GTPase KRas (G13A mutant) (KRAS G13A)

The KRAS G13A mutant allele refers to a specific oncogenic variant of the Kirsten rat sarcoma virus oncogene homolog (KRAS) gene, characterized by a point mutation at codon 13 that replaces glycine with alanine [1]. As a member of the small GTPase family, KRAS normally cycles between an active GTP-bound state and an inactive GDP-bound state to regulate signal transduction pathways such as MAPK/ERK and PI3K/AKT, which govern cell growth, differentiation, and survival [1][2]. The G13A mutation disrupts the protein's ability to hydrolyze GTP, leading to a constitutively active state that promotes oncogenesis and tumor progression [3]. This specific mutation is frequently identified in colorectal, lung, and pancreatic cancers, where it serves as both a diagnostic biomarker and a therapeutic target [4]. While early KRAS inhibitors were specific to the G12C mutation, current drug development efforts for G13A focus on SOS1 inhibitors that block nucleotide exchange and "RAS-multi" inhibitors that target the active "ON" state of various KRAS mutants [5][6].

Other names

Kirsten rat sarcoma virus oncogene homolog G13AKRAS p.G13Ap.Gly13AlaKRAS G13A

Inhibition of SOS1-mediated nucleotide exchange to prevent KRAS activation or direct binding to the active (GTP-bound) state of the KRAS protein to disrupt downstream signaling [5][6].