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F5

coagulation factor V

The F5 gene provides instructions for coagulation factor V, a protein that plays a central role in the body's blood clotting system. Coagulation factor V is essential for forming blood clots, which stop bleeding after injury and initiate vessel repair.

Chromosome 1q24.2 Autosomal dominant HGNC:3542 Tier C
F5 1q24.2 p arm q arm 1

F5 is located on the long (q) arm of chromosome 1, at band 1q24.2. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 1 in the library →

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Clinical tests that include this

Carrier Screening panel
F5 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The F5 gene encodes coagulation factor V, a crucial protein within the coagulation cascade, the complex series of steps that leads to blood clot formation. This protein is vital for haemostasis, the process that prevents and stops bleeding. Defects or alterations in the F5 gene can disrupt this delicate balance, resulting in various clinical implications, from increased risk of blood clots to bleeding tendencies.

What the gene does

The F5 gene provides instructions for synthesising coagulation factor V, a protein primarily produced by liver cells. This protein circulates in the bloodstream in an inactive state until the coagulation system is triggered, typically by an injury that damages blood vessels. Once activated, factor V (now denoted as factor Va) interacts with activated coagulation factor X (factor Xa) to form a complex. This complex is instrumental in converting prothrombin into its active form, thrombin, which then facilitates the conversion of fibrinogen into fibrin, the structural component of a blood clot. Coagulation factor V also plays a regulatory role by interacting with activated protein C (APC), which normally inactivates factor V to prevent excessive clotting. This inactivation process helps to control the size and dissolution of blood clots.

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Chromosome location

The F5 gene is located on chromosome 1 at position 1q24.2. This genomic location specifies the precise region on the long arm (q arm) of chromosome 1 where the gene resides.

Protein structure

The coagulation factor V protein, with a length of 2224 amino acids, exhibits a modular structure. It contains two F5/8 type A domains: F5/8 type A 1 (amino acids 30-329) and F5/8 type A 2 (amino acids 348-684). Within the first F5/8 type A domain are Plastocyanin-like 1 (amino acids 30-193) and Plastocyanin-like 2 (amino acids 203-329). The second F5/8 type A domain incorporates Plastocyanin-like 3 (amino acids 348-526) and Plastocyanin-like 4 (amino acids 536-684). A large B Region is found between amino acids 692-1573, which includes several disordered regions (amino acids 822-842, 894-927, 982-1001, 1029-1048, and 1097-1157). Within the B Region, there are also 2 X 17 AA tandem repeats (amino acids 895-928), specifically 1-1 (amino acids 895-911) and 1-2 (amino acids 912-928).

Domain map · 2,224 amino acids
F5/8 type A 1 (30–329)Plastocyanin-like 1 (30–193)F5/8 type A 2 (348–684)Plastocyanin-like 3 (348–526)F5/8 type A 3 (1578–1907)Plastocyanin-like 5 (1578–1751)F5/8 type C 1 (1907–2061)F5/8 type C 2 (2066–2221)F5/8 type A 130–329F5/8 type A 2348–684F5/8 type A 31578–19071~1,1122,224
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:P12259Length:2,224 aaStructure:AlphaFold

Key variants

Variants within the F5 gene can significantly impact the structure and function of coagulation factor V. These genetic changes may alter the protein's ability to participate effectively in the blood clotting cascade, leading to either an increased propensity for clotting or an impaired ability to form clots. The clinical consequences depend on the specific variant and its effect on protein activity.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for F5.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1258G>T
single nucleotide variant
 p.Gly420Cys Pathogenic ★★☆☆ Congenital factor V deficiency
c.2021del
Deletion
 p.Lys674fs Pathogenic/Likely pathogenic ★★☆☆ Congenital factor V deficiency
c.2539del
Deletion
 p.Ile847fs Pathogenic/Likely pathogenic ★★☆☆ Congenital factor V deficiency
c.286G>C
single nucleotide variant
 p.Asp96His Pathogenic ★★☆☆ Congenital factor V deficiency
c.3088C>T
single nucleotide variant
 p.Arg1030Ter Pathogenic ★★☆☆ Congenital factor V deficiency
c.3799del
Deletion
 p.Leu1267fs Pathogenic/Likely pathogenic ★★☆☆ Pregnancy loss, recurrent, susceptibility to, 1
c.436C>T
single nucleotide variant
 p.Arg146Ter Pathogenic/Likely pathogenic ★★☆☆ Congenital factor V deficiency
c.4861C>T
single nucleotide variant
 p.Arg1621Ter Pathogenic/Likely pathogenic ★★☆☆ Congenital factor V deficiency
c.4900C>T
single nucleotide variant
 p.Arg1634Ter Pathogenic/Likely pathogenic ★★☆☆ Congenital factor V deficiency
c.5453del
Deletion
 p.Leu1818fs Pathogenic/Likely pathogenic ★★☆☆ Congenital factor V deficiency

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Variants in the F5 gene are associated with conditions that affect blood clotting. One notable condition is Factor V Leiden, which is linked to an increased risk of venous thromboembolism. Other variants can lead to Factor V deficiency, a rare bleeding disorder. These conditions highlight the gene's critical role in maintaining the balance of the coagulation system.

  • Factor V Leiden
    Haematology
    AD
  • Factor V Leiden (heterozygous)
    Haematology
    AD
    Dedicated page coming soon
  • Venous thromboembolism
    Haematology
    Polygenic / Complex
    Dedicated page coming soon

Inheritance pattern

Conditions caused by pathogenic F5 variants typically follow autosomal dominant inheritance.

♀ Affected parent 1 altered copy ♂ Unaffected parent 2 typical copies Affected Unaffected Unaffected Affected Affected Carrier Unaffected Circles = females · Squares = males

Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.

Carrier frequency by population How common is heterozygous F5 carrier status across ancestry groups?

UK clinical status

The F5 gene is included in several NHS Genomic Medicine Service national test panels. These include panels for "Bleeding and platelet disorders," "Factor V deficiency," "Inherited bleeding disorders," and "Thrombophilia with a likely monogenic cause," indicating its clinical relevance within the UK healthcare system.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Bleeding and platelet disorders · R90 NHS GMS → Factor V deficiency · R115 NHS GMS → Thrombophilia with a likely monogenic cause · R97 NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the F5 gene?

The F5 gene provides instructions for making coagulation factor V, a protein that is crucial for the formation of blood clots. It acts as a cofactor in the coagulation cascade, helping to convert prothrombin into thrombin, which then leads to fibrin formation.

What happens if there is a variant in the F5 gene?

Variants in the F5 gene can either increase or decrease the blood's tendency to clot. For example, the Factor V Leiden variant is associated with an increased risk of blood clots, while other variants can lead to Factor V deficiency, a condition characterised by excessive bleeding.

Is Factor V Leiden a common condition?

Factor V Leiden is one of the most common inherited causes of thrombophilia, a disorder that increases the risk of abnormal blood clots. Its prevalence varies across different populations, with higher rates observed in individuals of European descent.

References

  1. Cutler JA, Patel R, Rangarajan S. Molecular characterization of 11 novel mutations in patients with heterozygous and homozygous FV deficiency. Haemophilia : the official journal of the World Federation of Hemophilia. 2010. PMID: 20546033
  2. Asselta R, Peyvandi F. Factor V deficiency. Seminars in thrombosis and hemostasis. 2009. PMID: 19598066
  3. Rosendorff A, Dorfman DM. Activated protein C resistance and factor V Leiden: a review. Archives of pathology & laboratory medicine. 2007. PMID: 17550313
  4. Segers K, Dahlbäck B, Nicolaes GA. Coagulation factor V and thrombophilia: background and mechanisms. Thrombosis and haemostasis. 2007. PMID: 17849041
  5. Vos HL. Inherited defects of coagulation Factor V: the thrombotic side. Journal of thrombosis and haemostasis : JTH. 2006. PMID: 16246256
  6. Asselta R, Tenchini ML, Duga S. Inherited defects of coagulation factor V: the hemorrhagic side. Journal of thrombosis and haemostasis : JTH. 2006. PMID: 16409445
  7. Colak Y, Karasu Z, Oruc N. Hyperhomocysteinaemia and factor V Leiden mutation are associated with Budd-Chiari syndrome. European journal of gastroenterology & hepatology. 2006. PMID: 16825912
  8. Brugge JM, Simioni P, Bernardi F. 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. PMID: 16359508
  9. Duga S, Asselta R, Tenchini ML. Coagulation factor V. The international journal of biochemistry & cell biology. 2004. PMID: 15147718
  10. Castoldi E, Rosing J. Factor V Leiden: a disorder of factor V anticoagulant function. Current opinion in hematology. 2004. PMID: 15257017
  11. Mann KG, Kalafatis M. Factor V: a combination of Dr Jekyll and Mr Hyde. Blood. 2003. PMID: 12393635
  12. Ornstein DL, Cushman M. Cardiology patient page. Factor V Leiden. Circulation. 2003. PMID: 12707252
  13. Nicolaes GA, Dahlbäck B. Factor V and thrombotic disease: description of a janus-faced protein. Arteriosclerosis, thrombosis, and vascular biology. 2002. PMID: 11950687
  14. Grody WW, Griffin JH, Taylor AK. American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Genetics in medicine : official journal of the American College of Medical Genetics. 2001. PMID: 11280951
  15. Janssen HL, Meinardi JR, Vleggaar FP. Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study. Blood. 2000. PMID: 11001884
  16. Lak M, Sharifian R, Peyvandi F. Symptoms of inherited factor V deficiency in 35 Iranian patients. British journal of haematology. 1998. PMID: 9886321
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 27 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .