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TNFRSF1A gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

TNFRSF1A gene

The TNFRSF1A gene provides instructions for creating the TNFR1 protein, which plays a critical role in regulating inflammation and cell death.

Normal Function

The TNFRSF1A gene provides instructions for making a protein called tumor necrosis factor receptor 1 (TNFR1). This protein is found spanning the membrane of cells, with part of the TNFR1 protein outside the cell and part of the protein inside the cell. Outside the cell, the TNFR1 protein attaches (binds) to another protein called tumor necrosis factor (TNF). The interaction of the TNF protein with the TNFR1 protein causes the TNFR1 protein to bind to two other TNFR1 proteins, forming a three-protein complex called a trimer. This trimer formation is necessary for the TNFR1 protein to be functional.

The binding of the TNF and TNFR1 proteins causes the TNFR1 protein to send signals inside the cell. Signaling from the TNFR1 protein can trigger either inflammation or self-destruction of the cell (apoptosis). Signaling within the cell initiates a pathway that turns on a protein called nuclear factor kappa B, which triggers inflammation and leads to the production of immune system proteins called cytokines. Apoptosis is initiated when the TNFR1 protein, bound to the TNF protein, is brought into the cell and starts a process known as the caspase cascade.

Health Conditions Related to Genetic Changes

Tumor necrosis factor receptor-associated periodic syndrome

More than 60 mutations in the TNFRSF1A gene have been found to cause tumor necrosis factor receptor-associated periodic syndrome (commonly known as TRAPS). Most of these mutations lead to changes in single protein building blocks (amino acids), typically involving the amino acid cysteine. Cysteines contain sulfur atoms that form connections, called disulfide bonds, with other cysteines. Disulfide bonds help a protein fold by connecting cysteines in different regions of the protein. These bonds stabilize the protein and give it the appropriate shape to carry out its particular function.

When cysteines within the TNFR1 protein are replaced with other amino acids, the disulfide bonds are not formed, and the protein is misfolded. These misfolded proteins are trapped within the cell, unable to get to the cell surface to interact with TNF. Inside the cell, these proteins clump together and are thought to trigger alternative pathways that initiate inflammation. The clumps of protein constantly activate these alternative inflammation pathways, leading to excess inflammation in people with TRAPS. Additionally, because only one copy of the TNFRSF1A gene has a mutation, some normal TNFR1 proteins are produced and can bind to the TNF protein, leading to additional inflammation. It is unclear if disruption of the apoptosis pathway plays a role in the signs and symptoms of TRAPS.

Some people with mutations in the TNFRSF1A gene do not develop TRAPS, or they develop very mild features of the disorder. The reason for this variability is unclear, but researchers believe that other factors, such as additional genetic changes or environmental factors, may play a role in causing TRAPS.

Other Names for This Gene

  • p55
  • p55-R
  • TNF-R
  • TNF-R1
  • TNF-R55
  • TNFR-I
  • TNFR1
  • TNFR55
  • TNR1A_HUMAN
  • tumor necrosis factor binding protein 1
  • tumor necrosis factor receptor superfamily member 1A
  • tumor necrosis factor receptor superfamily, member 1A
  • tumor necrosis factor receptor type 1
  • tumor necrosis factor-alpha receptor

Frequently Asked Questions

TRAPS (tumor necrosis factor receptor-associated periodic syndrome) typically causes recurrent episodes of fever, muscle pain, abdominal pain, and skin rashes. These episodes can last for days or weeks. You should seek medical attention if you experience severe or prolonged symptoms, especially if they are new or worsening, as TRAPS can lead to complications like amyloidosis if not managed.
Diagnosis of TRAPS involves evaluating your symptoms, family history, and ruling out other inflammatory conditions. Genetic testing for mutations in the TNFRSF1A gene is crucial for confirmation. This test usually involves a blood sample to analyze your DNA for specific changes known to cause TRAPS.
TRAPS is inherited in an autosomal dominant pattern. This means if you have one copy of the mutated TNFRSF1A gene, there is a 50% chance with each pregnancy that your child will inherit the mutation and potentially develop TRAPS. Genetic counseling can provide more personalized risk assessment and family planning options.
Treatment for TRAPS focuses on managing inflammation and preventing recurrent flares. This often involves medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) for mild symptoms, corticosteroids for acute attacks, and biologic drugs like TNF inhibitors or IL-1 inhibitors for more severe or frequent flares. Your doctor will tailor a treatment plan based on your specific symptoms and disease activity.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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