Kirsten rat sarcoma viral oncogene homolog GTPase, G12D mutant (KRAS G12D)

KRAS G12D refers to a specific *point mutation* in the KRAS gene, which substitutes glycine for aspartate at codon 12 (G12D) in the small GTPase protein. KRAS is a key regulator of cell signaling pathways controlling proliferation and survival. The G12D mutation impairs GTP hydrolysis, locking KRAS in a constitutively active, GTP-bound state that drives oncogenic signaling through pathways such as MAPK and PI3K, leading to uncontrolled cell growth and tumorigenesis[1][5][9]. KRAS G12D mutations are highly prevalent in pancreatic, colorectal, and lung cancers, and confer aggressive disease, metabolic reprogramming, and immune evasion[4][6]. Therapeutically, KRAS G12D is a validated but historically "undruggable" target; recent advances include both small molecule inhibitors (e.g., MRTX1133) and engineered protein inhibitors (e.g., monobodies) that specifically engage the unique switch II pocket of the mutant protein[9].

Other names

KRAS G12D mutantKRAS Gly12AspKRAS codon 12 aspartateKRAS-G12DKRAS (G12D)G12D KRAS

- Small molecule inhibition of GTPase activity - Allosteric inhibition at switch II pocket - Disruption of effector binding and downstream signaling - Engineered protein inhibition (e.g., monobodies blocking active conformation)[9]