F5

The F5 gene provides instructions for making a protein called coagulation factor V. Coagulation factors are a group of related proteins that are essential for normal blood clotting (hemostasis). After an injury, clots protect the body by sealing off damaged blood vessels and preventing further blood loss.

The factor V protein is made chiefly by cells in the liver. The protein circulates in the bloodstream in an inactive form until an injury occurs that damages blood vessels. In response to injury, factor V is activated and binds with another coagulation factor, factor Xa. Active factor V (sometimes written as factor Va) and factor Xa form a complex that converts a molecule called prothrombin to its active form, thrombin. Thrombin then initiates a series of chemical reactions that form a solid blood clot containing a substance called fibrin.

Researchers believe that factor V plays an additional role in controlling hemostasis. A molecule called activated protein C (APC) limits the formation of fibrin blood clots by inactivating factor Va. APC cuts (cleaves) the factor Va protein at specific sites, which partially or completely inactivates it. Once the factor V protein has been modified in this way, it can work with APC to inactivate factor VIIIa, another protein that is essential for normal blood clotting.

factor V Leiden thrombophilia - caused by mutations in the F5 gene

A specific mutation in the F5 gene is responsible for factor V Leiden thrombophilia. Thrombophilia is an increased tendency to form abnormal blood clots in blood vessels. The factor V Leiden mutation changes a single protein building block (amino acid) in the factor V protein. Specifically, this mutation replaces the amino acid arginine with the amino acid glutamine at protein position 506 (written as Arg506Gln). The factor V Leiden mutation affects one of the sites where APC cleaves the factor Va protein, slowing the rate at which factor V is inactivated. This genetic change also prevents factor V from working with APC to inactivate factor VIIIa. As a result, the clotting process continues longer than usual, increasing the chance of developing abnormal blood clots.

other disorders - increased risk from variations of the F5 gene

Some mutations in the F5 gene prevent the production of a functional factor V protein or decrease the amount of the protein in the bloodstream. When present in two copies of the F5 gene, these mutations lead to a rare condition called factor V deficiency or parahemophilia. A reduced amount of functional factor V prevents blood from clotting normally, causing episodes of abnormal bleeding that can range from mild to severe.

A few people have been reported with the factor V Leiden mutation (Arg506Gln) in one copy of the F5 gene in each cell and a mutation associated with factor V deficiency in the other copy of F5. The factor V Leiden mutation results in the production of an abnormal factor V protein that is resistant to inactivation by APC, while the other mutation prevents the production of any factor V protein. People with this combination of mutations appear to have a risk of developing abnormal blood clots similar to the risk faced by people who have two copies of the factor V Leiden mutation. This condition is known as pseudo-homozygous APC resistance.