Coagulation Factor V

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OMIM Number

612309

NCBI Gene ID

2153

Uniprot ID

P12259

Length

74635 bases

No. of Exons

25

No. of isoforms

1

Protein Name

Coagulation factor V

Molecular Mass

251703Da

Amino Acid Count

2224

Genomic Location

chr1:169511954-169586588

Gene Map Locus
1q24.2

Description

The F5 gene encodes coagulation factor V, which is an essential cofactor of the blood coagulation cascade. Factor V is primarily synthesized in the liver and it's inactive form circulates in plasma until the coagulation system is activated by an injury that damages blood vessels. When converted into the active form (called factor Va), it interacts with activated coagulation factor X (factor Xa) to convert prothrombin to thrombin. Thrombin then converts fibrinogen into fibrin, which forms a mesh by binding together and stabilizes the platelet plug at the injury site. Coagulation factor V also has another role in regulating the coagulation system through its interaction with activated protein C (APC). APC normally inactivates coagulation factor V by cleaving it at specific sites. This inactivation slows down the clotting process and prevents the development of an abnormal blood clot. When coagulation factor V is cleaved at a particular site (protein position 506), it can work with APC to inactivate factor VIIIa, which is another protein that is essential for normal blood clotting.

Molecular Genetics

The F5 gene is the only gene associated with factor V Leiden thrombophilia. This disease is caused by specific mutation (Arg506Gln) known as the factor V Leiden mutation. As position 506 is one of the sites where APC normally cleaves coagulation factor V, the factor V Leiden mutation slows the rate at which APC inactivates this factor. As a result, both the activated form of coagulation factor V and coagulation factor VIIIa persist longer in circulation, increasing the risk of developing an abnormal blood clot (thrombosis). Additionally, other mutations in this gene are responsible for factor V deficiency (FA5D), also known as Owren parahemophilia, which is an autosomal recessive hemorrhagic diathesis. Furthermore, mutations in F5 are a cause of susceptibility to Budd-Chiari syndrome (BCS), and ischemic stroke.

Epidemiology in the Arab World

View Map
Variant NameCountryGenomic LocationClinical SignificanceCondition(s)HGVS ExpressionsdbSNPClinvar
NM_000130.4:c.1601G>ALebanonNC_000001.11:g.169549811C>TBenign,Pathogenic,Risk factorThrombophilia due to thrombin defect; Stroke, Ischemic; Pregnancy Loss, Recurrent, Susceptibility to, 1; Pregnancy Loss, Recurrent, Susceptibility to, 2 ; Thrombophilia due to Activated Protein C ResistanceNG_011806.1:g.41721G>A; NM_000130.4:c.1601G>A; NP_000121.2:p.Arg534Gln6025642
NM_000130.4:c.3980A>GLebanonNC_000001.11:g.169541110T>CBenign,Likely BenignStroke, Ischemic; Thrombophilia due to Activated Protein C ResistanceNG_011806.1:g.50422A>G; NM_000130.4:c.3980A>G; NP_000121.2:p.His1327Arg180059537345

Other Reports

Egypt

[See: Kuwait > Dashti et al., 2010].

Jordan

[See: Kuwait > Dashti et al., 2010].

Kuwait

Jadaon et al. (2006) conducted a molecular study to report a point mutation in the clotting factor V gene. Two hundred and eighty-eight subjects, 188 patients with venous thromboembolic disorders (VTE) and 100 age- and sex-matched healthy individuals, all of Arab ethnicity and living in Kuwait, were tested for the HR2 haplotype. The presence of the mutation was verified by DNA sequencing. Two (1.06%) VTE patients were found to have guanine instead of the wild-type adenine at nucleotide number 3935 (c.A3935G) of the factor V gene. This mutation caused a histidine to arginine change in amino acid number 1254 of the factor V molecule (p.His1254Arg). This mutation, termed 'factor V Kuwait', was absent in the 100 healthy subjects. Jadaon et al. (2006) concluded that factor V Kuwait could be a risk factor for developing VTE in Arabs, and a larger study is needed to confirm this observation. Jadaon et al. (2006) thought that the mutation which they identified in this study is new mutation, but it had been previously reported in Somali patients [See: Somalia > Lunghi et al., 1998].

Elshafaay et al. (2008) studied 1000 couples with a history of Recurrent Pregnancy Loss (RPL). Cytogenetic studies identified only 44 patients with chromosomal abnormalities. Of the remaining patients, a sub-group of 100 female patients were tested for the presence of factor V Leiden mutation. The results showed that the prevalence of Factor V Leiden was significantly higher (10% vs. 2%) in the patients than in the control cases (100 females without any history of RPL). Elshafaay et al. (2008) suggested that women with RPL, especially those that show a normal karyotype, be tested for markers of thrombophilia.

Dashti et al. (2010) used real time PCR to study the Factor V Leiden mutation among 400 healthy Arabs (200 males, 200 females) in Kuwait. Two-thirds of these subjects were Kuwaitis. The non-Kuwaiti Arab subjects included 50 Syrians, 40 Egyptians, 34 Jordanians, and eight Palestinians. Overall, 36 subjects (9%) were found to carry the FVL mutation, giving an allelic frequency of 0.049. The allelic frequency among the non-Kuwaitis was calculated at 0.088 for Egyptians, 0.090 for Syrians, 0.125 for Palestinians, and 0.132 for Jordanians. The prevalence of FVL in Kuwaitis at 4.5% was significantly lesser than that in non-Kuwaiti Arabs (15-25%). The Kuwaiti prevalence was similar to that reported from other countries of the Arabian Gulf, while the prevalence among the Syrians, Jordanians, Palestinians, and Egyptians was similar to that reported from previous studies on Eastern Mediterranean countries.

Palestine

[See: Kuwait > Dashti et al., 2010].

Saudi Arabia

Mammo et al. (2007) reported the incidences of five prothrombotic gene polymorphisms among Saudi Arabians. The data for this study came from the Saudi Thrombosis and Familial Thrombophilia Registry. The subjects were healthy consenting donors from different regions, tribes, and origins in Saudi Arabia. Between 2001 and 2005, DNA samples from 902 Saudis (793 men and 109 women) were collected and genotyped. The Factor V Leiden mutation was tested in 902 of these subjects. Heterozygous carrier rate for this mutation was found to be 1.22%, while 0.11% of the subjects were homozygous rare allele carriers. The incidence of the rare allele was 1.3% (frequency: 0.72%). On the other hand, 642 subjects were tested for the HR2 mutation in this gene. The heterozygous carrier rate for this mutation was found to be 22%, while the rare allele incidence was 24%.

Awad and El-Tarras (2012) studied two hundred blood samples collected from healthy Saudis residing in Taif.  Factor V H1299R polymorphism was detected in some of the patients.  Of these, 14 individuals were shown to be heterozygous, while three were confirmed to be homozygous for the polymorphism.  This study indicated that the prevalence of HR2 haplotype in the Saudi population was 8.5% and the allelic frequencies of A and G alleles were 0.95 and 0.05, respectively.

Somalia

Bernardi et al. (1997) investigated factor V gene polymorphisms to detect components that may contribute to the activated protein C (APC) resistance phenotype in patients with venous thromboembolism. A specific factor V gene haplotype (HR2) was defined by six polymorphisms and its frequency was found to be similar in normal subjects coming from Italy (0.08), India (0.1), and Somalia (0.08), indicating that it was originated by ancestral mutational events. The HR2 haplotype was significantly more frequent in patients with ratios below the 15th percentile than in those with higher ratios or in normal controls. The HR2 haplotype was associated with significantly lower APC ratios both in patients with venous thromboembolism and in age- and sex-matched controls. However, the two groups showed similar HR2 haplotype frequencies. Later, Lunghi et al. (1998) found a new factor V gene polymorphism (c.A3935G; R3 polymorphism), causing the incorporation of an Arg in the place of His1254 (CAT/CGT; p.His1254Arg). Six out of 40 Somali in the studied sample were found to have this new polymorphism in the heterozygous condition (frequency of the G allele 0.075).

Syria

[See: Kuwait > Dashti et al., 2010].

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