Gene: F2

Alternate names for this Gene: PT|RPRGL2|THPH1

Gene Summary: This gene encodes the prothrombin protein (also known as coagulation factor II). This protein is proteolytically cleaved in multiple steps to form the activated serine protease thrombin. The activated thrombin enzyme plays an important role in thrombosis and hemostasis by converting fibrinogen to fibrin during blood clot formation, by stimulating platelet aggregation, and by activating additional coagulation factors. Thrombin also plays a role in cell proliferation, tissue repair, and angiogenesis as well as maintaining vascular integrity during development and postnatal life. Peptides derived from the C-terminus of this protein have antimicrobial activity against E. coli and P. aeruginosa. Mutations in this gene lead to various forms of thrombosis and dysprothrombinemia. Rapid increases in cytokine levels following coronavirus infections can dysregulate the coagulation cascade and produce thrombosis, compromised blood supply, and organ failure.

Gene is located in Chromosome: 11

Location in Chromosome : 11p11.2

Description of this Gene: coagulation factor II, thrombin

Type of Gene: protein-coding

rs5899 in F2 gene and Blood Protein Measurement PMID 30072576 2018 Co-regulatory networks of human serum proteins link genetics to disease.

rs1799963 in F2 gene and Cerebrovascular accident PMID 26908601 2016 Genome-wide association analysis of self-reported events in 6135 individuals and 252 827 controls identifies 8 loci associated with thrombosis.

PMID 27031503 2016 Prevalence and Geographical Variation of Prothrombin G20210A Mutation in Patients with Cerebral Vein Thrombosis: A Systematic Review and Meta-Analysis.

PMID 15059842 2004 The prothrombin 3'end formation signal reveals a unique architecture that is sensitive to thrombophilic gain-of-function mutations.

PMID 11443298 2001 Increased efficiency of mRNA 3' end formation: a new genetic mechanism contributing to hereditary thrombophilia.

PMID 19652888 2009 The genetics of venous thromboembolism. A meta-analysis involving approximately 120,000 cases and 180,000 controls.

rs61884307 in F2 gene and Child Development Disorders, Pervasive PMID 28540026 2017 Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

rs1799963 in F2 gene and Deep Vein Thrombosis PMID 26908601 2016 Genome-wide association analysis of self-reported events in 6135 individuals and 252 827 controls identifies 8 loci associated with thrombosis.

rs2070850 in F2 gene and High density lipoprotein measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 20686565 2010 Biological, clinical and population relevance of 95 loci for blood lipids.

PMID 30926973 2019 Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids.

PMID 24097068 2013 Discovery and refinement of loci associated with lipid levels.

PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

rs121918477 in F2 gene and Inherited Factor II deficiency PMID 6405779 1983 Determination of the amino acid substitution in human prothrombin type 3 (157 Glu leads to Lys) and the localization of a third thrombin cleavage site.

PMID 3801671 1987 Prothrombin Tokushima: characterization of dysfunctional thrombin derived from a variant of human prothrombin.

PMID 3771562 1986 Molecular defect of prothrombin Barcelona. Substitution of cysteine for arginine at residue 273.

PMID 2719946 1989 Substitution of valine for glycine-558 in the congenital dysthrombin thrombin Quick II alters primary substrate specificity.

PMID 1354985 1992 Prothrombin Salakta: substitution of glutamic acid-466 by alanine reduces the fibrinogen clotting activity and the esterase activity.

PMID 1349838 1992 Detection of a single base substitution of the gene for prothrombin Tokushima. The application of PCR-SSCP for the genetic and molecular analysis of dysprothrombinemia.

PMID 14962227 2004 Prothrombin Shanghai: hypoprothrombinaemia caused by substitution of Gla29 by Gly.

PMID 7792730 1995 Prothrombin Frankfurt: a dysfunctional prothrombin characterized by substitution of Glu-466 by Ala.

PMID 3242619 1988 Identification of the primary structural defect in the dysthrombin thrombin Quick I: substitution of cysteine for arginine-382.

PMID 1421398 1992 Prothrombin Himi: a compound heterozygote for two dysfunctional prothrombin molecules (Met-337-->Thr and Arg-388-->His).

PMID 7865694 1994 Prothrombin Padua I: incomplete activation due to an amino acid substitution at a factor Xa cleavage site.

PMID 3567158 1987 Prothrombin Tokushima, a replacement of arginine-418 by tryptophan that impairs the fibrinogen clotting activity of derived thrombin Tokushima.

PMID 9569177 1998 Geographic distribution of the 20210 G to A prothrombin variant.

PMID 19289024 2009 Thrombophilia: 2009 update.

rs1799963 in F2 gene and Ischemic stroke PMID 26908601 2016 Genome-wide association analysis of self-reported events in 6135 individuals and 252 827 controls identifies 8 loci associated with thrombosis.

rs1799963 in F2 gene and Pulmonary Embolism PMID 26908601 2016 Genome-wide association analysis of self-reported events in 6135 individuals and 252 827 controls identifies 8 loci associated with thrombosis.

rs776618390 in F2 gene and Reduced prothrombin activity PMID 31064749 2019 Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders.

rs61884307 in F2 gene and Schizophrenia PMID 28540026 2017 Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

rs2070850 in F2 gene and Serum HDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 20686565 2010 Biological, clinical and population relevance of 95 loci for blood lipids.

PMID 24097068 2013 Discovery and refinement of loci associated with lipid levels.

rs1799963 in F2 gene and THROMBOPHILIA DUE TO THROMBIN DEFECT PMID 8696333 1996 A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.

PMID 11358905 2001 Variable phenotypic presentation of iron overload in H63D homozygotes: are genetic modifiers the cause?

PMID 19159930 2009 Genetic screening for HFE hemochromatosis in 6,020 Danish men: penetrance of C282Y, H63D, and S65C variants.

PMID 2429850 1986 Can maximum ouabain-sensitive 86Rb+ uptake rate be obtained by increasing Na+ influx?

PMID 9106528 1997 Mutation analysis of the HLA-H gene in Italian hemochromatosis patients.

PMID 8896550 1996 Haemochromatosis and HLA-H.

PMID 21243428 2011 Effect of HFE variants on sphingolipid expression by SH-SY5Y human neuroblastoma cells.

PMID 19560233 2011 HFE polymorphisms affect cellular glutamate regulation.

PMID 9462220 1997 A simple genetic test identifies 90% of UK patients with haemochromatosis. The UK Haemochromatosis Consortium.

PMID 11874997 2002 A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation.

PMID 23429074 2013 A mutation in the HFE gene is associated with altered brain iron profiles and increased oxidative stress in mice.

PMID 19554541 2009 HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity.

PMID 21349849 2011 Mutant HFE H63D protein is associated with prolonged endoplasmic reticulum stress and increased neuronal vulnerability.

PMID 11904676 2002 Co-selection of the H63D mutation and the HLA-A29 allele: a new paradigm of linkage disequilibrium?

rs5896 in F2 gene and Tonometry PMID 29617998 2018 Genome-wide association analyses identify new loci influencing intraocular pressure.

rs1799963 in F2 gene and Venous Thromboembolism PMID 25772935 2015 Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism.

PMID 31676865 2019 Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease.

PMID 26908601 2016 Genome-wide association analysis of self-reported events in 6135 individuals and 252 827 controls identifies 8 loci associated with thrombosis.

PMID 31420334 2019 Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.

PMID 28373160 2017 Genetic Analysis of Venous Thromboembolism in UK Biobank Identifies the ZFPM2 Locus and Implicates Obesity as a Causal Risk Factor.