Kirsten rat sarcoma virus oncogene homolog G13D (KRAS G13D) (KRAS G13D)

GTPase KRas G13D is a specific oncogenic mutant of the Kirsten rat sarcoma virus oncogene (KRAS), a small GTPase that functions as a critical molecular switch in cellular signaling pathways such as MAPK/ERK and PI3K/AKT [1, 15]. The G13D mutation results from a substitution of glycine with aspartic acid at codon 13, which impairs the protein's intrinsic GTPase activity and its interaction with GTPase-activating proteins (GAPs) like NF1, leading to a constitutively active state [1, 2]. This persistent activation drives uncontrolled cell growth, survival, and metastasis, making it a key driver in colorectal, pancreatic, and lung cancers [1, 9]. Historically considered 'undruggable,' KRAS G13D is now a focal point for precision medicine, with novel therapies like the degrader ASP3082 and pan-RAS inhibitors under development [1, 8]. Interestingly, KRAS G13D-mutant colorectal cancers may exhibit unique sensitivity to EGFR inhibitors like cetuximab compared to other KRAS mutants, due to its distinct biochemical interaction with neurofibromin [2, 4, 11].

Other names

KRAS G13DKirsten rat sarcoma 2 viral oncogene homolog G13Dp21 Ras G13DKRAS p.G13D

Inhibition of the KRAS G13D mutant protein through direct binding, targeted degradation (PROTACs), or indirect blockade of upstream activators (SOS1) and downstream signaling effectors (RAF/MEK/ERK) [1, 8, 9, 15]