Gene:
F5
coagulation factor V (proaccelerin, labile factor)

last updated 08/10/2011

1. DPWG Guideline for hormonal contraceptives for systemic use and F5

Summary

In individuals who carry the Factor V Leiden allele and have a family history of thrombotic events, estrogen-containing oral contraceptives should be avoided and alternative forms of contraception used.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for hormonal contraceptives for systemic use based on Factor V Leiden (FVL, or F5) genotype [Article:21412232]. They suggest that in individuals who carry the Factor V Leiden allele and have a family history of thrombotic events, estrogen-containing oral contraceptives should be avoided and alternative forms of contraception used.

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
F5 homozygous rs6025 TTPositive (family) history of thrombotic events: avoid estrogen-containing oral contraceptives and select alternative (e.g., copper intrauterine device, progestin-only contraceptive). Negative (family) history of thrombotic events: avoid additional risk factors (e.g., obesity, smoking).Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x109/l; leucopenia 1.0-2.0x109/l; thrombocytopenia 25-50x109/l; severe diarrhea
F5 heterozygous rs6025 CTPositive (family) history of thrombotic events: avoid estrogen-containing oral contraceptives and select alternative (e.g., copper intrauterine device, progestin-only contraceptive). Negative (family) history of thrombotic events: avoid additional risk factors (e.g., obesity, smoking).Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x109/l; leucopenia 1.0-2.0x109/l; thrombocytopenia 25-50x109/l; severe diarrhea
  • *See Methods or [Article:18253145] for definition of "good" and "moderate" quality.
  • S: statistically significant difference.


Annotated Labels

  1. FDA Label for eltrombopag and F5,SERPINC1
  2. FDA Label for tamoxifen and ESR1,ESR2,F2,F5
  3. EMA Label for eltrombopag and F5,SERPINC1
  4. EMA Label for ethinyl estradiol,norelgestromin and F5
  5. HCSC Label for eltrombopag and F5,SERPINC1
  6. HCSC Label for drospirenone,ethinyl estradiol and F5,PROC,PROS1,SERPINC1
  7. HCSC Label for ethinyl estradiol,norelgestromin and F2,F5,MTHFR,PROC,PROS1,SERPINC1

last updated 10/25/2013

1. FDA Label for eltrombopag and F5,SERPINC1

Actionable PGx

Summary

The FDA-approved drug label for eltrombopag (PROMACTA) notes that patients taking the drug have an increased risk of thromboembolism if they have antithrombin III deficiency (SERPINC1) or Factor V Leiden (F5).

There's more of this label. Read more.



last updated 10/25/2013

3. EMA Label for eltrombopag and F5,SERPINC1

Actionable PGx

Summary

The EMA European Public Assessment Report (EPAR) highlights that caution should be taken when administering eltrombopag in patients with known risk factors for thromboembolism, including Factor V Leiden (F5 gene) and ATIII deficiency (SERPINC1 gene).

There's more of this label. Read more.


last updated 05/08/2014

4. EMA Label for ethinyl estradiol,norelgestromin and F5

Genetic testing required

Summary

The EMA European Public Assessment Report (EPAR) for norelgestromin and ethinyl estradiol (Evra) contains information regarding its contraindication in women with known predisposition to venous thromboembolism (including Factor V Leiden, rs6025).

There's more of this label. Read more.


5. HCSC Label for eltrombopag and F5,SERPINC1

Actionable PGx

Summary

The product monograph for eltrombopag (REVOLADE) states that caution should be used when administering the drug to patients with risk factors for thromboembolism, such as Factor V Leiden mutation (rs6025 in F5) and antithrombin III deficiency (SERPINC1).

There's more of this label. Read more.


6. HCSC Label for drospirenone,ethinyl estradiol and F5,PROC,PROS1,SERPINC1

Actionable PGx

Summary

The product monograph for drospirenone and ethinyl estradiol (YAZ) states that the drug is contraindicated in women with Factor V Leiden mutation, antithrombin-III-deficiency, protein C deficiency and protein S deficiency (among other contraindications), due to the risk for arterial or venous thrombosis.

There's more of this label. Read more.


7. HCSC Label for ethinyl estradiol,norelgestromin and F2,F5,MTHFR,PROC,PROS1,SERPINC1

Actionable PGx

Summary

The product monograph for norelgestromin and ethinyl estradiol (EVRA) states that the drug is contraindicated in women with Factor V Leiden mutation, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinaemia due to mutations in the MTHFR gene and prothrombin mutation G20210A (among other contraindications), due to the risk for arterial or venous thrombosis.

There's more of this label. Read more.


PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

List of all variant annotations for F5

Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs6018 NC_000001.10:g.169511878T>G, NC_000001.11:g.169542640T>G, NG_011806.1:g.48892A>C, NM_000130.4:c.2450A>C, NP_000121.2:p.Asn817Thr, rs13306324, rs52823616, rs60636513
T > G
SNP
N817T
rs6025 NC_000001.10:g.169519049T=, NC_000001.10:g.169519049T>C, NC_000001.11:g.169549811C=, NC_000001.11:g.169549811C>T, NG_011806.1:g.41721G=, NG_011806.1:g.41721G>A, NM_000130.4:c.1601G=, NM_000130.4:c.1601G>A, NP_000121.2:p.Arg534=, NP_000121.2:p.Arg534Gln, rs1801711, rs60031897
T > C
SNP
R534Q
No VIP available No Clinical Annotations available VA
rs7542281 NC_000001.10:g.169536439C>T, NC_000001.11:g.169567201C>T, NG_011806.1:g.24331G>A, NM_000130.4:c.373+5020G>A, rs9332558
C > T
SNP
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Alternate Names:  None
Alternate Symbols:  None
PharmGKB Accession Id: PA159

Details

Cytogenetic Location: chr1 : q24.2 - q24.2
GP mRNA Boundary: chr1 : 169481192 - 169555769
GP Gene Boundary: chr1 : 169478192 - 169565769
Strand: minus

Visualization

UCSC has a Genome Browser that you can use to view PharmGKB annotations for this gene in context with many other sources of information.

View on UCSC Browser
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

Factor V is an essential coagulation cofactor that enhances thrombin activation by factor Xa. In 1987, Jenny et al. determined the primary structure of the factor V gene, F5, by cloning from a human fetal liver cDNA library. Riddell et al. and Wang et al. mapped the gene to chromosome 1q23. F5 is 72,313 bp with a 6,672 bp coding region consisting of 25 exons. Factor V is a 330 kDa single chain glycoprotein comprised of 2,224 amino acid residues. [Articles:3220473, 3110773, 11950687, 7989361, 2827731]

A total of 433 validated polymorphisms are described in the dbSNP database; 40 of these are in the coding region and 22 result in an amino acid change. Based on SeattleSNPsdata, 181 SNPs have an allele frequency greater than 5% and of the 31 common coding polymorphisms, 18 are nonsynonymous. The most commonly studied variant in F5 is the 1691G>A substitution (Arg506Gln; the nucleotide position relative to start of sequence for F5 published by Jenny et al. PMID:3110773, which is also known as Factor V Leiden (FVL). FVL prevents deactivation of coagulation factor V by activated protein C. [Article:8164741]

Venous thromboembolism (VTE) is the most well-studied phenotype associated with FVL. The risk of VTE is greater among individuals with FVL, particularly among smokers and women using oral contraceptives or estrogen hormone replacement therapy. The relationship with arterial thrombosis is less clear. FVL has also been implicated as a risk factor for small bowel infarction, mortality in sepsis, restensosis, Budd-Chiari syndrome, obstetric complications such as VTE, preeclampsia, abruptio placentae, fetal growth retardation, and late fetal loss, ischemic stroke and porencephaly. Numerous variations in F5 have been associated with states of thrombophilia or parahemophilia, however few have been extensively studied. [Articles:16113779, 14574075, 16651467, 11859850, 12069454, 7877648, 9207293, 9245936, 9878639, 10666427, 11435304, 12070000, 16606808, 15534175, 14660985, 15118525]

Citation
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
History

Submitted by Jennifer Bushwitz, Michael A. Pacanowski, Julie A. Johnson (PEAR)

Key Publications
  1. Effect of Factor V Leiden and prothrombin G20210-->A mutations on thromboembolic risk in the national surgical adjuvant breast and bowel project breast cancer prevention trial. Journal of the National Cancer Institute. 2006. Abramson Neil, Costantino Joseph P, Garber Judy E, Berliner Nancy, Wickerham D Lawrence, Wolmark Norman. PubMed
  2. Polymorphism in the beta2-adrenergic receptor and lipoprotein lipase genes as risk determinants for idiopathic venous thromboembolism: a multilocus, population-based, prospective genetic analysis. Circulation. 2006. Zee Robert Y L, Cook Nancy R, Cheng Suzanne, Erlich Henry A, Lindpaintner Klaus, Ridker Paul M. PubMed
  3. Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review. Archives of internal medicine. 2006. Ho Wai Khoon, Hankey Graeme J, Quinlan Daniel J, Eikelboom John W. PubMed
  4. Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study. Health technology assessment (Winchester, England). 2006. Wu O, Robertson L, Twaddle S, Lowe G D O, Clark P, Greaves M, Walker I D, Langhorne P, Brenkel I, Regan L, Greer I. PubMed
  5. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet. 2006. Ye Zheng, Liu Eugene H C, Higgins Julian P T, Keavney Bernard D, Lowe Gordon D O, Collins Rory, Danesh John. PubMed
  6. Effect of various genetic polymorphisms on the incidence and outcome of severe sepsis. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2006. Sipahi Tansu, Pocan Hatice, Akar Nejat. PubMed
  7. Expression of the normal factor V allele modulates the APC resistance phenotype in heterozygous carriers of the factor V Leiden mutation. Journal of thrombosis and haemostasis : JTH. 2005. Brugge J M, Simioni P, Bernardi F, Tormene D, Lunghi B, Tans G, Pagnan A, Rosing J, Castoldi E. PubMed
  8. Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration. Circulation. 2005. Straczek Céline, Oger Emmanuel, Yon de Jonage-Canonico Marianne Beau, Plu-Bureau Geneviève, Conard Jacqueline, Meyer Guy, Alhenc-Gelas Martine, Lévesque Hervé, Trillot Nathalie, Barrellier Marie-Thérèse, Wahl Denis, Emmerich Joseph, Scarabin Pierre-Yves, Estrogen and Thromboembolism Risk (ESTHER) Study Group. PubMed
  9. Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis. British journal of haematology. 2005. Wu Olivia, Robertson Lindsay, Twaddle Sara, Lowe Gordon, Clark Peter, Walker Isobel, Brenkel Ivan, Greaves Mike, Langhorne Peter, Regan Lesley, Greer Ian, Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. PubMed
  10. Matched case-control study on factor V Leiden and the prothrombin G20210A mutation in patients with ischemic stroke/transient ischemic attack up to the age of 60 years. Stroke; a journal of cerebral circulation. 2005. Lalouschek Wolfgang, Schillinger Martin, Hsieh Kety, Endler Georg, Tentschert Susanne, Lang Wilfried, Cheng Suzanne, Mannhalter Christine. PubMed
  11. Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thrombosis and haemostasis. 2005. Wu Olivia, Robertson Lindsay, Langhorne Peter, Twaddle Sara, Lowe Gordon D O, Clark Peter, Greaves Mike, Walker Isobel D, Brenkel Ivan, Regan Lesley, Greer Ian A. PubMed
  12. Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. Archives of neurology. 2004. Casas Juan P, Hingorani Aroon D, Bautista Leonelo E, Sharma Pankaj. PubMed
  13. Estrogen plus progestin and risk of venous thrombosis. JAMA : the journal of the American Medical Association. 2004. Cushman Mary, Kuller Lewis H, Prentice Ross, Rodabough Rebecca J, Psaty Bruce M, Stafford Randall S, Sidney Steven, Rosendaal Frits R, Women's Health Initiative Investigators. PubMed
  14. Impaired APC cofactor activity of factor V plays a major role in the APC resistance associated with the factor V Leiden (R506Q) and R2 (H1299R) mutations. Blood. 2004. Castoldi Elisabetta, Brugge Jeroen M, Nicolaes Gerry A F, Girelli Domenico, Tans Guido, Rosing Jan. PubMed
  15. Effect of factor V Leiden polymorphism in severe sepsis and on treatment with recombinant human activated protein C. Critical care medicine. 2004. Yan S Betty, Nelson David R. PubMed
  16. Factor V Leiden polymorphism modifies sepsis outcome: evidence from animal studies. Critical care medicine. 2004. Weiler Hartmut, Kerlin Bryce, Lytle Mary C. PubMed
  17. Factor V Leiden: a disorder of factor V anticoagulant function. Current opinion in hematology. 2004. Castoldi Elisabetta, Rosing Jan. PubMed
  18. Factor V Leiden and the risk for venous thromboembolism in the adult Danish population. Annals of internal medicine. 2004. Juul Klaus, Tybjaerg-Hansen Anne, Schnohr Peter, Nordestgaard Børge G. PubMed
  19. Effect of second- and third-generation oral contraceptives on the protein C system in the absence or presence of the factor VLeiden mutation: a randomized trial. Blood. 2004. Kemmeren Jeanet M, Algra Ale, Meijers Joost C M, Tans Guido, Bouma Bonno N, Curvers Joyce, Rosing Jan, Grobbee Diederick E. PubMed
  20. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. American heart journal. 2003. Kim Robert J, Becker Richard C. PubMed
  21. Coinheritance of Factor V (FV) Leiden enhances thrombin formation and is associated with a mild bleeding phenotype in patients homozygous for the FVII 9726+5G>A (FVII Lazio) mutation. Blood. 2003. Castoldi Elisabetta, Govers-Riemslag Jose W P, Pinotti Mirko, Bindini Debora, Tans Guido, Berrettini Mauro, Mazzucconi Maria Gabriella, Bernardi Francesco, Rosing Jan. PubMed
  22. Survival advantage associated with heterozygous factor V Leiden mutation in patients with severe sepsis and in mouse endotoxemia. Blood. 2003. Kerlin Bryce A, Yan S Betty, Isermann Berend H, Brandt John T, Sood Rashmi, Basson Bruce R, Joyce David E, Weiler Hartmut, Dhainaut Jean-Francois. PubMed
  23. Factor V I359T: a novel mutation associated with thrombosis and resistance to activated protein C. British journal of haematology. 2003. Mumford A D, McVey J H, Morse C V, Gomez K, Steen M, Norstrom E A, Tuddenham E G D, Dahlback B, Bolton-Maggs P H B. PubMed
  24. Inherited and acquired risk factors for venous thromboembolic disease among women taking tamoxifen to prevent breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2003. Duggan Catherine, Marriott Kevin, Edwards Rob, Cuzick Jack. PubMed
  25. Differential effects of oral and transdermal estrogen/progesterone regimens on sensitivity to activated protein C among postmenopausal women: a randomized trial. Arteriosclerosis, thrombosis, and vascular biology. 2003. Oger Emmanuel, Alhenc-Gelas Martine, Lacut Karine, Blouch Marie-Thérèse, Roudaut Nathalie, Kerlan Véronique, Collet Michel, Abgrall Jean-François, Aiach Martine, Scarabin Pierre-Yves, Mottier Dominique, SARAH Investigators. PubMed
  26. Prothrombotic coagulation defects and cardiovascular risk factors in young women with acute myocardial infarction. British journal of haematology. 2003. Tanis Bea C, Bloemenkamp Daisy G M, van den Bosch Maurice A A J, Kemmeren Jeanet M, Algra Ale, van de Graaf Yolanda, Rosendaal Frits R. PubMed
  27. Factor V Leiden and risk of ischemic stroke in nonvalvular atrial fibrillation: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. Journal of thrombosis and thrombolysis. 2003. Go Alan S, Reed Guy L, Hylek Elaine M, Phillips Kathleen A, Liu Lin, Henault Lori E, Selby Joe V, Singer Daniel E. PubMed
  28. Screening for inherited thrombophilia: indications and therapeutic implications. Haematologica. 2002. De Stefano Valerio, Rossi Elena, Paciaroni Katia, Leone Giuseppe. PubMed
  29. Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses. Blood. 2002. Juul Klaus, Tybjaerg-Hansen Anne, Steffensen Rolf, Kofoed Steen, Jensen Gorm, Nordestgaard Børge Grønne. PubMed
  30. Effect of second- and third-generation oral contraceptives on fibrinolysis in the absence or presence of the factor V Leiden mutation. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2002. Kemmeren J M, Algra A, Meijers J C M, Bouma B N, Grobbee D E. PubMed
  31. Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease. Arteriosclerosis, thrombosis, and vascular biology. 2002. Herrington David M, Vittinghoff Eric, Howard Timothy D, Major David A, Owen John, Reboussin David M, Bowden Donald, Bittner Vera, Simon Joel A, Grady Deborah, Hulley Stephen B. PubMed
  32. Venous thromboembolism in young women; role of thrombophilic mutations and oral contraceptive use. European heart journal. 2002. Legnani C, Palareti G, Guazzaloca G, Cosmi B, Lunghi B, Bernardi F, Coccheri S. PubMed
  33. Factor V and thrombotic disease: description of a janus-faced protein. Arteriosclerosis, thrombosis, and vascular biology. 2002. Nicolaes Gerry A F, Dahlbäck Björn. PubMed
  34. Factor V Leiden (G1691A) and prothrombin gene G20210A mutations as potential risk factors for venous thromboembolism after total hip or total knee replacement surgery. Thrombosis and haemostasis. 2002. Wåhlander K, Larson G, Lindahl T L, Andersson C, Frison L, Gustafsson D, Bylock A, Eriksson B I. PubMed
  35. Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis. British journal of haematology. 2002. Rosendaal F R, Vessey M, Rumley A, Daly E, Woodward M, Helmerhorst F M, Lowe G D O. PubMed
  36. Effects of second and third generation oral contraceptives and their respective progestagens on the coagulation system in the absence or presence of the factor V Leiden mutation. Thrombosis and haemostasis. 2002. Kemmeren J M, Algra A, Meijers J C M, Bouma B N, Grobbee D E. PubMed
  37. Testing for factor V Leiden in patients with pulmonary or venous thromboembolism: a cost-effectiveness analysis. Medical decision making : an international journal of the Society for Medical Decision Making. 2002. Eckman Mark H, Singh Sushil K, Erban John K, Kao Grace. PubMed
  38. Hormone replacement therapy and acquired resistance to activated protein C: results of a randomized, double-blind, placebo-controlled trial. British journal of haematology. 2001. Høibraaten E, Mowinckel M C, de Ronde H, Bertina R M, Sandset P M. PubMed
  39. A prospective study of asymptomatic carriers of the factor V Leiden mutation to determine the incidence of venous thromboembolism. Annals of internal medicine. 2001. Middeldorp S, Meinardi J R, Koopman M M, van Pampus E C, Hamulyák K, van Der Meer J, Prins M H, Büller H R. PubMed
  40. Risk of thrombosis associated with oral contraceptives of women from 97 families with inherited thrombophilia: high risk of thrombosis in carriers of the G20210A mutation of the prothrombin gene. Haematologica. 2001. Santamaría A, Mateo J, Oliver A, Menéndez B, Souto J C, Borrell M, Soria J M, Tirado I, Fontcuberta J. PubMed
  41. Five novel mutations in the gene for human blood coagulation factor V associated with type I factor V deficiency. Blood. 2001. van Wijk R, Nieuwenhuis K, van den Berg M, Huizinga E G, van der Meijden B B, Kraaijenhagen R J, van Solinge W W. PubMed
  42. Factor V R506Q mutation-Leiden: an independent risk factor for venous thrombosis but not coronary artery disease. Journal of thrombosis and thrombolysis. 2001. Irani-Hakime N, Tamim H, Elias G, Choueiry S, Kreidy R, Daccache J L, Almawi W Y. PubMed
  43. Population genetics of factor V Leiden in Europe. Blood cells, molecules & diseases. 2001. Lucotte G, Mercier G. PubMed
  44. Extended anticoagulation for prevention of recurrent venous thromboembolism in carriers of factor V Leiden--cost-effectiveness analysis. Thrombosis and haemostasis. 2000. Marchetti M, Pistorio A, Barosi G. PubMed
  45. The prevalence of factor V R506Q mutation-Leiden among apparently healthy Lebanese. American journal of hematology. 2000. Irani-Hakime N, Tamim H, Kreidy R, Almawi W Y. PubMed
  46. Are factor V Leiden carriers who use oral contraceptives at extreme risk for venous thromboembolism?. The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception. 2000. Spannagl M, Heinemann L A, Schramm W. PubMed
  47. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium. The New England journal of medicine. 2000. Gerhardt A, Scharf R E, Beckmann M W, Struve S, Bender H G, Pillny M, Sandmann W, Zotz R B. PubMed
  48. Coagulation factors II, V, VII, and X, prothrombin gene 20210G-->A transition, and factor V Leiden in coronary artery disease: high factor V clotting activity is an independent risk factor for myocardial infarction. Arteriosclerosis, thrombosis, and vascular biology. 1999. Redondo M, Watzke H H, Stucki B, Sulzer I, Biasiutti F D, Binder B R, Furlan M, Lämmle B, Wuillemin W A. PubMed
  49. Cleavage of factor V at Arg 506 by activated protein C and the expression of anticoagulant activity of factor V. Blood. 1999. Thorelli E, Kaufman R J, Dahlbäck B. PubMed
  50. Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arteriosclerosis, thrombosis, and vascular biology. 1999. Martinelli I, Taioli E, Bucciarelli P, Akhavan S, Mannucci P M. PubMed
  51. Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism: prevalence and risk assessment. Arteriosclerosis, thrombosis, and vascular biology. 1999. Salomon O, Steinberg D M, Zivelin A, Gitel S, Dardik R, Rosenberg N, Berliner S, Inbal A, Many A, Lubetsky A, Varon D, Martinowitz U, Seligsohn U. PubMed
  52. Increased frequency of genetic thrombophilia in women with complications of pregnancy. The New England journal of medicine. 1999. Kupferminc M J, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A, Fait G, Lessing J B. PubMed
  53. Genetic risk factors in acute coronary disease. Haemostasis. 1999. Araújo F, Santos A, Araújo V, Henriques I, Monteiro F, Meireles E, Moreira I, David D, Maciel M J, Cunha-Ribeiro L M. PubMed
  54. Interaction of coagulation defects and cardiovascular risk factors: increased risk of myocardial infarction associated with factor V Leiden or prothrombin 20210A. Circulation. 1998. Doggen C J, Cats V M, Bertina R M, Rosendaal F R. PubMed
  55. Decision analysis model of prolonged oral anticoagulant treatment in factor V Leiden carriers with first episode of deep vein thrombosis. BMJ (Clinical research ed.). 1998. Sarasin F P, Bounameaux H. PubMed
  56. Third generation oral contraceptives and heritable thrombophilia as risk factors of non-fatal venous thromboembolism. Thrombosis and haemostasis. 1998. Andersen B S, Olsen J, Nielsen G L, Steffensen F H, Sørensen H T, Baech J, Gregersen H. PubMed
  57. Prevalence of the factor V-Leiden mutation in four distinct American ethnic populations. American journal of medical genetics. 1997. Gregg J P, Yamane A J, Grody W W. PubMed
  58. Factor V Leiden mutation and the risks for thromboembolic disease: a clinical perspective. Annals of internal medicine. 1997. Price D T, Ridker P M. PubMed
  59. Leiden factor V mutation in four patients with small bowel infarctions. Gastroenterology. 1997. Heresbach D, Pagenault M, Gueret P, Crenn P, Heresbach-Le Berre N, Malledant Y, Fauchet R, Horellou M H, Silver J, Messing B, Bretagne J F. PubMed
  60. Prevalence of the factor V Leiden mutation in hepatic and portal vein thrombosis. Gut. 1997. Mahmoud A E, Elias E, Beauchamp N, Wilde J T. PubMed
  61. Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women. Blood. 1997. Rosendaal F R, Siscovick D S, Schwartz S M, Beverly R K, Psaty B M, Longstreth W T, Raghunathan T E, Koepsell T D, Reitsma P H. PubMed
  62. Prevalence of factor V Leiden mutation in non-European populations. Thrombosis and haemostasis. 1997. Pepe G, Rickards O, Vanegas O C, Brunelli T, Gori A M, Giusti B, Attanasio M, Prisco D, Gensini G F, Abbate R. PubMed
  63. Prevalence of factor V Leiden mutation in various populations. Genetic epidemiology. 1997. Herrmann F H, Koesling M, Schr¿der W, Altman R, Jiménez Bonilla R, Lopaciuk S, Perez-Requejo J L, Singh J R. PubMed
  64. Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening. JAMA : the journal of the American Medical Association. 1997. Ridker P M, Miletich J P, Hennekens C H, Buring J E. PubMed
  65. Elevated levels of prothrombin activation fragment 1 + 2 in plasma from patients with heterozygous Arg506 to Gln mutation in the factor V gene (APC-resistance) and/or inherited protein S deficiency. Thrombosis and haemostasis. 1996. Zöller B, Holm J, Svensson P, Dahlbäck B. PubMed
  66. Ischemic stroke in the elderly. Role of the common factor V mutation causing resistance to activated protein C. Stroke; a journal of cerebral circulation. 1996. Press R D, Liu X Y, Beamer N, Coull B M. PubMed
  67. Molecular mechanisms of activated protein C resistance. Properties of factor V isolated from an individual with homozygosity for the Arg506 to Gln mutation in the factor V gene. The Biochemical journal. 1996. Aparicio C, Dahlbäck B. PubMed
  68. Evidence against heterozygous coagulation factor V 1691 G-->A mutation with resistance to activated protein C being a risk factor for coronary artery disease and myocardial infarction. Journal of molecular medicine (Berlin, Germany). 1995. Prohaska W, Mannebach H, Schmidt M, Gleichmann U, Kleesiek K. PubMed
  69. World distribution of factor V Leiden. Lancet. 1995. Rees D C, Cox M, Clegg J B. PubMed
  70. The mechanism of inactivation of human platelet factor Va from normal and activated protein C-resistant individuals. The Journal of biological chemistry. 1995. Camire R M, Kalafatis M, Cushman M, Tracy R P, Mann K G, Tracy P B. PubMed
  71. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. The New England journal of medicine. 1995. Ridker P M, Hennekens C H, Lindpaintner K, Stampfer M J, Eisenberg P R, Miletich J P. PubMed
  72. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood. 1995. Rosendaal F R, Koster T, Vandenbroucke J P, Reitsma P H. PubMed
  73. Characterization of the molecular defect in factor VR506Q. The Journal of biological chemistry. 1995. Kalafatis M, Bertina R M, Rand M D, Mann K G. PubMed
  74. The mechanism of inactivation of human factor V and human factor Va by activated protein C. The Journal of biological chemistry. 1994. Kalafatis M, Rand M D, Mann K G. PubMed
  75. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet. 1994. Vandenbroucke J P, Koster T, Briët E, Reitsma P H, Bertina R M, Rosendaal F R. PubMed
  76. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 1994. Bertina R M, Koeleman B P, Koster T, Rosendaal F R, Dirven R J, de Ronde H, van der Velden P A, Reitsma P H. PubMed
  77. Localization of the gene encoding human factor V to chromosome 1q21-25. Genomics. 1988. Wang H, Riddell D C, Guinto E R, MacGillivray R T, Hamerton J L. PubMed
  78. Cloning of cDNAs coding for the heavy chain region and connecting region of human factor V, a blood coagulation factor with four types of internal repeats. Biochemistry. 1987. Kane W H, Ichinose A, Hagen F S, Davie E W. PubMed
  79. Complete cDNA and derived amino acid sequence of human factor V. Proceedings of the National Academy of Sciences of the United States of America. 1987. Jenny R J, Pittman D D, Toole J J, Kriz R W, Aldape R A, Hewick R M, Kaufman R J, Mann K G. PubMed
Variant Summaries rs6025
Drugs
Diseases

Appendix

Gene Common Namecoagulation factor V, proaccelerin, labile factor
No related genes are available

Curated Information ?

Curated Information ?

Publications related to F5: 20

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic polymorphisms of pharmacogenomic VIP variants in Li nationality of southern China. Environmental toxicology and pharmacology. 2016. Ding Yipeng, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Hypertension pharmacogenomics: in search of personalized treatment approaches. Nature reviews. Nephrology. 2015. Cooper-DeHoff Rhonda M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic polymorphisms of pharmacogenomic VIP variants in the lhoba population of southwest China. International journal of clinical and experimental pathology. 2015. He Yongjun, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A pharmacogenetics-based warfarin maintenance dosing algorithm from northern chinese patients. PloS one. 2014. Chen Jinxing, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Integrating EMR-Linked and In Vivo Functional Genetic Data to Identify New Genotype-Phenotype Associations. PloS one. 2014. Mosley Jonathan D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomic Association of Nonsynonymous SNPs in SIGLEC12, A1BG, and the Selectin Region and Cardiovascular Outcomes. Hypertension. 2013. McDonough Caitrin W, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of antiangiogenic and antineovascular therapies of age-related macular degeneration. Pharmacogenomics. 2012. Agosta Elisa, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Genetic and environmental factors determining clinical outcomes and cost of warfarin therapy: a prospective study. Pharmacogenetics and genomics. 2009. Jorgensen Andrea L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The effect of nine common polymorphisms in coagulation factor genes (F2, F5, F7, F12 and F13 ) on the effectiveness of statins: the GenHAT study. Pharmacogenetics and genomics. 2009. Maitland-van der Zee Anke-Hilse, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Predictive role of coagulation-balance gene polymorphisms in the efficacy of photodynamic therapy with verteporfin for classic choroidal neovascularization secondary to age-related macular degeneration. Pharmacogenetics and genomics. 2007. Parmeggiani Francesco, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Oral contraceptive use, thrombophilia and their interaction in young women with ischemic stroke. Haematologica. 2006. Martinelli Ida, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Prothrombotic conditions, oral contraceptives, and the risk of ischemic stroke. Journal of thrombosis and haemostasis : JTH. 2005. Slooter A J C, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Venous thromboembolic disease in users of low-estrogen combined estrogen-progestin oral contraceptives. Contraception. 2004. Sidney Stephen, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effect of factor V Leiden polymorphism in severe sepsis and on treatment with recombinant human activated protein C. Critical care medicine. 2004. Yan S Betty, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Venous thromboembolism in young women; role of thrombophilic mutations and oral contraceptive use. European heart journal. 2002. Legnani C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interaction of fibrinolysis and prothrombotic risk factors in neonates, infants and children with and without thromboembolism and underlying cardiac disease. a prospective study. Thrombosis research. 2001. Nowak-Göttl U, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arteriosclerosis, thrombosis, and vascular biology. 1999. Martinelli I, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Oral contraceptives enhance the risk of clinical manifestation of venous thrombosis at a young age in females homozygous for factor V Leiden. British journal of haematology. 1996. Rintelen C, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet. 1994. Vandenbroucke J P, et al. PubMed

LinkOuts

NCBI Gene:
2153
OMIM:
188055
227400
600880
601367
612309
UCSC Genome Browser:
NM_000130
RefSeq RNA:
NM_000130
RefSeq Protein:
NP_000121
RefSeq DNA:
NG_011806
NT_004487
UniProtKB:
FA5_HUMAN (P12259)
Ensembl:
ENSG00000198734
GenAtlas:
F5
GeneCard:
F5
MutDB:
F5
ALFRED:
LO000606M
HuGE:
F5
Comparative Toxicogenomics Database:
2153
ModBase:
P12259
HGNC:
3542

Common Searches