G12S

G12S denotes a substitution at position 12 in the KRAS protein, where glycine is replaced by serine. KRAS is a small GTPase that regulates cell growth and differentiation, and codon 12 mutations are among the most common activating alterations in human cancers.

Mechanism: The substitution disrupts the protein's intrinsic GTPase activity, locking KRAS in an active, GTP-bound conformation that continuously stimulates downstream signaling through pathways such as MAPK/ERK and PI3K/AKT. This promotes uncontrolled cell proliferation and survival.

Clinical significance: KRAS G12S is an oncogenic driver observed in several cancer types, though it is less frequent than other G12 substitutions (for example G12D or G12V). The mutation contributes to tumorigenesis and can influence tumor behavior and response to therapy.

Diagnosis and testing: G12S is typically identified through DNA sequencing of tumor tissue or circulating tumor DNA using targeted panels or comprehensive genomic profiling. Accurate detection supports diagnostic workups and informs treatment planning where applicable.

Therapeutic considerations: There are no approved therapies targeting G12S specifically. Treatment generally follows standard oncologic approaches, while research explores strategies such as inhibiting downstream signaling, targeting upstream regulators, or developing broader KRAS inhibitors.

See also: KRAS, G12C, G12D, G12V.