Journal of Blood Disorders & Transfusion

Abstract

Structural Modeling Analysis and Functional Characteristics of Two F10 Mutations (Asp413Asn and Gly420Arg)

Osayd Zohud, Siba Shanak, Husam Sallam, Zaidoun Salah and Hisham Darwish*

Factor X (FX), a vitamin K-dependent serine protease, plays a crucial role in coagulation, and mutations in the F10 gene can lead to FX deficiency. This study aimed to investigate the functional and structural consequences of two missense mutations, c.1237 G>A (Asp413Asn) and c.1258 G>A (Gly420Arg). Wild-type and mutant FX constructs were transfected into HEK293 cells to evaluate intracellular protein levels, secretion rates, and FX activity, as well as mRNA expression. The Asp413Asn mutant exhibited significantly lower intracellular protein levels, while Gly420Arg levels were similar to wild type. However, Asp413Asn showed higher secretion compared to both Gly420Arg and wild type. Both mutants displayed significantly reduced FX activity compared to wild type. Bioinformatics analysis revealed that Asp413 and Gly420 are highly conserved in the catalytic domain, and molecular modeling indicated that both mutations lead to damaging structural alterations. These findings suggest that the distinct functional impairments associated with Asp413Asn and Gly420Arg mutations contribute to the pathology of FX deficiency, highlighting the importance of these residues in maintaining FX activity.

Published Date: 2025-05-09; Received Date: 2025-04-09