F5

The F5 gene provides instructions for making a protein called coagulation factor V. Coagulation factors are a group of related proteins that make up the coagulation system, a series of chemical reactions that form blood clots. After an injury, clots seal off blood vessels to stop bleeding and trigger blood vessel repair.

The factor V protein is made primarily by cells in the liver. The protein circulates in the bloodstream in an inactive form until the coagulation system is activated by an injury that damages blood vessels. When coagulation factor V is activated, it interacts with coagulation factor X. The active forms of these two coagulation factors (written as factor Va and factor Xa, respectively) form a complex that converts an important coagulation protein called prothrombin to its active form, thrombin. Thrombin then converts a protein called fibrinogen into fibrin, which is the material that forms the clot.

Coagulation factor V has another role in regulating the coagulation system through its interaction with activated protein C (APC). APC normally inactivates coagulation factor V by cutting (cleaving) it at specific sites. This inactivation slows down the clotting process and prevents clots from growing too large. When coagulation factor V is cleaved at a particular site (protein position 506), it can work with APC to inactivate factor VIIIa, which is another protein that is essential for normal blood clotting.

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

Factor V Leiden is the name of a specific mutation in the F5 gene. This mutation changes a single protein building block (amino acid) in the factor V protein. Specifically, it replaces the amino acid arginine with the amino acid glutamine at protein position 506 (written as Arg506Gln or R506Q). Because position 506 is one of the sites where APC normally cleaves coagulation factor V, the factor V Leiden mutation slows the rate at which APC inactivates this factor. As a result, both the activated form of coagulation factor V and coagulation factor VIIIa persist longer in circulation, increasing the risk of developing an abnormal blood clot. This tendency to form abnormal clots that can block blood vessels is known as thrombophilia.

other disorders - increased risk from variations of the F5 gene

Other mutations in the F5 gene prevent the production of a functional factor V protein or reduce the amount of the protein in the bloodstream. When these mutations are present in both copies of the F5 gene in each cell, they lead to a rare bleeding disorder called factor V deficiency. A reduced amount of functional factor V prevents blood from clotting normally, causing episodes of abnormal bleeding that can be severe. When a mutation is present in only one copy of the factor V gene in each cell, it results in a mild form of factor V deficiency that is usually not associated with abnormal bleeding.

Several people have had the factor V Leiden mutation (Arg506Gln) in one copy of the F5 gene and a mutation associated with factor V deficiency in the other copy of the gene in each cell. 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. This combination of mutations is associated with an increased risk of abnormal blood clots similar to the risk associated with having two copies of the factor V Leiden mutation. This rare condition is known as pseudohomozygous APC resistance or pseudohomozygous factor V Leiden.