Kirsten rat sarcoma viral oncogene homolog G12V mutant (KRAS G12V)

Kirsten rat sarcoma viral oncogene homolog (KRAS) is a small guanosine triphosphatase (GTPase) that plays a central role in regulating cell growth and signal transduction. The KRAS G12V mutation refers to a specific missense alteration where glycine at position 12 is replaced by valine. This change impairs the ability of regulatory proteins called GAPs (GTPase activating proteins) to bind and stimulate hydrolysis of bound GTP, resulting in constitutive activation of downstream signaling pathways that drive uncontrolled cell proliferation[3]. The KRAS gene is one of the most frequently mutated genes in human cancers, with codon 12 mutations being especially common. The G12V variant has been shown to promote tumorigenesis and confer resistance to some targeted therapies. Therapeutic targeting has historically been challenging due to structural features that make drug binding difficult; however, recent research has identified peptides such as H‑REV107 that can directly interact with and inhibit this mutant form by stabilizing its inactive state[1]. The presence of this mutation serves both as an important biomarker for cancer diagnosis/prognosis and as an emerging therapeutic target under active investigation[4][2].

Other names

KRAS G12VKRAS glycine 12 to valine mutationOncogenic KRAS G12V mutantMutant KRAS (G12V)

Inhibitors may block the activation function by stabilizing the inactive GDP-bound state or preventing effector interactions[1].