G protein subunit alpha o1 (GNAO1)

G protein subunit alpha o1 (GNAO1) is a GTPase that forms the alpha subunit of the Go class of heterotrimeric G proteins, which are key signal transducers downstream of G protein-coupled receptors (GPCRs). As part of the GPCR signaling cascade, GNAO1 alternates between GTP- and GDP-bound forms, modulating the inhibition of adenylyl cyclase, decreasing intracellular cAMP levels, and regulating signaling to a wide range of effectors involved in neural circuitry, cytoskeletal organization, and neuronal growth cone dynamics. GNAO1 is highly expressed in the central nervous system, important for neuronal development, axon guidance, and proper neural network formation. Pathogenic GNAO1 variants cause severe developmental and epileptic encephalopathies (DEE17), involuntary movement disorders, and profound neurodevelopmental delay, with symptoms often appearing early in infancy. While several neurological disorders are associated with GNAO1 dysfunction, there are currently no approved drugs that specifically target this protein; treatment remains supportive or symptomatic.

Other names

Guanine nucleotide-binding protein G(o) subunit alphaG-ALPHA-oDEE17EIEE17GNAOHG1GNEDIMguanine nucleotide binding protein (G protein), alpha activating activity polypeptide Oheterotrimeric guanine nucleotide-binding protein 1Gguanine nucleotide-binding regulatory protein 2

No specific drugs targeting GNAO1 are approved; general mechanism—modulation of downstream signaling in GPCR pathways, most notably inhibition of adenylyl cyclase and modulation of Rho and MAPK pathways.