Normal Function
The F9 gene provides instructions for making a protein called coagulation factor IX. 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.
Health Conditions Related to Genetic Changes
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.
More About This Health ConditionWarfarin sensitivity
MedlinePlus Genetics provides information about Warfarin sensitivity
More About This Health ConditionOther 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.
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
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
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- Bowen DJ. Haemophilia A and haemophilia B: molecular insights. Mol Pathol. 2002 Apr;55(2):127-44. doi: 10.1136/mp.55.2.127. Erratum In: Mol Pathol 2002 Jun;55(3):208. Citation on PubMed or Free article on PubMed Central
- Chu K, Wu SM, Stanley T, Stafford DW, High KA. A mutation in the propeptide of Factor IX leads to warfarin sensitivity by a novel mechanism. J Clin Invest. 1996 Oct 1;98(7):1619-25. doi: 10.1172/JCI118956. Citation on PubMed or Free article on PubMed Central
- Giangrande P. Haemophilia B: Christmas disease. Expert Opin Pharmacother. 2005 Aug;6(9):1517-24. doi: 10.1517/14656566.6.9.1517. Citation on PubMed
- Kristensen SR. Warfarin treatment of a patient with coagulation factor IX propeptide mutation causing warfarin hypersensitivity. Blood. 2002 Oct 1;100(7):2676-7. doi: 10.1182/blood-2002-06-1753. No abstract available. Citation on PubMed
- Lillicrap D. The molecular basis of haemophilia B. Haemophilia. 1998 Jul;4(4):350-7. doi: 10.1046/j.1365-2516.1998.440350.x. Citation on PubMed
- Oldenburg J, Kriz K, Wuillemin WA, Maly FE, von Felten A, Siegemund A, Keeling DM, Baker P, Chu K, Konkle BA, Lammle B, Albert T; Study Group on Hereditary Warfarin Sensitivity. Genetic predisposition to bleeding during oral anticoagulant therapy: evidence for common founder mutations (FIXVal-10 and FIXThr-10) and an independent CpG hotspot mutation (FIXThr-10). Thromb Haemost. 2001 Mar;85(3):454-7. Citation on PubMed
- Oldenburg J, Quenzel EM, Harbrecht U, Fregin A, Kress W, Muller CR, Hertfelder HJ, Schwaab R, Brackmann HH, Hanfland P. Missense mutations at ALA-10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy. Br J Haematol. 1997 Jul;98(1):240-4. doi: 10.1046/j.1365-2141.1997.2213036.x. Citation on PubMed
- Ulrich S, Brand B, Speich R, Oldenburg J, Asmis L. Congenital hypersensitivity to 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 Med Wkly. 2008 Feb 23;138(7-8):100-7. doi: 10.4414/smw.2008.12022. Citation on PubMed
- Zogg T, Brandstetter H. Activation mechanisms of coagulation factor IX. Biol Chem. 2009 May-Jun;390(5-6):391-400. doi: 10.1515/BC.2009.057. Citation on PubMed
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