Gene Information
Gene Symbol
Entrez Gene ID
Gene Name
Tumor necrosis factor
Chromosomal Location
This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine. (provided by RefSeq, Jul 2008)
GeneCards ID
RefSeq mRNA

Gene Ontology (GO)

GO ID Ontology Definition Evidence Reference
GO:0000060 Biological process Protein import into nucleus, translocation IDA 16280327
GO:0000185 Biological process Activation of MAPKKK activity IDA 15310755
GO:0000187 Biological process Activation of MAPK activity IDA 10748004
GO:0001819 Biological process Positive regulation of cytokine production IDA 17922812
GO:0001934 Biological process Positive regulation of protein phosphorylation IDA 10748004
Protein Information
Protein Name
Tumor necrosis factor, soluble form
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation| The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells
Refseq Proteins
Pfam Accession Pfam ID
PF00229 TNF TNF(Tumour Necrosis Factor) family
Phenotype MIM ID

Associated Diseases

Diseases References
Adipose tissue macrophage (ATM) infiltration 23118428
Cardiovascular disease 21628302, 22944040
Diabetes mellitus type 2 22944040
Hyperandrogenism 22944040, 16522732
Hyperinsulinaemia 17087783

Serum asymmetric dimethylarginine, apelin, and tumor necrosis factor-alpha levels in non-obese women with polycystic ovary syndrome.

Choi Young Sik, Yang Hyo In, Cho Sihyun, Jung Ji Ann, Jeon Young Eun, Kim Hye Yeon, Seo Seok Kyo, Lee Byung Seok
Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Steroids. 2012 Nov;77(13):1352-8. doi: 10.1016/j.steroids.2012.08.005. Epub 2012
Supporting Literature:
PubMed ID Associated gene/s Associated condition Genetic Mutation Diagnostic Criteria Association with PCOS Ethnicity Conclusion
Asymmetric dimethylarginine (ADMA), apelin 
Cardiovascular disease (CVD), including insulin resistance, type 2 diabetes mellitus, obesity, hypertension,hyperandrogenism and dyslipidemia 
ADMA and TNF were positively correlated with total testosterone and free androgen index, whereas apelin was negatively correlated with these parameters. These findings may indicate that non-obese women with PCOS are at an increased risk for CVD, which is further aggravated by hyperandrogenism. 
Adipose tissue macrophage (ATM) infiltration 
NIH criteria 
Women with PCOS had an increase in CD11c expression, CLS density, 5 expression, borderline increase in TNF expression , and a decrease in adiponectin expression in gluteal adipose tissue.  
-1031(T/C) polymorphism of TNF-alpha 
Rotterdam criteria 
Korean population-217 PCOS patients and 144 controls 
The study concludes that the -1031(T/C) polymorphism of TNF-alpha gene is associated with PCOS in a Korean population.  
Patients with PCOS showed significantly higher serum CRP, lymphocytes, monocytes, eosinophilic granulocytes, as well as higher triglycerides (TG), TNF and IL-6 
IL-6, monocyte chemoattractant protein-1 
Low-grade chronic inflammation 
NIH criteria 
The net change in adiponectin secretion in response to IL-6, monocyte chemoattractant protein-1, and TNF-alpha differed between PCOS (decreasing) and control (increasing) adipocytes, although the difference reached significance only for TNF-alpha  

Unreviewed Literature:

PubMed / PMC ID
Title Type of study
26292090, PMC4548699
Levels of Neopterin and other Inflammatory Markers in Obese and Non-Obese Patients with Polycystic Ovary Syndrome. 
Clinical study 
Metformin modulates human leukocyte/endothelial cell interactions and proinflammatory cytokines in polycystic ovary syndrome patients. 
Effect of treatment 
Obesity, but not polycystic ovary syndrome, affects circulating markers of low-grade inflammation in young women without major cardiovascular risk factors. 
Clinical study 
Dual targeting of TNF-?? and free radical toxic stress as a promising strategy to manage experimental polycystic ovary. 
In vitro study 
25889494, PMC4397678
A possible role for AMP-activated protein kinase activated by metformin and AICAR in human granulosa cells. 
Effect of treatment 


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