F5 gene
The F5 gene provides instructions for making coagulation factor V, a protein essential for normal blood clotting and the regulation of the coagulation system.
Normal Function
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.
Health Conditions Related to Genetic Changes
Factor V deficiency
At least 100 variants (also called mutations) in the F5 gene have been found to cause a rare bleeding disorder called factor V deficiency. These variants prevent the production of functional coagulation factor V or significantly reduce the amount of the protein in the bloodstream. People with this condition typically have less than 10 percent of normal levels of coagulation factor V in their blood; the most severely affected individuals have less than 1 percent. A reduced amount of functional factor V prevents blood from clotting normally, causing episodes of abnormal bleeding that can be severe.
Factor V Leiden thrombophilia
Factor V Leiden is the name of a specific variant in the F5 gene. This variant changes a single protein building block (amino acid) in the factor V protein, replacing arginine with 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 variant 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
Some people have the factor V Leiden variant in one copy of the F5 gene and a variant associated with factor V deficiency in the other copy. This combination is known as pseudohomozygous APC resistance or pseudohomozygous factor V Leiden and is associated with an increased risk of abnormal blood clots. The factor V Leiden variant is also involved in some cases of Budd-Chiari syndrome, a condition characterized by a blockage of blood flow from the liver caused by a blood clot.
