Rho guanine nucleotide exchange factor 12 (ARHGEF12)

Rho guanine nucleotide exchange factor 12 (ARHGEF12) is a cytoplasmic signaling protein encoded by the ARHGEF12 gene, functioning mainly as a guanine nucleotide exchange factor (GEF) for the RhoA small GTPase. It promotes the exchange of GDP for GTP on RhoA, switching it to an active state, which in turn activates downstream effectors controlling actin cytoskeleton organization and cellular processes like migration and proliferation. ARHGEF12 is a known effector of heterotrimeric G proteins (specifically GNA12 and GNA13) linked to G protein-coupled receptor signaling and may also act as a GTPase-activating protein (GAP) for GNA12 and GNA13. Clinically, ARHGEF12 can form gene fusions implicated in acute myeloid leukemia and is associated with other neoplastic and proliferative diseases.

Other names

Leukemia-associated RhoGEFLARGKIAA0382rho guanine nucleotide exchange factor 12RhoGEF12PRO2792ARHGC_HUMANKMT2A/ARHGEF12 fusion proteinGEF 12ARHGEF12

Drugs targeting this molecule would likely inhibit or modulate its GEF activity toward RhoA or its interaction with GPCR downstream signaling. Inhibition would impair activation of RhoA-mediated pathways important for cell movement and proliferation.