GTPase KRAS (G13D mutant) (KRAS G13D)

GTPase KRAS (G13D mutant) is a specific oncogenic variant of the Kirsten rat sarcoma viral oncogene homolog (KRAS) protein, where the glycine residue at position 13 is replaced by aspartic acid (UniProt P01116). This mutation disrupts the protein's ability to hydrolyze GTP, resulting in a constitutively active state that continuously stimulates downstream signaling pathways such as MAPK/ERK and PI3K/AKT/mTOR (PubMed: 29133767). These pathways are critical for cell growth, differentiation, and survival, and their dysregulation leads to uncontrolled tumor proliferation. KRAS G13D is a major driver in several malignancies, most notably colorectal cancer, where it is associated with distinct clinical behaviors compared to G12 mutations (PubMed: 33009388). Therapeutic approaches targeting this mutant include small-molecule inhibitors like RMC-6236 that bind the active state of the protein (PubMed: 35115308), as well as immunotherapies like the ELI-002 peptide vaccine and mRNA-5671 that target the G13D neoantigen peptide presented on the cell surface (ClinicalTrials.gov: NCT04594213, NCT04853017).

Other names

KRAS G13DKirsten rat sarcoma virus oncogene homolog G13Dp.G13Dp21 Ras G13DKRAS G13D neoantigen peptide

Direct inhibition of the KRAS protein to prevent downstream signaling (PubMed: 35115308) or induction of an adaptive immune response against the G13D neoantigen peptide (ClinicalTrials.gov: NCT04594213).