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F11
coagulation factor XI
The F11 gene provides instructions for making coagulation factor XI, a protein essential for the blood clotting process, playing a vital role in preventing excessive bleeding. The F11 gene encodes coagulation factor XI, a key component of the coagulation cascade.
F11 is located on the long (q) arm of chromosome 4, at band 4q35.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The F11 gene is responsible for producing coagulation factor XI, a protein involved in the complex cascade of events that leads to blood clot formation. This process is crucial for stopping bleeding following an injury.
Factor XI circulates in the bloodstream in an inactive form, primarily synthesised by liver cells. It becomes activated in response to vessel damage, contributing to the chain reactions that convert prothrombin into thrombin, and subsequently fibrinogen into fibrin, which forms the structure of a blood clot.
What the gene does
Coagulation factor XI, encoded by the F11 gene, is a serine protease that participates in the intrinsic pathway of blood coagulation. Following an injury, activated factor XI plays a critical role in amplifying the clotting response. It activates factor IX, which in turn activates factor X, leading to the generation of thrombin. Thrombin is essential for converting fibrinogen into fibrin, the main structural component of a blood clot.
The protein's function is vital for maintaining haemostasis, the body's ability to prevent and stop bleeding. Disruptions in F11 function can impair the coagulation cascade, leading to an increased tendency to bleed.
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Chromosome location
The F11 gene is located on chromosome 4 at position 4q35.2. This specific genomic address helps to identify where the gene resides within the human genome and is important for genetic mapping and research.
Protein structure
The coagulation factor XI protein consists of 625 amino acids. It features a modular structure, including four Apple domains: Apple 1 (amino acids 20-103), Apple 2 (amino acids 110-193), Apple 3 (amino acids 200-283), and Apple 4 (amino acids 291-374). These are followed by a Peptidase S1 domain (amino acids 388-623). The Apple domains are thought to be involved in protein-protein interactions, while the Peptidase S1 domain contains the catalytic site responsible for its enzymatic activity in the coagulation cascade.
Key variants
Variants within the F11 gene can alter the structure or function of coagulation factor XI, leading to reduced or absent protein activity. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions, and their impact on protein function can vary significantly. Understanding these variants is crucial for diagnosing inherited bleeding disorders.
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.1026G>T | p.Gly342= | Pathogenic/Likely pathogenic | ★★☆☆ | Plasma factor XI deficiency |
c.1060G>A | p.Gly354Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Plasma factor XI deficiency |
c.1103G>A | p.Gly368Glu | Pathogenic | ★★☆☆ | Hereditary factor XI deficiency disease |
c.1135+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Plasma factor XI deficiency |
c.1238_1239del | p.Arg413fs | Pathogenic | ★★☆☆ | Hereditary factor XI deficiency disease |
c.1270C>T | p.Gln424Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary factor XI deficiency disease |
c.1411C>T | p.Gln471Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Plasma factor XI deficiency |
c.1416T>G | p.Tyr472Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary factor XI deficiency disease |
c.1443del | p.Ile481fs | Pathogenic | ★★☆☆ | Plasma factor XI deficiency |
c.1448del | p.Leu483fs | Pathogenic | ★★☆☆ | Hereditary factor XI deficiency disease |
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 F11 gene are primarily associated with an inherited bleeding disorder known as Factor XI deficiency. This condition typically follows an autosomal recessive inheritance pattern. Individuals with Factor XI deficiency may experience symptoms such as nosebleeds, easy bruising, bleeding under the skin, gum bleeding, and prolonged or excessive bleeding following trauma, surgery, or dental procedures.
Inheritance pattern
Conditions caused by pathogenic F11 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 F11 gene is included in several UK NHS national genomic testing panels. It is covered under the 'Bleeding and platelet disorders' (R90), 'Factor XI deficiency' (R120), and 'Inherited bleeding disorders' panels, indicating its recognised clinical significance for genetic testing within the UK.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the F11 gene responsible for?
The F11 gene provides instructions for making coagulation factor XI, a protein that plays a key role in the blood clotting process. It helps form fibrin, which is essential for stopping bleeding after an injury.
How is Factor XI deficiency inherited?
Factor XI deficiency is typically inherited in an autosomal recessive pattern. This means an individual must inherit two copies of a pathogenic F11 gene variant, one from each parent, to develop the condition.
What are the common symptoms of Factor XI deficiency?
Common symptoms of Factor XI deficiency can include easy bruising, nosebleeds, gum bleeding, and prolonged or excessive bleeding after surgery, dental procedures, or trauma. The severity can vary among individuals.
References
- Puy C, Rigg RA, McCarty OJ. The hemostatic role of factor XI. Thrombosis research. 2016. PMID: 27207433
- Peretz H, Salomon O, Mor-Cohen R. Type I mutation in the F11 gene is a third ancestral mutation which causes factor XI deficiency in Ashkenazi Jews. Journal of thrombosis and haemostasis : JTH. 2013. PMID: 23332144
- Duga S, Salomon O. Congenital factor XI deficiency: an update. Seminars in thrombosis and hemostasis. 2013. PMID: 23929304
- He R, Chen D, He S. Factor XI: hemostasis, thrombosis, and antithrombosis. Thrombosis research. 2012. PMID: 22197449
- Emsley J, McEwan PA, Gailani D. Structure and function of factor XI. Blood. 2010. PMID: 20110423
- Duga S, Salomon O. Factor XI Deficiency. Seminars in thrombosis and hemostasis. 2009. PMID: 19598070
- Gomez K, Bolton-Maggs P. Factor XI deficiency. Haemophilia : the official journal of the World Federation of Hemophilia. 2008. PMID: 18312365