Ras GTPase-activating protein nGAP (RASAL2)

Ras GTPase-activating protein nGAP (RASAL2) is an intracellular enzyme that belongs to the family of GTPase-activating proteins (GAPs), which negatively regulate the Ras signaling pathway by stimulating the hydrolysis of GTP to GDP on Ras, thereby inactivating Ras and downregulating Ras-mediated signal transduction. RASAL2 acts as a tumor and metastasis suppressor in various cancers, including breast cancer, by inhibiting uncontrolled cell growth and invasion. Loss or suppression of RASAL2—through genetic mutations, epigenetic silencing, or post-translational modifications—leads to hyperactivation of the Ras-ERK pathway and is associated with increased recurrence and metastasis, particularly in luminal B and triple-negative breast cancers. Furthermore, phosphorylated forms can be secreted in exosomes, potentially modulating tumor progression in recipient cells, and p-Rasal2 is emerging as a possible liquid-biopsy biomarker for aggressive disease. To date, RASAL2 is considered both a tumor suppressor and a context-dependent modulator of cancer progression without direct therapeutic targeting by approved drugs.

Other names

Ras protein activator-like 2NGAPnGAPRas GTPase activating protein-likeRASAL2/ACVR1 fusion