Gephyrin (GPHN)

Gephyrin is a multifunctional protein encoded by the GPHN gene that acts as the principal scaffolding protein at inhibitory postsynaptic sites in the central nervous system. It is essential for the clustering and anchoring of glycine receptors and gamma-aminobutyric acid type A (GABA_A) receptors at inhibitory synapses, enabling effective fast synaptic inhibition. Structurally, gephyrin contains three domains—G (N-terminal), C (linker domain), and E (C-terminal)—and multimerizes into hexagonal lattices beneath the postsynaptic membrane. It also performs enzymatic functions in non-neuronal tissue, catalyzing the final steps in the biosynthesis of the molybdenum cofactor, which is critical for several metabolic enzymes. Mutations in gephyrin cause rare, severe genetic disorders with early-onset neurodegeneration, highlighting its essential biological roles in both the brain and peripheral tissues.

Other names

Molybdopterin adenylyltransferaseMolybdopterin molybdenumtransferaseGPHKIAA1385MPT adenylyltransferaseMPT Mo-transferaseGEPHDomain GDomain EGPHRYNHKPX1MOCODC

Not applicable (therapeutic targeting is indirect; modulates receptor clustering and synapse phenotypes)