	Biological process	Positive regulation of immunoglobulin secretion	IDA	3491322
GO:0051091	Biological process	Positive regulation of DNA-binding transcription factor activity	IDA	7749983
GO:0051092	Biological process	Positive regulation of NF-kappaB transcription factor activity	IDA	12419823
GO:0051384	Biological process	Response to glucocorticoid	IDA	10443688
GO:0051607	Biological process	Defense response to virus	IDA	3023045
GO:0060252	Biological process	Positive regulation of glial cell proliferation	IDA	2104886
GO:0061888	Biological process	Regulation of astrocyte activation	TAS	29702085
GO:0070050	Biological process	Neuron cellular homeostasis	TAS	29702085
GO:0070102	Biological process	Interleukin-6-mediated signaling pathway	IDA	12552091, 16946298
GO:0070301	Biological process	Cellular response to hydrogen peroxide	IDA	19168699
GO:0071222	Biological process	Cellular response to lipopolysaccharide	IMP	23776175
GO:0090091	Biological process	Positive regulation of extracellular matrix disassembly	IMP	26587789
GO:0150077	Biological process	Regulation of neuroinflammatory response	TAS	29702085
GO:0150078	Biological process	Positive regulation of neuroinflammatory response	TAS	26753638
GO:1902512	Biological process	Positive regulation of apoptotic DNA fragmentation	IMP	28433754
GO:1903978	Biological process	Regulation of microglial cell activation	TAS	29702085
GO:1905603	Biological process	Regulation of maintenance of permeability of blood-brain barrier	TAS	29702085
GO:2000676	Biological process	Positive regulation of type B pancreatic cell apoptotic process	TAS	18719127
GO:0005615	Cellular component	Extracellular space	IDA	3023045, 10443688, 16034137
GO:0005896	Cellular component	Interleukin-6 receptor complex	IDA	2261637, 12829785
GO:0005125	Molecular function	Cytokine activity	IDA	3023045, 3491322
GO:0005125	Molecular function	Cytokine activity	NAS	10443688
GO:0005138	Molecular function	Interleukin-6 receptor binding	IPI	12829785
GO:0005138	Molecular function	Interleukin-6 receptor binding	IPI	12829785
GO:0005138	Molecular function	Interleukin-6 receptor binding	NAS	1883960
GO:0005515	Molecular function	Protein binding	IPI	11238858, 12829785, 16169070, 18775332, 25241761
GO:0008083	Molecular function	Growth factor activity	IDA	2261637, 12643274

Protein Information

Protein Name

Interleukin-6, B-cell differentiation factor, B-cell stimulatory factor 2, CTL differentiation factor, hybridoma growth factor, interferon beta-2, interleukin BSF-2

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

Refseq Proteins

NP_000591.1, NP_001305024.1, NP_001358025.1

UniProt

P05231

PDB

1N2Q, 1P9M, 5FUC, 1ALU, 1IL6, 2IL6, 4CNI, 4J4L, 4NI7, 4NI9, 4O9H, 4ZS7

Pfam

Pfam Accession	Pfam ID
PF00489	IL6

Pathways
	KEGG	Reactome
	EGFR tyrosine kinase inhibitor resistance Antifolate resistance Cytokine-cytokine receptor interaction Viral protein interaction with cytokine and cytokine receptor HIF-1 signaling pathway FoxO signaling pathway PI3K-Akt signaling pathway Cellular senescence Toll-like receptor signaling pathway NOD-like receptor signaling pathway Cytosolic DNA-sensing pathway C-type lectin receptor signaling pathway JAK-STAT signaling pathway Hematopoietic cell lineage IL-17 signaling pathway Th17 cell differentiation TNF signaling pathway Intestinal immune network for IgA production Insulin resistance Non-alcoholic fatty liver disease (NAFLD) AGE-RAGE signaling pathway in diabetic complications Prion diseases Salmonella infection Pertussis Legionellosis Yersinia infection Chagas disease (American trypanosomiasis) African trypanosomiasis Malaria Amoebiasis Tuberculosis Hepatitis B Measles Human cytomegalovirus infection Influenza A Human T-cell leukemia virus 1 infection Kaposi sarcoma-associated herpesvirus infection Herpes simplex virus 1 infection Epstein-Barr virus infection Pathways in cancer Transcriptional misregulation in cancer Inflammatory bowel disease (IBD) Rheumatoid arthritis Graft-versus-host disease Hypertrophic cardiomyopathy (HCM)	Interleukin-6 signaling MAPK3 (ERK1) activation MAPK1 (ERK2) activation Senescence-Associated Secretory Phenotype (SASP) Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) Interleukin-10 signaling Interleukin-4 and Interleukin-13 signaling Transcriptional Regulation by VENTX Post-translational protein phosphorylation ADORA2B mediated anti-inflammatory cytokines production CD163 mediating an anti-inflammatory response

Interactions

STRING	MINT	IntAct
ENSP00000304895	P35568	P35568

View interactions

Associated Diseases

Show/Hide all(16 )

Disease group	Disease Name	References
Blood Disorders
	Anemia	15044820
	Angiolymphoid hyperplasia	15182131
Cardiovascular Diseases
	Acute Coronary Syndrome	23305094
	Heart Failure	15135663, 16360360
	Myocardial Infarction	16310260, 15883752
	Hypertensive disease	27292124, 27659729
	Myocardial Failure	15135663, 16360360
	Myocardial Diseases	10716473
	Carditis	25396421
	Myocarditis	25396421
	Myocardial Ischemia	16286589
	Cardiomyopathy	10716473
	Atherosclerosis	19330073
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
	Wilson Disease	25002079
	Hyperoxaluria	16284884
	Atonic seizures	12836160
Digestive System Diseases
	Liver Cirrhosis	12830005, 23274713
	Liver Fibrosis	12830005
	Colitis	24548422, 22410118, 10700533, 21829567
	Liver Diseases	15763341, 7532385
	Hepatitis	15763341, 7532385
	Enteritis	21829567, 10700533
	Cholestasis	28789951, 22461449
	Crohn Disease	21829567, 10700533
Ear Or Mastoid Diseases
Ear Or Mastoid Diseases	Meniere Disease	28787010
Endocrine System Diseases
	Hyperparathyroidism	21350317
	PCOS	30033891, 15193488
Immune System Diseases
	HIV Wasting Syndrome	7979221
	Rheumatoid Arthritis	19192274, 22450443
	Libman-Sacks Disease	18158872
	Lupus Erythematosus	18158872
	Autoimmune Diseases	19077085
	Autoimmune Hepatitis	21227906
Musculoskeletal Diseases
	Osteoporosis	15995586, 9032749
	Polymyositis	7979221
Neoplasms
	Multiple Myeloma	8520508, 19330649, 12855565
	Stomach Cancer	23593346
	Prostate cancer	17196171, 15672864, 19011039, 19240160, 25970160
	Renal Cancer	7834629
	Breast Cancer	19446661, 16298037, 19435922, 17516992
	Liver Cancer	17615358, 20818158, 27022031, 26297436
	Extrahepatic Cholangiocarcinoma	17621267
	Lung Cancer	26372664, 25162674
	Thyroid Cancer	26037280
	Ovarian Cancer	19401270
	Carcinoma	26372664, 22108589
	Intrahepatic Cholangiocarcinoma	17621267
	Leukemia	18006695
	Gastric Cancer	23593346
	Cholangiocarcinoma	17621267
	Vulvar Cancer	16198606
Nervous System Diseases
	Myopathy	7979221
	Cerebral Ischemia	17394460, 15829914
	Seizures	12836160
	Parkinson Disease	21318773
	Middle Cerebral Artery Syndrome	12374626, 21940958, 25257527
	Cerebral Artery Infarction	21940958, 25257527, 12374626
	Brain Infarction	12374626, 21940958, 25257527
	Degenerative Diseases Central Nervous System	12836160
	Neuropathy	18270703
	Stroke	18319729
	Jacksonian Seizure	12836160
	Cerebral Thrombosis	21940958, 12374626, 25257527
	Luft Disease	7979221
	Aseptic Meningitis	10888991
Nutritional and Metabolic Diseases
	Obesity	20141834, 24042701
	Hypercalcemia	10638776
	Metabolic Syndrome X	16644639
	Milk-Alkali Syndrome	10638776
	Gluocose Intolerance	24332041, 19118408, 23094072, 19401444
Psychiatric/Brain disorders
	Mental Depression	25903726, 24491956, 24548241, 25760924, 25350786, 18458677, 22832853, 21448457, 22683764, 25331895, 23813968, 23571152
	Delirium	19269948, 23385102, 21851175, 20471115, 24382617
	Amnesia	9189931
	Autistic Disorder	8964908
	Bipolar Disorder	24120697, 25855618
	Schizophrenia	8067274
	Melancholia	18458677
	Obstructive Sleep Apnea	26564171, 30957979, 26201496, 26276663, 24380782, 26505576, 19218687, 22761257, 19288024, 15325007, 20847078, 24755071
Renal Disorder
	Kidney Failure	21570986, 19539174
	Nephritis	9403216
	Kidney Insufficiency	21570986
	Oxalosis	16284884
	Hemolytic-Uremic Syndrome	15384034
	Glomerulonephritis	9403216
Reproductive disorders
	Pregnancy Complications, Cardiovascular	10716473
	Preeclampsia	26711734, 28947613, 29658087, 31297341, 23790133, 22182686, 22440523, 31683992, 30007972
Respiratory Tract Diseases
	Pleuritis	11181422
	Airway Obstruction	28864214
	Pneumonia	21625544
	Beryllium Disease	8428540
	Chronic Obstructive Pulmonary Disease	28864214
	Pulmonary Fibrosis	25216247, 17266442
	Pleural Diseases	21357438
	Chronic Lung Injury	19762220
Skin and Connective Tissue Diseases
	Psoriasis	16844318
	Eczema	18249437
	Lichenoid Eruptions	18393961
	Pustulosis	16844318
	Leishmaniasis	16540374
	Dermatitis	18249437, 22533443

References

Show/Hide all(4)

PubMed ID	Associated gene/s	Associated condition	Genetic Mutation	Diagnostic Criteria	Association with PCOS	Ethnicity	Conclusion
20103703	SHBG	Insulin sensitivity		Rotterdam criteria	Related		sIL-6R concentration was lower (P = 0.0036) in women with PCOS independently of obesity
20189706		PCOS	-174 G/C		Related	97 Turkish PCOS, 95 Turkish controls	The study suggests that IL-6 promoter region polymorphism may be related to occurrence and metabolic abnormalities seen in PCOS in the Turkish population
24628003		PCOS, obesity			Related	40 women with PCOS and 40 age-matched controls	In this study, serum IL-6 levels were found to be higher in women with PCOS as compared to controls
26141422	IL10, TGF- 1,		1082A/G (IL10), -819A/T(IL10), -522A/G (IL10),-1082A/G (IL10), +874T/A (IFN- ), 10T/C (TGF- 1),-179C/G (IL6),		Related	97 with PCOS, 99 controls	The genetic polymorphisms of cytokines are not associated with PCOS development, but may contribute to common metabolic disorders associated with PCOS

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