KRAS Gene: Function, Mutations, and Associated Diseases

KRAS (Kirsten rat sarcoma viral oncogene homolog) is a proto-oncogene that encodes a small GTPase protein involved in signal transduction. It acts as a molecular switch, cycling between an active GTP-bound state and an inactive GDP-bound state. KRAS regulates cell proliferation, differentiation, and survival by transmitting signals from cell surface receptors (e.g., EGFR) to downstream pathways such as MAPK/ERK and PI3K/AKT. Somatic mutations in KRAS, particularly at codons 12, 13, and 61, result in constitutive activation, leading to uncontrolled cell growth and tumorigenesis. KRAS is one of the most frequently mutated oncogenes in human cancers, including pancreatic, colorectal, and lung adenocarcinomas.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• MAPK/ERK signaling pathway

• PI3K/AKT signaling pathway

• RAS signaling pathway

• EGFR signaling pathway

• RalGDS signaling pathway

The KRAS protein is a 21 kDa small GTPase that localizes to the plasma membrane via a C-terminal CAAX motif. It cycles between active GTP-bound and inactive GDP-bound states, regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). In its active state, KRAS binds to effector proteins such as RAF, PI3K, and RalGDS, initiating signaling cascades that control cell proliferation, survival, and differentiation. Mutations at codons 12, 13, and 61 disrupt the intrinsic GTPase activity, locking KRAS in the active state and driving oncogenesis. KRAS is a major therapeutic target, with recent advances in G12C-specific inhibitors (e.g., sotorasib, adagrasib) showing clinical efficacy.