Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine substitution mutant (KRAS G12C)

Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine substitution mutant, commonly abbreviated as KRAS G12C, is a specific point mutation in the KRAS gene where glycine at position 12 is replaced by cysteine. The resulting protein is a small GTPase involved in signal transduction pathways that regulate cell growth and survival. The G12C mutation causes the on/off switch function of KRAS to become stuck in an "on" position, leading to continuous and uncontrolled cellular proliferation—a hallmark feature driving tumorigenesis. This mutation is found most frequently in cancers such as non-small cell lung cancer (NSCLC) and metastatic colorectal cancer[1][2]. Targeted therapies like sotorasib have been developed specifically for tumors harboring this alteration. Detection relies on biomarker testing using either tissue or blood samples[1].

Other names

KRAS G12CKRAS p.G12CKirsten rat sarcoma viral oncogene homolog G12C mutantKRAS glycine 12 to cysteine mutation

Covalent inhibition of the mutant cysteine residue in the active site, locking KRAS in an inactive GDP-bound state[1]