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F11
coagulation factor XI
The F11 gene provides instructions for making coagulation factor XI, a protein crucial for normal blood clot formation following injury. F11 encodes factor XI, a key component of the coagulation cascade that helps stop bleeding.
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 that plays a vital role in the body's haemostasis system. This system is a complex network of processes designed to stop bleeding and aid in wound healing. Factor XI contributes to the formation of stable blood clots, which are essential for sealing damaged blood vessels after an injury.
Disruptions to the F11 gene can lead to reduced or non-functional factor XI, impacting the body's ability to form clots effectively. This can result in an increased risk of bleeding, characteristic of conditions like Factor XI deficiency.
What the gene does
The F11 gene provides the blueprint for coagulation factor XI, a protein synthesised primarily by liver cells. Factor XI circulates in the bloodstream in an inactive state until it is activated as part of the coagulation cascade, a series of biochemical reactions that culminate in blood clot formation. Upon vascular injury, the cascade initiates, activating factor XI.
Once activated, factor XI interacts with other coagulation factors, contributing to the conversion of prothrombin into its active form, thrombin. Thrombin, in turn, is critical for transforming fibrinogen into fibrin. Fibrin strands then polymerise to form the mesh-like structure that stabilises a blood clot, effectively sealing the damaged blood vessel and halting blood loss.
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Chromosome location
The F11 gene is located on the long arm (q) of chromosome 4, specifically at position 4q35.2. This location indicates its precise address within the human genome. Understanding a gene's chromosomal location can be important for genetic mapping and identifying its proximity to other genes.
Protein structure
The coagulation factor XI protein, encoded by the F11 gene, consists of 625 amino acids. It features a distinct domain organisation essential for its function. The protein contains 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), which is characteristic of serine proteases and is crucial for the protein's enzymatic activity in the coagulation cascade.
Key variants
Genetic variations within the F11 gene can alter the production or function of coagulation factor XI. These variations, often called mutations, can range from single nucleotide changes to larger deletions or insertions within the gene sequence. Over 250 different variants in the F11 gene have been identified that are associated with inherited bleeding conditions.
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.1443del | p.Ile481fs | Pathogenic | ★★☆☆ | Plasma factor XI deficiency |
c.214C>T | p.Arg72Ter | Pathogenic | ★★☆☆ | Hereditary factor XI deficiency disease |
c.325+1G>A | - | Pathogenic | ★★☆☆ | Plasma factor XI deficiency |
c.569T>C | p.Leu190Pro | Pathogenic/Likely pathogenic | ★★☆☆ | Plasma factor XI deficiency |
c.688T>A | p.Cys230Ser | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary factor XI deficiency disease |
c.738G>A | p.Trp246Ter | Pathogenic | ★★☆☆ | Plasma factor XI deficiency |
c.981C>A | p.Cys327Ter | Pathogenic | ★★☆☆ | Plasma factor XI 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 F11 gene are primarily associated with Factor XI deficiency, also known as Rosenthal syndrome. This condition is an inherited bleeding disorder characterised by reduced levels or activity of coagulation factor XI. While often mild, individuals with Factor XI deficiency may experience symptoms such as easy bruising, nosebleeds, prolonged bleeding after surgery or trauma, and bleeding into the skin or gums.
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 recognised within the NHS Genomic Medicine Service due to its clinical significance. It is included on several NHS national genomic test directories. Specifically, F11 is part of the 'Bleeding and platelet disorders' (R90), 'Factor XI deficiency' (R120), and 'Inherited bleeding disorders' gene panels, all of which are classified as 'green' indicating strong evidence for gene-disease association and clinical utility.
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 the genetic instructions for creating coagulation factor XI, a protein made primarily in the liver. This protein is a critical component of the body's blood clotting system, helping to form stable clots to stop bleeding after an injury.
What is Factor XI deficiency?
Factor XI deficiency is an inherited bleeding disorder caused by variants in the F11 gene. It results in lower levels or reduced activity of coagulation factor XI, which can lead to symptoms like easy bruising, prolonged bleeding, and nosebleeds.
How is Factor XI deficiency inherited?
Factor XI deficiency is typically inherited in an autosomal recessive pattern. This means an individual must inherit two altered copies of the F11 gene (one from each parent) to develop the condition. Individuals with one altered copy are usually carriers and do not typically show symptoms.
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