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F7
coagulation factor VII
The F7 gene provides instructions for producing coagulation factor VII, a vital protein that plays a central role in the blood clotting cascade, essential for stopping bleeding after injury. F7 is a gene critical for haemostasis, the process that prevents and stops bleeding.
F7 is located on the long (q) arm of chromosome 13, at band 13q34. Arm ratio per GRCh38 - banding schematic.
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Overview
The F7 gene is responsible for creating coagulation factor VII, a protein integral to the complex process of blood clotting. This protein is a key component of the coagulation system, a series of biochemical reactions designed to seal damaged blood vessels and facilitate repair. Factor VII is produced mainly by liver cells and exists in an inactive form until an injury triggers its activation, setting off a cascade of events that leads to the formation of a stable blood clot.
What the gene does
Coagulation factor VII, encoded by the F7 gene, is a serine protease that initiates the extrinsic pathway of blood coagulation. Once activated, Factor VIIa (the activated form) forms a complex with tissue factor at the site of vascular injury. This complex then activates factor X and factor IX, leading to the generation of thrombin. Thrombin, in turn, converts fibrinogen into fibrin, which polymerises to form the structural meshwork of a blood clot. This precise, step-wise activation ensures that blood clotting occurs only when and where it is needed, preventing excessive bleeding while avoiding inappropriate clot formation.
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Chromosome location
The F7 gene is located on chromosome 13, specifically at position 13q34. This means it is found on the long arm (q) of chromosome 13, within band 34. The gene's precise location helps in understanding its genetic neighbourhood and potential interactions with other genes.
Protein structure
The coagulation factor VII protein is composed of 466 amino acids and features several distinct functional regions. It contains a Gla (Gamma-carboxyglutamic acid) domain, located from amino acids 61-105, which is crucial for calcium-dependent binding to phospholipid surfaces. Following this are two EGF-like domains: EGF-like 1; calcium-binding (amino acids 106-142) and EGF-like 2 (amino acids 147-188). The protein also includes a large Peptidase S1 domain, spanning amino acids 213-452, which contains the catalytic site responsible for its protease activity.
Key variants
Genetic variations within the F7 gene can alter the production or function of coagulation factor VII. These variants, which may include missense changes, deletions, or insertions, can affect the protein's stability, its ability to become activated, or its enzymatic activity within the clotting cascade. The specific impact of a variant often depends on its location within the gene and how it alters the protein's structure or function.
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.1318C>T | p.Arg440Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital factor VII deficiency |
c.154dup | p.Glu52fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital factor VII deficiency |
c.178T>C | p.Cys60Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Factor VII deficiency |
c.225+1G>C | - | Pathogenic | ★★☆☆ | Congenital factor VII deficiency |
c.2T>C | p.Met1Thr | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.505+78G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital factor VII deficiency |
c.517T>C | p.Cys173Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital factor VII deficiency |
c.568C>T | p.Arg190Ter | Pathogenic | ★★☆☆ | Congenital factor VII deficiency |
c.581del | p.Gly194fs | Pathogenic | ★★☆☆ | F7-related disorder |
c.64G>A | p.Val22Ile | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital factor VII 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
Pathogenic variants in the F7 gene are primarily associated with an inherited bleeding disorder known as Factor VII deficiency. This condition is inherited in an autosomal recessive pattern, meaning an individual must inherit two copies of a pathogenic variant (one from each parent) to be affected. Individuals with Factor VII deficiency may experience symptoms ranging from mild, such as easy bruising and nosebleeds, to severe, including life-threatening internal haemorrhages.
Inheritance pattern
Conditions caused by pathogenic F7 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The F7 gene is included in several UK NHS national genomic testing panels, reflecting its established clinical significance. It is listed on the 'Bleeding and platelet disorders' panel (R90), the 'Factor VII deficiency' panel (R116), and the 'Inherited bleeding disorders' panel. Its presence on these panels indicates that variants in F7 are considered in the diagnosis and management of inherited bleeding conditions within the NHS Genomic Medicine Service.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the F7 gene responsible for?
The F7 gene provides instructions for making coagulation factor VII, a protein essential for blood clotting. This protein helps to initiate the formation of blood clots, which are crucial for stopping bleeding after an injury.
How is Factor VII deficiency inherited?
Factor VII deficiency is inherited in an autosomal recessive pattern. This means that an individual must inherit two altered copies of the F7 gene, one from each parent, to develop the condition. Individuals with only one altered copy are typically carriers and usually do not show symptoms.
What are common symptoms of Factor VII deficiency?
Common symptoms of Factor VII deficiency can include easy bruising, frequent nosebleeds, gum bleeding, and prolonged or excessive bleeding after surgery or injury. In more severe cases, individuals may experience dangerous internal bleeding episodes.
References
- Girolami A, Cosi E, Santarossa C. The Story of Serum Prothrombin Conversion Accelerator, Proconvertin, Stable Factor, Cothromboplastin, Prothrombin Accelerator or Autoprothrombin I, and Their Subsequent Merging into Factor VII. Seminars in thrombosis and hemostasis. 2015. PMID: 25973586
- Herrmann FH, Wulff K, Auerswald G. Factor VII deficiency: clinical manifestation of 717 subjects from Europe and Latin America with mutations in the factor 7 gene. Haemophilia : the official journal of the World Federation of Hemophilia. 2009. PMID: 18976247
- Mariani G, Bernardi F. Factor VII Deficiency. Seminars in thrombosis and hemostasis. 2009. PMID: 19598068
- Mariani G, Herrmann FH, Dolce A. Clinical phenotypes and factor VII genotype in congenital factor VII deficiency. Thrombosis and haemostasis. 2005. PMID: 15735798
- Mariani G, Herrmann FH, Bernardi F. Clinical manifestations, management, and molecular genetics in congenital factor VII deficiency: the International Registry on Congenital Factor VII Deficiency (IRF7). Blood. 2000. PMID: 10939805