Cdc42 guanine nucleotide exchange factor 9 (ARHGEF9)

Cdc42 guanine nucleotide exchange factor 9 (ARHGEF9) is a brain-enriched guanine nucleotide exchange factor (GEF) that primarily functions as an activator of the small GTPase Cdc42 and related Rho-family GTPases. The encoded protein, collybistin, is a multi-domain scaffolding enzyme responsible for recruiting and clustering gephyrin and GABA_A receptors at inhibitory synapses, chiefly in neurons of the central nervous system. Through these interactions, collybistin orchestrates the structural and functional organization of inhibitory postsynaptic membranes, influencing the balance of excitation and inhibition in neuronal circuits. Mutations in ARHGEF9 disrupt inhibitory synapse architecture, leading to intellectual disability, epilepsy, and related neurodevelopmental and behavioral phenotypes, particularly in an X-linked inheritance pattern. No currently approved drugs directly target ARHGEF9.

Other names

Rho guanine nucleotide exchange factor 9ARHDH9KIAA0424PEM-2CollybistinPEM-2 homologRac/Cdc42 guanine nucleotide exchange factor 9Collybistin (commonly used protein name)DEE8EIEE8HPEM-2PEM2hPEM-2 collybistin

Not applicable (no direct drugs known). Dysregulation of ARHGEF9 impacts synaptic GABAergic and glycinergic signaling.