F5 gene

Defintion:
Factor V is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor.

Chromosome:1

Position:1q23

Gene Size: 74578 bp (167747816 to 167822393)Complement


No of Exons: 25

Description:

This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance.

Disease :
factor V Leiden thrombophilia

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.

    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.