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F12 gene

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

F12 gene

The F12 gene provides instructions for making coagulation factor XII, a protein involved in both blood clotting and the inflammatory response.

Normal Function

The F12 gene provides instructions for making the protein coagulation factor XII. This protein is essential for normal blood clotting; it circulates in an inactive form and is activated upon contact with damaged blood vessel walls. Once activated, it interacts with factor XI to initiate the clotting cascade. Additionally, factor XII plays a role in inflammation. It interacts with plasma kallikrein to release a peptide called bradykinin, which increases vascular permeability and causes the swelling associated with inflammation.

Health Conditions Related to Genetic Changes

Hereditary angioedema

Specific variants in the F12 gene cause a form of hereditary angioedema known as hereditary angioedema with normal C1-INH. These mutations result in a factor XII protein that is more easily activated than normal. This leads to an overproduction of bradykinin, which causes excessive fluid leakage from blood vessels into tissues, resulting in recurrent episodes of severe swelling.

Other disorders

Variants in the F12 gene can also cause factor XII deficiency. This inherited condition is characterized by a shortage of factor XII in the blood. Interestingly, individuals with this deficiency typically do not experience abnormal bleeding or other symptoms. The condition is usually discovered incidentally during routine blood tests, which show that the blood takes longer to clot in a test tube. It remains unclear why this deficiency does not lead to clinical bleeding issues.

Other Names for This Gene

  • coagulation factor XII (Hageman factor)
  • FA12_HUMAN
  • HAE3
  • HAEX
  • HAF
  • Hageman factor

Frequently Asked Questions

Hereditary angioedema caused by F12 mutations, often called HAE with normal C1-INH, presents with similar symptoms of recurrent swelling but is distinguished by normal levels of the C1 inhibitor protein. In standard HAE, the C1 inhibitor is low or dysfunctional, whereas in F12-related HAE, the factor XII protein is hyperactive, leading to excessive bradykinin production. This distinction is critical for diagnosis because standard C1-INH tests will appear normal, requiring specific genetic testing or functional assays to identify the F12 variant.
Individuals with factor XII deficiency typically do not experience spontaneous bleeding or significant bleeding during surgery, childbirth, or trauma, despite having prolonged clotting times in laboratory tests. The deficiency is often clinically silent, meaning the body’s other clotting mechanisms compensate effectively. However, because the aPTT test is prolonged, it is crucial to inform surgeons and anesthesiologists about the condition to prevent unnecessary blood product transfusions, which carry their own risks and are generally not indicated for this specific deficiency.
Early warning signs of an F12-related HAE attack often include a tingling or burning sensation in the affected area, such as the hands, feet, or abdomen, before visible swelling appears. Unlike allergic reactions, HAE attacks are not triggered by specific allergens like food or insect stings and do not respond to antihistamines or epinephrine. The swelling is non-pitting and can last for several days, and abdominal attacks may cause severe pain, nausea, and vomiting that can mimic a surgical emergency.
While factor XII is involved in the clotting cascade, mutations in the F12 gene that cause hereditary angioedema are primarily associated with excessive inflammation and swelling rather than an increased risk of pathological blood clots. However, because factor XII plays a role in both hemostasis and inflammation, researchers are still studying the long-term cardiovascular risks. Current clinical guidance does not classify F12-related HAE as a primary thrombophilia, but patients should maintain open communication with their hematologist regarding any new symptoms related to circulation.
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.