GTPase KRas (Kirsten rat sarcoma viral oncogene homolog) (KRAS)

GTPase KRas, encoded by the KRAS gene (Kirsten rat sarcoma viral oncogene homolog), is a proto-oncogenic small GTPase functioning as a molecular switch in signal transduction pathways that regulate cell proliferation, differentiation, and survival[1][5][3]. KRas cycles between inactive (GDP-bound) and active (GTP-bound) states to transmit signals from membrane receptors to intracellular effectors, primarily through the RAS/MAPK pathway[5][6]. It is one of the most commonly mutated oncogenes in human cancers, with activating mutations—particularly at codons G12, G13, and Q61—causing constitutive signaling that drives malignant cell growth, resistance to certain therapies, and altered tumor microenvironment[1][9]. Drugs labeled as "KRAS inhibitors" typically refer to small-molecule inhibitors that selectively and covalently target the mutant G12C form of KRas, restoring normal regulation of cell growth[10]. Two isoforms, KRas4A and KRas4B, exist, differing in their C-terminal regions which affect membrane localization[2][4]. KRAS mutation status is an established biomarker in several cancers for both prognosis and therapy selection[9].

Other names

Kirsten rat sarcoma viral oncogene homologK-RasKRAS2c-Ki-rasKi-ras2p21 KRASKRas4AKRas4B

Covalent binding to the mutant cysteine 12 residue in KRAS G12C, locking the protein in its inactive GDP-bound state; Allosteric modulation of GTPase activity; Competitive inhibition of GTP/GDP binding