factor ix padua

Factor IX Padua is a hyperactive variant of human coagulation factor IX carrying an arginine-to-leucine substitution at position 338 (R338L) that increases its specific clotting activity approximately 5- to 15-fold compared with wild-type factor IX, with about an 8-fold gain most consistently reported.[1][2] This gain-of-function variant forms the intrinsic Xase complex with activated factor VIII (FVIIIa) more efficiently, leading to faster activation of factor X and markedly enhanced thrombin generation while retaining normal activation and inactivation kinetics relative to wild-type factor IX.[1][2] Because of its substantially higher specific activity without a corresponding increase in thrombogenicity at equivalent activity levels, the Padua variant has become a preferred transgene payload in adeno-associated virus (AAV)–mediated liver-directed gene therapies for hemophilia B, enabling therapeutic factor IX activity at lower vector doses and reducing the risk of vector-related hepatotoxicity.[1][2] The variant was originally identified in a thrombophilic family from Padua, Italy, and has since been incorporated into multiple investigational and approved gene therapy products for congenital factor IX deficiency.[2][3][4]

Other names

factor ix r338lfix-r338l paduafix-r-338l paduafix-r 338l paduahyperactive factor ix padua variantpadua variant of factor ixf9 r338lf-9 r338lf 9 r338l