Coagulation factor VIII associated 3 (F8A3)

Coagulation factor VIII associated 3 (F8A3, also known as HAP40) is a protein encoded by the F8A3 gene. Despite the name, F8A3 is not a coagulation factor and does not have a direct role in blood clotting. The F8A3/HAP40 protein acts as an effector for the small GTPase RAB5A, promoting the recruitment of the huntingtin protein (HTT) onto early endosomes. This complex modulates endosome dynamics, decreasing their motility by promoting interactions with the actin cytoskeleton and inhibiting microtubule-based transport. The F8A3 gene is found in a region subject to copy number variation and is one of several genes (F8A1, F8A2, F8A3) with shared and possibly redundant functions. Its precise biological role is not well defined, but expression is abundant across tissue types. There is no direct evidence that F8A3 is a therapeutic target, nor are there approved drugs or known safety concerns related to this molecule[2]. Despite names suggesting a relationship to blood coagulation and Factor VIII, F8A3 is not the essential blood clotting protein Factor VIII (F8 gene). F8A3 is a distinct gene, coding for a protein primarily involved in endosomal trafficking, not in coagulation. Therefore, it is not considered a receptor, enzyme, or a classic drug target in therapeutic development[2]. The main therapeutic target in hemophilia A is Coagulation factor VIII (F8 gene), not F8A3[1]. F8A3 is often confused or conflated with Factor VIII due to nomenclature similarities. Mechanistic, disease, drug, and biomarker data are not established for F8A3[2].

Other names

40-kDa huntingtin-associated proteinF8A1HAP40CpG island proteinFactor VIII intron 22 proteincoagulation factor VIII-associated (intronic transcript) 3cpG island proteinfactor VIII intron 22 protein