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TNF

Tumor Necrosis Factor

Gene Number: 7124

Location: 6p21.33

Key Functions: Inflammatory response mediation, immune system activation, apoptosis induction, host defense, and tissue homeostasis


TNF encodes tumor necrosis factor, a potent pro-inflammatory cytokine that serves as a central regulator of immune and inflammatory processes. It is primarily secreted by activated macrophages, T lymphocytes, and natural killer (NK) cells in response to infection, injury, and cellular stress. TNF exerts its effects through two membrane-bound receptors, TNFR1 (p55) and TNFR2 (p75), which activate distinct yet overlapping signaling pathways that coordinate inflammation, apoptosis, and cellular survival.


Through TNFR1, TNF can initiate the NF-κB and MAPK pathways, leading to the transcription of genes involved in inflammation and cell proliferation, or alternatively trigger caspase-mediated apoptosis in damaged or infected cells. TNFR2, which is more restricted to immune and endothelial cells, primarily mediates cell survival, tissue regeneration, and immune regulation. This receptor duality enables TNF to balance protective immune activation with controlled cell death and repair mechanisms.


TNF plays a critical role in host defense, promoting fever, leukocyte recruitment, and acute phase responses essential for pathogen clearance. However, chronic or excessive TNF signaling contributes to pathological inflammation and tissue damage. Overexpression of TNF is strongly implicated in autoimmune and inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, psoriasis, and ankylosing spondylitis.


Because of its pivotal role in chronic inflammation, TNF has become a major therapeutic target in clinical medicine. Anti-TNF biologics, including infliximab, adalimumab, and etanercept, effectively neutralize TNF activity, alleviating inflammatory symptoms and preventing long-term tissue damage in TNF-driven diseases.

SNP ID
Your Genotype
Alternative Alleles
Interpretation
rs1800629
No matching variant or no valid DNA data
A
No interpretation available
rs361525
No matching variant or no valid DNA data
A
No interpretation available
rs1800629 (–308 G>A)
  • GG – Normal risk; typical baseline TNF-α levels (R).

  • AG – Higher risk across multiple inflammatory/autoimmune conditions; linked to increased TNF-α expression (R).

  • AA – Higher risk; often the strongest association with elevated TNF-α and inflammatory phenotypes (R).

Functional effect: The A allele (“TNF2”) upregulates TNF-α transcription from the promoter, raising pro-inflammatory signaling and disease susceptibility in context-dependent ways.


rs361525 (–238 G>A)
  • GG – Normal risk; common baseline (R).

  • AG – Higher risk reported for several conditions; may alter TNF-α production (R).

  • AA – Higher risk (rarer); associations seen in inflammatory and liver-related disorders (R).

Functional effect: The A allele in the TNF-α promoter can modulate expression and downstream inflammation; effect sizes vary by ancestry and disease context.


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