Coagulation & Clotting Factors

Frameshift deletion in coagulation factor XI causing complete loss of the FXI protein; homozygous carriers develop hemophilia C (severe FXI deficiency) with bleeding after surgery and trauma, while heterozygous carriers may have partial deficiency with variable bleeding risk

Frameshift deletion in coagulation factor XI causing likely-pathogenic partial or severe FXI deficiency (hemophilia C); heterozygous carriers have partial deficiency with variable surgical bleeding risk, homozygotes face severe deficiency with ~60% bleeding rate at high-risk surgical sites

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

Intronic regulatory variant in SERPINE2 that modulates expression of Protease Nexin-1, the most potent tissue thrombin inhibitor, shifting fibrinolytic balance and elevating venous thromboembolism risk

Promoter insertion/deletion polymorphism that controls PAI-1 (plasminogen activator inhibitor-1) expression; the 4G allele (G on the plus strand) raises PAI-1 levels, suppresses fibrinolysis, and increases risk of venous thromboembolism, myocardial infarction, preeclampsia, and recurrent pregnancy loss

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

Upstream promoter variant in fibrinogen beta chain that increases IL-6-driven FGB transcription, raising plasma fibrinogen levels and amplifying cardiovascular and thrombotic risk

Upstream promoter variant in fibrinogen beta chain that is associated with lower circulating fibrinogen and a modestly reduced risk of coronary artery disease and atherosclerosis

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

5' UTR variant that reduces Factor XII translation efficiency, lowering plasma FXII levels and reducing contact activation coagulation

Nonsense mutation in coagulation factor XI creating a premature stop codon, causing severe factor XI deficiency with surgical bleeding risk especially at high-fibrinolysis sites

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 by 22-37% per allele in multiple large GWAS

Regulatory tag variant in the Factor XII locus associated with plasma FXII activity levels and aPTT; the T allele tags lower Factor XII expression, which is paradoxically protective against arterial and venous thrombosis

Missense variant in the fibrinogen beta chain that elevates circulating fibrinogen levels and alters fibrin network architecture, with sex-specific effects on hypertension risk in men

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

Intronic KLKB1 variant whose T allele elevates plasma kallikrein enzymatic activity and associates with higher circulating endothelin and adrenomedullin surrogate markers — vasoactive peptides predictive of cardiac stress and heart failure

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 denser, lysis-resistant fibrin clots associated with elevated venous thromboembolism and pulmonary embolism risk

Rare missense variant in the fibrinogen gamma chain that disrupts fibrin polymerization, producing structurally abnormal clots and a substantially elevated risk of venous thromboembolism