GTPase KRas (mutated) (Mutated KRAS)

Mutated KRAS refers to oncogenic variants of the GTPase KRas protein, a membrane-bound regulatory GTPase that cycles between inactive GDP-bound and active GTP-bound states to control signal transduction. Common mutations at hotspots G12, G13, and Q61 (e.g., G12C, G12D, G13D, Q61H) impair GTP hydrolysis, leading to constitutive activation and downstream signaling via RAF-MEK-ERK, PI3K-AKT-mTOR, and other pathways that drive uncontrolled cell proliferation. These isoforms (primarily KRAS4B) differ in the hypervariable region (HVR) for membrane anchoring via farnesylation. Mutated KRAS is the most frequent oncogenic RAS form (85% of RAS mutations), prevalent in pancreatic (over 85%), colorectal, and lung cancers, making it a key therapeutic target with recent covalent inhibitors for specific mutants like G12C.

Other names

K-Ras (mutated)KRAS4B (mutated)KRAS4A (mutated)oncogenic KRASG12-mutated KRASG13-mutated KRASQ61-mutated KRAS

Covalent binding to G12C cysteine; Inhibition of GTP binding; Locking KRAS in inactive GDP-bound state; Allosteric inhibition of effector binding.