Factor XII deficiency was first described in 1955 and initially named Hageman factor deficiency after the name of the index case (index case is the first individual identified with a particular phenotype). The original cases were described as having markedly prolonged clotting times. The frequency of factor XII deficiency is unknown as individuals carrying mutations in the gene can lack associated symptoms. At least 10 different mutations have been described in the factor XII gene. The symptoms of factor XII deficiency do not manifest with spontaneous or post-surgical bleeding but rather are diagnosed when an incidental activated partial thromboplastin time (aPTT) is markedly prolonged in an otherwise asymptomatic patient. The aPTT is a test used to measure the performance of both the intrinsic and extrinsic coagulation cascades. A definitive diagnosis of factor XII deficiency is accomplished by a modified aPTT using factor XII-deficient plasma.
The factor XII gene (symbol F12) is located on chromosome 5q35.3 spanning 12 kb and composed of 16 exons that encode a 615 amino acid preproprotein. Unlike the majority of eukaryotic mRNA genes, the promoter region of the F12 gene does not contain the typical TATA-box nor the CAAT-box. This gene structure explains why multiple sites of transcriptional initiation have been identified in the F12 gene. The factor XII protein contains multiple domains that are homologous to domains found in tissue type plasminogen activator (tPA) and fibronectin.