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F7
coagulation factor VII
The F7 gene provides instructions for making coagulation factor VII, a protein essential for the blood clotting process, and is linked to Factor VII deficiency. The F7 gene encodes coagulation factor VII, a vital protein within the complex cascade that leads to blood clot formation.
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 producing coagulation factor VII, a crucial component of the body's coagulation system. Factor VII is a key player in haemostasis, the body's mechanism for preventing blood loss. Through a carefully orchestrated series of molecular interactions, this protein helps generate stable clots at sites of vascular injury, which are necessary to prevent ongoing bleeding and begin tissue repair.
Coagulation factor VII is primarily synthesised by liver cells and circulates in the bloodstream in an inactive form. It becomes activated following blood vessel damage, initiating a cascade of events that promotes clot formation.
What the gene does
Coagulation factor VII plays an essential role in the clotting cascade, a sequence of activation events involving multiple proteins. Once triggered by vascular damage, activated factor VII helps initiate downstream reactions by turning on other coagulation factors in a step-wise fashion. This sequential activation process ultimately promotes the conversion of fibrinogen, a soluble plasma protein, into fibrin, which assembles into the mesh-like framework that stabilises a blood clot.
This precise, step-wise process ensures that clotting only occurs when and where it is needed, preventing excessive bleeding while avoiding inappropriate clot formation. Pathogenic variants in F7 can disrupt this delicate balance, leading to a reduced ability to form clots.
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Chromosome location
The F7 gene is located on chromosome 13 at band 13q34. This chromosomal location indicates its specific position on the long arm ('q') of chromosome 13.
Protein structure
The coagulation factor VII protein is composed of 466 amino acids and features several distinct functional domains. The protein contains a Gla domain spanning amino acids 61-105, two EGF-like domains (EGF-like 1, which binds calcium, from amino acids 106-142, and EGF-like 2 from amino acids 147-188), and a Peptidase S1 domain located from amino acids 213-452.
Key variants
Variants within the F7 gene can affect the production, structure, or function of coagulation factor VII. Many genetic changes (almost 300) in F7 have been identified that are associated with a rare bleeding disorder. These variants can lead to a decrease in the amount of functional factor VII protein, impairing the blood's ability to clot effectively.
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.64G>A | p.Val22Ile | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital factor VII deficiency |
c.739+1G>A | - | 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 Factor VII deficiency, an autosomal recessive inherited bleeding disorder. Individuals with this condition experience a range of bleeding symptoms, varying in severity. Common manifestations include nosebleeds, easy bruising, gum bleeding, and prolonged or excessive bleeding after surgery or physical injury. In severe cases, serious bleeding complications may occur.
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 NHS England Genomic Medicine Service national test panels. It is part of the 'Bleeding and platelet disorders' (R90) and 'Factor VII deficiency' (R116) panels. F7 is also listed under the broader 'Inherited bleeding disorders' panel, indicating its significance in the diagnosis and management of these conditions within the UK.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the role of coagulation factor VII?
Coagulation factor VII is a protein produced by the F7 gene that is essential for blood clotting. It initiates a crucial part of the clotting cascade, helping to form fibrin, which is the main component of a blood clot.
What is Factor VII deficiency?
Factor VII deficiency is an inherited bleeding disorder caused by variants in the F7 gene. It leads to a reduced amount or function of coagulation factor VII, resulting in symptoms like easy bruising, nosebleeds, and prolonged bleeding.
How is Factor VII deficiency inherited?
Factor VII deficiency typically follows an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of the altered F7 gene (one from each parent) to develop the condition.
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