RASAL2 Gene - Function, Mutations, and Disease Associations | NCBI, UniProt, ClinVar

RASAL2 (RAS protein activator like 2) encodes a member of the RAS GTPase-activating protein (GAP) family. The protein contains a PH domain, a C2 domain, and a GAP domain, and functions as a negative regulator of RAS signaling by stimulating the intrinsic GTPase activity of RAS proteins, converting them from the active GTP-bound state to the inactive GDP-bound state. RASAL2 has been implicated in both tumor suppression and oncogenesis depending on cellular context and isoform expression. It is also involved in cell adhesion, migration, and cytoskeletal organization.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• RAS signaling pathway (Reactome: R-HSA-6802957)

• MAPK signaling pathway (KEGG: hsa04010)

• Signaling by RAS mutants (Reactome: R-HSA-9649948)

• RAP1 signaling pathway (KEGG: hsa04015)

RASAL2 is a 1159-amino acid protein containing an N-terminal PH domain, a C2 domain, and a C-terminal GAP domain. It localizes to the cytoplasm and plasma membrane, where it negatively regulates RAS activity by accelerating GTP hydrolysis. Alternative splicing produces multiple isoforms with potentially distinct functions. RASAL2 is widely expressed, with highest levels in brain and colon. Its dysregulation contributes to cancer progression through both loss- and gain-of-function mechanisms.