RASA3 Gene - Function, Mutations, and Disease Associations

RASA3 (RAS p21 protein activator 3) encodes a member of the RAS GTPase-activating protein (GAP) family. The protein contains a pleckstrin homology (PH) domain, a C2 domain, and a catalytic GAP domain. It functions as a negative regulator of RAS signaling by stimulating the intrinsic GTPase activity of RAS proteins, converting them from the active GTP-bound form to the inactive GDP-bound form. RASA3 is involved in cell proliferation, differentiation, and migration. It is highly expressed in hematopoietic tissues and plays a critical role in erythropoiesis and platelet function.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• RAS signaling pathway (Reactome: R-HSA-5673001)

• Signaling by RAS mutants (Reactome: R-HSA-6802949)

• GTPase cycle (Reactome: R-HSA-9013408)

• RAF/MAP kinase cascade (Reactome: R-HSA-5673000)

RASA3 is a 1049-amino acid protein (UniProt Q14644) with a molecular weight of ~119 kDa. It contains an N-terminal pleckstrin homology (PH) domain (residues 48-155), a C2 domain (residues 175-280), and a C-terminal RAS-GAP domain (residues 720-920). The PH domain binds phosphoinositides, targeting the protein to the plasma membrane. The C2 domain mediates calcium-dependent phospholipid binding. The GAP domain accelerates GTP hydrolysis on RAS proteins, thereby terminating RAS signaling. RASA3 is highly expressed in hematopoietic tissues and is essential for proper erythropoiesis and platelet formation. Alternative splicing produces multiple isoforms.