F13A1

At least 140 mutations in the F13A1 gene have been found to cause inherited factor XIII deficiency, a rare bleeding disorder. Without treatment, affected individuals have a greatly increased risk of abnormal bleeding episodes, including life-threatening bleeding inside the skull (intracranial hemorrhage). F13A1 gene mutations severely reduce the amount or activity of the A subunit of factor XIII. In most people with these mutations, the level of functional factor XIII in the bloodstream is less than 5 percent of normal. This loss of factor XIII activity weakens new blood clots and prevents them from stopping blood loss effectively.

Several common variations (polymorphisms) in the F13A1 gene have been studied as possible risk factors for diseases involving abnormal blood clotting. The most common F13A1 gene polymorphism changes a single protein building block (amino acid) in a critical part of the A subunit, replacing the amino acid valine with the amino acid leucine at protein position 34 (written as Val34Leu or V34L). This genetic change speeds up the activation of factor XIII. The Val34Leu polymorphism has been studied in relation to heart disease, stroke, recurrent pregnancy loss, and several other conditions. However, the results of these studies have been conflicting, and it remains unclear whether the polymorphism represents a major risk factor for any of these conditions.