F8 gene

The F8 gene (F8-stands for: coagulation factor VIII) is a protein-coding gene located on chomosome Xq28. Gene Ontology (GO) annotations for this gene include oxidoreductase activity and copper ion binding. An important paralog of this gene is F5.

The F8 gene encodes coagulation factor VIII, which is involved in the intrinsic pathway of blood coagulation. Factor VIII is a cofactor for factor IXa, which converts factor X into the activated form Xa in the presence of ^Ca+2 and phospholipids. The F8 gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and is associated with von Willebrand factor in a non-covalent complex. This protein undergoes several cleavage processes. Transcript variant 2 encodes a putative small protein, isoform b, which consists mainly of the phospholipid-binding domain of factor VIIIc. This binding domain is essential for coagulation activity. Defects in this gene lead to hemophilia A, a common recessive X-linked coagulation disorder.

Together with calcium and phospholipids, factor VIII acts as a cofactor for F9/factor IXa when the latter converts F10/factor X into the activated form, factor Xa.

Diseases associated with F8 include hemophilia A (D66) and thrombophilia, X-linked (D68.8), due to a defect in factor VIII.

1. Samelson-Jones BJ et al.(2024) Coagulation factor VIII: biological basis of emerging hemophilia A therapies. Blood 144:2185-2197.