{{Rsnum
|rsid=6025
|Gene=F5
|Chromosome=1
|position=169549811
|Orientation=minus
|ReferenceAllele=G
|MissenseAllele=A
|GMAF=0.005969
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=F5
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 0.9 | 2.7 | 96.5
| HCB | 0.0 | 0.7 | 99.3
| JPT | 0.0 | 0.0 | 100.0
| YRI | 0.0 | 0.0 | 100.0
| ASW | 0.0 | 0.0 | 0.0
| CHB | 0.0 | 0.7 | 99.3
| CHD | 0.0 | 0.9 | 99.1
| GIH | 0.0 | 1.0 | 99.0
| LWK | 0.0 | 0.9 | 99.1
| MEX | 0.0 | 3.4 | 96.6
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 1.0 | 99.0
| HapMapRevision=28
}}

[[rs6025]] represents a SNP in the Factor V [[F5]] gene, encoding a change in the protein from an arginine at position 506 to a glutamine. The resulting [[rs6025]](A) allele encodes a mutation known as the Leiden mutation, R506Q, found in perhaps 3 to 5% of the individuals in most populations. About 1 in 10 individuals harboring the R506Q will experience clinically significant [[venous thromboembolism]] in their lifetimes (according to [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227400 OMIM]).

Overall, the [[rs6025]](A) allele appears to be necessary but not sufficient for the development of [[venous thromboembolism]]. Patients who are [[rs6025]](A;G) heterozygotes but lack other risk-enhancing SNPs have a risk of recurrent deep venous thrombosis equal to patients with no such SNPs. In contrast, patients who are heterozygotes for both [[rs6025]] and the prothrombin [[rs1799963]] SNP have a higher risk of recurrent thrombosis (relative risk, 2.6, CI: 1.3 to 5.1, p=0.002), and depending on other factors, this risk can climb to at least 5x. One study concludes that heterozygotes for [[rs6025]] and [[rs1799963]] have an increased risk of recurrent deep venous thrombosis after a first episode and are therefore candidates for lifelong anticoagulation treatment.
{{PMID|10477778}}

More recent (and larger) studies have come to similar conclusions. In a study of over 9,000 Caucasian adults, [[rs6025]](A;G) and [[rs6025]](A;A) genotypes had 2.7x and 18x higher risk for [[venous thromboembolism]], respectively, than [[rs6025]](G;G) individuals. The lowest absolute 10-year risks for [[venous thromboembolism]] for (A;G) and (A;A) genotypes are 0.7% (CI: 0.5% to 1.0%) and 3% (CI: 1% to 8%) for nonsmokers younger than 40 years of age with a body mass index below 25 kg/m2, and the corresponding highest risks were 10% (CI: 7% to 14%) and 51% (CI: 13% to 100%) for overweight smokers over 60.{{PMID|14996674}}

Women who are pregnant and [[rs6025]](A) carriers may be at risk for obstetric complications, including [[pre-eclampsia]] or [[venous thromboembolism]], especially if they are also prothrombin [[rs1799963]] heterozygotes and/or have a family history of thrombosis. One study concludes that if you assume an overall risk rate of 1 in 1500 pregnancies, the risk of thrombosis among [[rs6025]](A)  carriers by itself is 0.2 percent (1 in 500); among carriers of the prothrombin [[rs1799963]](A) by itself, 0.5 percent (1 in 200); and among carriers of both variant SNPs, 4.6 percent (about 1 in 20).{{PMID|10666427}}

Women who are [[rs6025]](A) carriers also are at increased risk for [[venous thromboembolism]] and perhaps ischemic stroke when they take combined oral contraceptives (i.e. "the pill"). A 2006 literature meta-analysis from a total of 10 studies concluded that "good" evidence existed for a greater risk of [[venous thromboembolism]] (risk ratios of 1.3-25.1) and cerebral vein or cerebral sinus thrombosis when comparing heterozygotes taking such contraceptives to heterozygotes who did not.{{PMID|16413847}} 

Additionally, an increased risk for ischemic [[stroke]] has been found for [[rs6025]](A) carriers. The odds ratio based on a study of ~4,500 patients is 1.33, CI: 1.12-1.58.{{PMID|15534175}}

Although preliminary, a 2010 study found that women taking [[tamoxifen]] as part of their treatment for early-stage [[breast cancer]], those who had a thromboembolic event were nearly five times more likely to have a [[rs6025]](A) allele compared to those who did not have a TE. The authors suggest that postmenopausal women should be evaluated for the [[rs6025]](A) SNP before being given a prescription for [[tamoxifen]] if the result would affect the decision.{{PMID|20554945|OA=1
}} A related editorial points out that [[tamoxifen]] on its own is known to increase the risk of thromboembolic events 2-4 fold.{{PMID|20554943}}

{{Venter SNP
|rsid=6025
|allele=C
|frequency=0.992
|uid=1103675256965
|type=homozygous_SNP
|hugo=F5
|ensembl gene=ENSG00000198734
|ensembl transcript=ENST00000367796
|sift=TOLERATED
|disease=Defects in F5 are the cause of resistance to activated protein C (APCR) (MIM:188055). APCR is a form of thrombophilia. The APCR mutation is found in about 5% of the population which suggest that a slight thrombotic tendency may confer some advantage in fetal implantation.
}}

{{PMID Auto
|PMID=19415820
|Title=The effect of nine common polymorphisms in coagulation factor genes (F2, F5, F7, F12 and F13 ) on the effectiveness of statins: the GenHAT study
|OA=1
}}

{{PMID Auto
|PMID=19786296
|Title=Platelet glycoprotein GP VI 13254C allele is an independent risk factor of premature myocardial infarction
}}

{{PharmGKB
|RSID=rs6025
|Name_s=F5:Factor V Leiden (FVL)
|Gene_s=F5
|Feature=
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/f5/variant.jsp
|Annotation=Associated with risk of venous thromboembolism (VTE).
|Drugs=drotrecogin alfa; tamoxifen
|Drug Classes=ESTROGENS; HORMONAL CONTRACEPTIVES FOR SYSTEMIC USE
|Diseases=Thromboembolism; venous thromboembolism
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161145169
}}

{{PMID Auto
|PMID=21291465
|Title=The association of genetic polymorphisms with cerebral palsy: a meta-analysis
}}

{{omim
|id=612309
|rsnum=6025
|variant=0001
}}

{{PMID Auto
|PMID=21564075
|Title=Resistance to activated protein C is a risk factor for pregnancy-related venous thrombosis in the absence of the F5 rs6025 (factor V Leiden) polymorphism
}}

{{PMID Auto
|PMID=21332313
|Title=Sequence variations in the FII, FV, F13A1, FGB and PAI-1 genes are associated with differences in myocardial perfusion
}}

{{PMID Auto
|PMID=21659962
|Title=Replication of genetic associations in the inflammation, complement, and coagulation pathways with intraventricular hemorrhage in LBW preterm neonates
|OA=1
}}

{{PMID Auto
|PMID=22198364
|Title=The association of inherited thrombophilia and intrauterine fetal death:  a case-control study
}}

{{PMID Auto
|PMID=21913742
|Title=Genetic predictors of response to photodynamictherapy
}}

{{PMID Auto
|PMID=21955043
|Title=Validation of single nucleotide polymorphisms associated with acute rejection in kidney transplant recipients using a large multi-center cohort
|OA=1
}}

{{PMID Auto
|PMID=22421107
|Title=The G534E-polymorphism of the gene encoding the Factor VII-activating protease is a risk factor for venous thrombosis and recurrent events
}}

{{PMID Auto
|PMID=22707612
|Title=Genetic Risk Factors for Thrombosis in Systemic Lupus Erythematosus
|OA=1
}}

{{ClinVar
|rsid=6025
|Reversed=1
|FwdREF=G
|FwdALT=A
|REF=C
|ALT=T
|RSPOS=169549811
|CHROM=1
|GMAF=0.006
|dbSNPBuildID=52
|SSR=0
|SAO=1
|VP=0x05016800000504051f130101
|WGT=1
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000001.11:g.169549811C>T
|CLNSRC=ClinVar; GTR; OMIM Allelic Variant
|CLNORIGIN=1
|CLNSRCID=NM_000130.4:c.1601G>A; GTR000115631; GTR000204879; GTR000219927; GTR000325434; GTR000500304; GTR000502757; GTR000509324; GTR000509357; GTR000509358; GTR000512436; 612309.0001
|CLNSIG=255
|CLNCUI=C0000809
|CLNDBN=Thrombophilia due to factor V Leiden; Ischemic stroke, susceptibility to; Budd-Chiari syndrome, susceptibility to; Recurrent abortion
|Disease=Thrombophilia due to factor V Leiden; Ischemic stroke; Budd-Chiari syndrome; Recurrent abortion
|CLNACC=RCV000000674.1; RCV000000675.1; RCV000000676.1; RCV000023935.1
|Tags=RV;PM;PMC;SLO;ASP;VLD;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;MTP;OM
|CAF=0.005969; 0.994
|CLNDSDB=MedGen; MedGen:OMIM:SNOMED_CT
|CLNDSDBID=C2674152; C0000809:614389:102878001
|COMMON=1
|GENEINFO=F5:2153
|GENE_ID=2153
|GENE_NAME=F5
}}

{{PMID|16846490|OA=1
}} Lemierre's syndrome and genetic polymorphisms: a case report.

{{PMID|17048007|OA=1
}} Association of warfarin dose with genes involved in its action and metabolism.

{{PMID|17107626|OA=1
}} Comparison of PrASE and Pyrosequencing for SNP Genotyping.

{{PMID|17677000|OA=1
}} Combined effects of thrombosis pathway gene variants predict cardiovascular events.

{{PMID|18513389|OA=1
}} New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.

{{PMID|18752569}} Factor V Leiden is associated with pre-eclampsia but not with fetal growth restriction: a genetic association study and meta-analysis.

{{PMID|18936436|OA=1
}} Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.

{{PMID|19131662|OA=1
}} A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.

{{PMID|19263529|OA=1
}} Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.

{{PMID|19330901|OA=1
}} Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.

{{PMID|19536175|OA=1
}} Follow-up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study.

{{PMID|19538716|OA=1
}} Thrombotic genetic risk factors and warfarin pharmacogenetic variants in Sao Miguel's healthy population (Azores).

{{PMID|19559392|OA=1
}} A candidate gene association study of 77 polymorphisms in migraine.

{{PMID|19591822}} Prevalence of genetic thrombophilic polymorphisms in the Sri Lankan population--implications for association study design and clinical genetic testing services.

{{PMID|20031567|OA=1
}} An evaluation of candidate genes of inflammation and thrombosis in relation to the risk of venous thromboembolism: The Women's Genome Health Study.

{{PMID|20352152}} Association of common genetic variations and idiopathic venous thromboembolism. Results from EDITh, a hospital-based case-control study.

{{PMID|21422408}} Clotting factor gene polymorphisms and colorectal cancer risk.

{{PMID|22388798|OA=1
}} Gene panels to help identify subgroups at high and low risk of coronary heart disease among those randomized to antihypertensive treatment: the GenHAT study.

{{PMID|22540831}} Candidate gene study of genetic thrombophilic polymorphisms in pre-eclampsia and recurrent pregnancy loss in Sinhalese women.

{{PMID Auto GWAS
|PMID=22672568
|Trait=None
|Title=A genome-wide association study of venous thromboembolism identifies risk variants in chromosomes 1q24.2 and 9q.
|RiskAllele=T
|Pval=2E-22
|OR=3.5700
|ORtxt=None
|OA=1
}}

{{PMID Auto
|PMID=23015030
|Title=Differential haemostatic risk factors for pregnancy related deep vein thrombosis and pulmonary embolism. A population-based case-control study
}}

{{PMID Auto
|PMID=23018527
|Title=Necessity and risks of arterial blood sampling in healthy volunteer studies
}}

{{GET Evidence
|gene=F5
|aa_change=Gln534Arg
|aa_change_short=Q534R
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs6025
|overall_frequency_n=10522
|overall_frequency_d=10758
|overall_frequency=0.978063
|n_genomes=56
|n_genomes_annotated=0
|n_haplomes=110
|n_articles=0
|n_articles_annotated=0
|qualityscore_in_silico=2
|qualitycomment_in_silico=Y
|gene_in_genetests=Y
|in_pharmgkb=Y
|genetests_testable=Y
|genetests_reviewed=Y
|nblosum100=0
|autoscore=4
|webscore=N
|n_web_uneval=1
}}

{{PMID Auto
|PMID=23132613
|Title=Genetic association studies in pre-eclampsia: systematic meta-analyses and field synopsis
}}

{{PMID Auto
|PMID=23150947
|Title=Single nucleotide polymorphisms and the risk of venous thrombosis: results from a Danish case-cohort study
}}

[[Placental Abruption]]

[[Oral Contraceptives, HRT and Risk of VTE]]

{{PMID Auto
|PMID=23274712
|Title=Genetic polymorphisms and the risk of myocardial infarction in patients under 45 years of age.
|OA=1
}}

{{PMID Auto
|PMID=23533563
|Title=Novel risk factors for premature peripheral arterial occlusive disease in non-diabetic patients: a case-control study.
|OA=1
}}

{{PMID Auto
|PMID=24908450
|Title=A genetic association study of D-dimer levels with 50K SNPs from a candidate gene chip in four ethnic groups
}}

{{PMID Auto
|PMID=25028703
|Title=Maternal Genotype and Severe Preeclampsia: A HuGE Review
}}

{{PMID Auto
|PMID=25119470
|Title=Single Nucleotide Polymorphisms Other than Factor V Leiden Are Associated with Coagulopathy and Osteonecrosis of the Femoral Head in Chinese Patients
}}

{{PMID Auto
|PMID=25210051
|Title=Genetic Variations Associated with Recurrent Venous Thrombosis
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | FTDNA}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}