Factor X(St Louis II) - Identification of a glycine substitution at residue 7 and characterization of the recombinant protein

A molecular defect in factor X (fX) results from a point mutation that causes glycine substitution for gamma-carboxylated glutamic acid at position 7. The variant (fX(St. Louis II)) and wild type (fX(WT)) proteins were produced in a mammalian expression system and characterized. fX(St. Louis II) has <1% and similar to 3% of normal clotting activity in modified prothrombin time and partial thromboplastin time assays, respectively. The rate of activation of fX(St. Louis II) by factor VIIa and tissue factor is undetectable under conditions that result in complete activation of fX(WT); activation by factors VIIIa and IXa is similar to 30% of normal activation. The X-activating protein from Russell's viper venom activates fX(St. Louis II) completely but at a reduced rate. Thrombin generation on phoshopolipid vesicles or activated platelets is similar to 30% or similar to 5%, respectively. Membrane-dependent autolysis is markedly reduced for fX(St. Louis II). In reactions that are not surface-dependent, fX(St. Louis II) is nearly identical to that of fX(WT). The rate of inhibition by antithrombin is indistiguishable, as is the rate of thrombin formation in the absence of phospholipid, with or without factor Va.