NRAs

NRAS, short for neuroblastoma RAS viral oncogene homolog, is a human gene encoding NRAS, a small GTPase of the Ras superfamily. The NRAS protein functions as a molecular switch that cycles between an inactive GDP-bound and an active GTP-bound state to regulate signal transduction from cell-surface receptors to intracellular pathways. It shares structural and functional features with other RAS proteins, such as HRAS and KRAS.

NRAS participates primarily in the MAPK/ERK signaling pathway, through activation of RAF kinases, MEK, and ERK, promoting cell proliferation and survival. It can also influence the PI3K/AKT pathway under certain contexts. Membrane localization, driven by post-translational lipid modifications, is essential for its signaling activity.

Mutations in NRAS are found in a subset of human cancers. The most common activating alterations occur at codons 12, 13, or 61, leading to constitutive, GTP-bound signaling independent of upstream receptors. NRAS mutations are particularly enriched in melanoma, and are also observed in subsets of hematologic malignancies and colorectal cancers.

Clinically, NRAS mutation status has diagnostic and prognostic significance in some cancers and can influence treatment decisions. Direct NRAS inhibitors are not widely available, so therapeutic strategies focus on targeting downstream effectors such as MEK inhibitors or combination regimens, with ongoing research to improve efficacy and overcome resistance in NRAS-mutant tumors.