Kirsten rat sarcoma viral oncogene homolog (KRAS) – Glycine 12 Aspartate mutant (KRAS(G12D))

KRAS G12D mutant protein is a variant of the KRAS protein, a small GTPase that plays a central role in cell signaling pathways regulating proliferation, differentiation, and survival. The G12D mutation impairs intrinsic GTPase activity, leading to constitutive activation of KRAS signaling. This promotes uncontrolled cellular proliferation, drives transformation of normal epithelial cells into malignant ones, enhances invasion and metastasis capabilities, and increases resistance to apoptosis. G12D is especially common in pancreatic cancer but also found across NSCLC. Direct targeting has been historically difficult, but recent advances include engineered proteins or peptides that exploit unique features introduced by the mutation, and small-molecule inhibitors targeting S-II pocket are under clinical investigation.

Other names

KRAS G12DK-Ras G12DKRAS(G12D) mutant protein

Inhibition of KRAS(G12D) activity