Coagulation & Clotting Factors

Ashkenazi Jewish founder nonsense mutation in coagulation factor XI causing severe FXI deficiency (hemophilia C) in homozygotes and partial deficiency in heterozygotes; associated with surgical bleeding risk at mucosal sites and, paradoxically, reduced ischemic stroke and DVT risk

Ashkenazi Jewish founder missense mutation in coagulation factor XI causing impaired FXI dimerization; homozygotes develop hemophilia C (severe FXI deficiency) with post-surgical and trauma-related bleeding, while heterozygotes have partial deficiency with variable bleeding risk; the most prevalent FXI deficiency allele in Ashkenazi Jewish populations

Second most common inherited thrombophilia; the A allele raises prothrombin levels by 30%, increasing venous thromboembolism risk 2-5 fold and is highly actionable for women considering oral contraceptives

Factor V HR2 haplotype — a missense variant that mildly impairs the anticoagulant cofactor function of factor V; clinically significant mainly when co-inherited with Factor V Leiden, where the combination amplifies thrombotic risk 3- to 4-fold beyond Leiden alone

Upstream promoter variant in fibrinogen beta chain that elevates circulating fibrinogen levels and amplifies the acute-phase inflammatory response

Promoter variant in the fibrinogen beta-chain gene that upregulates FGB transcription, raising plasma fibrinogen levels and increasing cardiovascular and thrombotic risk

3' region variant in the fibrinogen gamma chain gene that shifts the gamma/gamma-prime isoform ratio, altering clot structure and increasing venous thromboembolism risk

Intronic variant in the Factor IX gene in near-perfect linkage disequilibrium with the rs6048 missense variant; the C allele tags the same modestly protective haplotype for deep vein thrombosis identified in the Bezemer 2009 GWAS

Missense variant in Factor XIII A subunit; the Leu34 allele accelerates thrombin-driven FXIII activation, producing finer and more fibrinolysis-susceptible fibrin clots — moderately protective against venous thromboembolism and myocardial infarction, with context-dependent effects at elevated fibrinogen

Common missense variant in the X-linked coagulation factor IX gene; the G allele is modestly protective against deep vein thrombosis, though its biological mechanism remains incompletely understood

Missense variant in the fibrinogen alpha chain (FGA) that substitutes alanine for threonine at position 312, altering the alphaC domain targeted by factor XIIIa cross-linking and producing lysis-resistant fibrin clots associated with elevated venous thromboembolism and pulmonary embolism risk

Rare missense variant in the fibrinogen gamma chain producing a substantially elevated risk of venous thromboembolism