F9

The F9 gene provides instructions for making a protein called coagulation factor IX. Coagulation factors are related proteins that are essential for the formation of blood clots. After an injury, clots protect the body by sealing off damaged blood vessels and preventing further blood loss.

Coagulation factor IX is an enzyme made in the liver. This protein circulates in the bloodstream in an inactive form until an injury that damages blood vessels occurs. In response to injury, coagulation factor IX is activated by another coagulation factor called factor XI. The active protein (sometimes written as coagulation factor IXa) interacts with coagulation factor VIII and other molecules. These interactions set off a chain of additional chemical reactions that form a blood clot.

hemophilia - caused by mutations in the F9 gene

Mutations in the F9 gene cause a type of hemophilia called hemophilia B. Hundreds of alterations in this gene have been identified. The most common mutations change single DNA building blocks (base pairs) in the gene. A small percentage of mutations delete or insert multiple base pairs or rearrange segments of DNA within the gene.

Mutations in the F9 gene lead to the production of an abnormal version of coagulation factor IX. The altered protein cannot participate effectively in the blood clotting process and, in some cases, the protein does not work at all. A shortage of this protein prevents blood clots from forming properly in response to injury. These problems with blood clotting lead to excessive bleeding that can be difficult to control. Mutations that completely eliminate the activity of coagulation factor IX result in severe hemophilia. Mutations that reduce but do not eliminate the protein's activity usually cause mild or moderate hemophilia.

Several mutations near the beginning of the F9 gene cause an unusual form of hemophilia known as hemophilia B Leyden. People with these mutations are born with very low levels of functional coagulation factor IX, but hormonal changes cause the levels of this protein to increase gradually during puberty. As a result, adults with hemophilia B Leyden rarely experience episodes of abnormal bleeding.

other disorders - caused by mutations in the F9 gene

Several mutations in the F9 gene cause an increased sensitivity to a drug called warfarin. This medication is an anticoagulant, which means it is used to prevent the formation or growth of abnormal blood clots. The mutations responsible for warfarin hypersensitivity each change a single base pair in the F9 gene. Although people with these mutations do not have hemophilia B, they develop similar problems with blood clotting if treated with warfarin. Warfarin reduces the amount of coagulation factor IX to very low levels in these individuals, which prevents the blood from clotting normally and can lead to recurrent, severe bleeding problems.