Coagulation Factor IX Padua (FIX-Padua) (FIX-Padua)

Coagulation Factor IX Padua is a hyperfunctional variant of the human Factor IX protein, resulting from a single nucleotide mutation that replaces arginine with leucine at position 338 (R338L) (Simioni et al., 2009, NEJM). This variant exhibits approximately 5- to 10-fold higher procoagulant activity compared to wild-type Factor IX, a property first identified in a young patient with severe idiopathic thrombosis. In modern therapeutics, FIX-Padua is primarily utilized as the transgene in adeno-associated virus (AAV) gene therapies for Hemophilia B, such as etranacogene dezaparvovec (Hemgenix) and fidanacogene elaparvovec (Beqvez) (FDA, 2022; FDA, 2024). By delivering the genetic sequence for this high-activity variant, these therapies can achieve sustained, therapeutic levels of clotting factor activity even with relatively low protein expression levels. As a serine protease, it functions within the intrinsic pathway of the coagulation cascade, where it is activated by Factor XIa or the Factor VIIa/Tissue Factor complex to subsequently activate Factor X, facilitating thrombin generation and clot formation (UniProt P00740).

Other names

Factor IX-R338LFIX-R338LCoagulation Factor IX (R338L)Factor IX Padua variantFIX-R338L variant

The Padua variant is a gain-of-function mutant of Factor IX used as a transgene in gene therapy to restore hemostasis in Hemophilia B patients. It possesses approximately 8-fold higher catalytic activity than wild-type Factor IX, enabling the achievement of therapeutic clotting levels at significantly lower vector doses (Monahan et al., 2021, Blood; Simioni et al., 2009, NEJM).