Clinically observed <i>RASA1</i> missense mutants exhibit diverse RasGAP protein behaviors.

ABSTRACT: The RASA1 gene is mutated in cerebrovascular disorders and cancer, yet how the resulting mutations in the GTPase Activating Protein, RasGAP (p120RasGAP, RASA1) dysregulate signaling remains poorly understood. Here, we catalogue currently reported disease-associated mutations in RASA1 and assess their impact on RasGAP protein in vitro. On mapping these mutations onto experimental structures and structural models of RasGAP we identify regions that suggest functional impact. We assess key mutations within these regions for their effects on protein expression, thermal stability, and their interactions with a known binding partner, p190RasGAP. We then assess Michaelis-Menten kinetics of the mutant RasGAP proteins towards Ras. Together, we find that disease-associated RasGAP

SUBMITTER: Paul ME 

PROVIDER: S-EPMC12621883 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature