Glutamate [NMDA] receptor subunit epsilon-4 (GRIN2D)

Glutamate [NMDA] receptor subunit epsilon-4 (encoded by the GRIN2D gene, also known as GluN2D) is a modulatory subunit of the NMDA receptor, a type of ligand-gated ion channel in the central nervous system[1][2]. The NMDA receptor is a heterotetramer typically composed of two GluN1 subunits and two GluN2 subunits (GluN2A-D), with GluN2D imparting unique pharmacological and biophysical properties to the receptor, including high glutamate potency, relatively lower magnesium block, and slow deactivation kinetics[2]. NMDA receptors are critical for synaptic transmission, plasticity (including long-term potentiation), learning, memory, and neurodevelopment[2][3]. Variants in GRIN2D cause developmental and epileptic encephalopathy (DEE46) and other severe neurodevelopmental disorders, often presenting with intellectual disability, seizures, and movement disorders[2]. Drugs such as memantine and ketamine act as non-competitive antagonists at NMDA receptors, including those containing GluN2D, and are used in clinical and research settings[2]. Safety considerations include central nervous system effects and the potential for manifesting or worsening seizures with both loss- and gain-of-function NMDA receptor mutations[2].

Other names

Glutamate receptor ionotropic, NMDA 2DGluN2DNMDAR2DNR2DEB11Glutamate [NMDA] receptor subunit epsilon-4N-methyl D-aspartate receptor subtype 2DN-methyl-D-aspartate receptor subunit 2Dglutamate receptor, ionotropic, NMDA 2Destrogen receptor binding CpG island

NMDA receptor antagonist (e.g., memantine, ketamine, dextromethorphan: non-competitive/uncompetitive pore blocking) Modulation of synaptic currents and neuronal excitability via ion channel block