F9 Gene

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1		Vivi Li	+ 514 word(s)	514	2020-12-15 07:52:33

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/f9

Coagulation Factor IX: The F9 gene provides instructions for making a protein called coagulation factor IX.

genes

1. Normal Function

Coagulation factors are a group of 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 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 XIa. 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.

2. Health Conditions Related to Genetic Changes

2.1 Hemophilia

Mutations in the F9 gene cause a type of hemophilia called hemophilia B. More than 900 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 or reduce the amount of this protein. The altered or missing protein cannot participate effectively in the blood clotting process. As a result, blood clots cannot form 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 sequence 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.

2.2 Warfarin Sensitivity

2.3 Other Disorders

Several rare mutations in the F9 gene cause an increased sensitivity (hypersensitivity) 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. Warfarin works by reducing the amount of active factor IX and three other coagulation proteins.

The mutations responsible for warfarin hypersensitivity each change a single base pair in the F9 gene. These mutations do not cause hemophilia B, and people with these genetic changes only have bleeding problems if they are 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. To avoid these complications, people with warfarin hypersensitivity can be treated with other anticoagulant medications.

3. Other Names for This Gene

Christmas factor
coagulation factor IX (plasma thromboplastic component, Christmas disease, hemophilia B)
FA9_HUMAN
Factor 9
FIX
HEMB
Plasma thromboplastin component
PTC

References

Bolton-Maggs PH, Pasi KJ. Haemophilias A and B. Lancet. 2003 May24;361(9371):1801-9. Review.
Bowen DJ. Haemophilia A and haemophilia B: molecular insights. Mol Pathol.2002 Apr;55(2):127-44. Review. Erratum in: Mol Pathol 2002 Jun;55(3):208.
Chu K, Wu SM, Stanley T, Stafford DW, High KA. A mutation in the propeptide ofFactor IX leads to warfarin sensitivity by a novel mechanism. J Clin Invest. 1996Oct 1;98(7):1619-25.
Giangrande P. Haemophilia B: Christmas disease. Expert Opin Pharmacother. 2005Aug;6(9):1517-24. Review.
Kristensen SR. Warfarin treatment of a patient with coagulation factor IXpropeptide mutation causing warfarin hypersensitivity. Blood. 2002 Oct1;100(7):2676-7.
Lillicrap D. The molecular basis of haemophilia B. Haemophilia. 1998Jul;4(4):350-7. Review.
Oldenburg J, Kriz K, Wuillemin WA, Maly FE, von Felten A, Siegemund A, KeelingDM, Baker P, Chu K, Konkle BA, Lämmle B, Albert T; Study Group on HereditaryWarfarin Sensitivity. Genetic predisposition to bleeding during oralanticoagulant therapy: evidence for common founder mutations (FIXVal-10 andFIXThr-10) and an independent CpG hotspot mutation (FIXThr-10). Thromb Haemost.2001 Mar;85(3):454-7.
Oldenburg J, Quenzel EM, Harbrecht U, Fregin A, Kress W, Müller CR, HertfelderHJ, Schwaab R, Brackmann HH, Hanfland P. Missense mutations at ALA-10 in thefactor IX propeptide: an insignificant variant in normal life but a decisivecause of bleeding during oral anticoagulant therapy. Br J Haematol. 1997Jul;98(1):240-4.
Ulrich S, Brand B, Speich R, Oldenburg J, Asmis L. Congenital hypersensitivityto vitamin K antagonists due to FIX propeptide mutation at locus -10: a (not so) rare cause of bleeding under oral anticoagulant therapy in Switzerland. Swiss MedWkly. 2008 Feb 23;138(7-8):100-7. doi: 2008/07/smw-12022.
Zögg T, Brandstetter H. Activation mechanisms of coagulation factor IX. BiolChem. 2009 May-Jun;390(5-6):391-400. doi: 10.1515/BC.2009.057. Review.

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Subjects: Genetics & Heredity

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Vivi Li

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Entry Collection: MedlinePlus

Update Date: 25 Dec 2020

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