Kirsten rat sarcoma virus oncogene homolog G12V (KRAS G12V) (KRAS G12V)

The Mutant KRAS G12V genomic locus refers to the specific chromosomal site of a missense mutation in the KRAS gene, where glycine is substituted by valine at codon 12. This genetic alteration results in the production of the KRAS G12V protein, a member of the small GTPase family that plays a pivotal role in intracellular signal transduction [1]. The G12V mutation impairs the protein's ability to hydrolyze GTP, locking it in a constitutively active state that drives oncogenic signaling through the MAPK and PI3K pathways [2]. This mutation is a hallmark of several aggressive cancers, particularly pancreatic ductal adenocarcinoma and colorectal cancer, where it promotes uncontrolled cell growth and survival [3]. Historically considered undruggable, the KRAS G12V protein is now the focus of intense therapeutic development, with non-covalent inhibitors like MRTX1133 designed to bind the switch II pocket and inhibit its activity [4]. Beyond protein inhibition, the genomic locus itself is a potential target for gene-editing technologies such as CRISPR/Cas9, which aim to permanently disrupt the oncogenic driver [5]. Understanding the interplay between the genomic mutation and the resulting protein function is essential for developing effective precision medicines for patients harboring this specific mutation.

Other names

KRAS G12VKirsten rat sarcoma 2 viral oncogene homolog G12Vp21 Ras G12Vc-K-ras G12V

Non-covalent inhibition of the KRAS G12V protein by binding to the switch II pocket, stabilizing the inactive state or preventing effector binding in the active state.