KRAS, HRAS, and NRAS mutant proteins (KRAS, HRAS, NRAS)

KRAS, HRAS, and NRAS are members of the RAS family of small GTPase enzymes, acting as molecular switches that regulate key signaling pathways, most notably the RAF-MEK-ERK signaling cascade involved in cell proliferation, differentiation, and survival[4][5]. Mutations in these genes, most commonly at codons 12, 13, and 61, result in a constitutively active (GTP-bound) state that drives tumorigenesis by promoting uncontrolled cell growth and survival[3][4][5]. These mutant proteins are among the most frequently altered oncogenes in human cancers and serve as major therapeutic targets in oncology[1][5]. Different isoforms and mutations show diverse biochemical and transforming properties, impacting the success and resistance patterns of targeted therapeutics[3][5]. Targeted inhibition (especially of mutant KRAS G12C) and modification of RAS-driven signaling are areas of intense research and drug development, though challenges remain in specificity, resistance, and toxicity[5]. RAS mutation status is a well-established biomarker for cancer diagnosis, prognosis, and treatment selection, particularly in lung, colorectal, and pancreatic cancers[5].

Other names

RAS oncogene familyRAS mutantsmutant RAS proteinsRAS isoforms

Covalent binding to mutant cysteine in KRAS G12C\nInhibition of nucleotide exchange or GTPase activity\nInhibition of post-translational modifications (e.g., farnesylation)\nInhibition of effector binding (e.g., inhibition of RAF-MEK-ERK signaling)