NMDA receptors are a class of ionotropic glutamate receptors. The receptors are clustered at postsynaptic membranes of neurons and are composed of four subunits, which form a pore that allows for the passage of cations, including Ca2+, Na+, and K+. Normally, the pore of the receptor is blocked by Mg2+ in a voltage-dependent manner. Activation of the receptor requires binding of its main agonist, glutamate, as well as its co-agonist, glycine. Upon binding of glutamate and glycine and depolarization of the postsynaptic membrane mediated by another type of ionotropic receptor, AMPA receptor, Mg2+-caused block is relieved. This allows for the passage of Ca2+ and Na+ inside and K+ outside the cell, which leads to further postsynaptic membrane depolarization and activation of multiple downstream signaling pathways. Normal function of NMDA receptors is crucial for neuronal development, synaptic plasticity, learning, and memory. NMDA receptor is composed of four subunits assembled from seven possible ones (GluN1, GluN2 A to D, and GluN3A and GluN3B). A conventional NMDA receptor includes two GluN1 and two GluN2 subunits. The role of another type of subunits, GluN3, is not yet clear, although both its subtypes (GluN3A and GluN3B) were shown to resemble GluN1 subunits structurally and to assemble with the latter forming a functional receptor. Subunits of NMDA receptor are encoded by<unk>  genes: *<unk> 1 codes for GluN1; *<unk> 2A,<unk> 2B,<unk> 2C, and<unk> 2D code for GluN2 A to D; *<unk> 3A and<unk> 3B code for GluN3A and GluN3B. Missense and nonsense variants of these genes can affect the function of the NMDA receptor and potentially lead to a range of neurological and neuropsychiatric sequelae. Variants in<unk> 1,<unk> 2A,<unk> 2B, and<unk> 2D were shown to be associated with specific clinical syndromes.
GRIN disorder
SYT1-associated neurodevelopmental disorder
Krabbe disease
CADASIL
Foster Kennedy syndrome
Poland syndrome
MECP2 duplication syndrome
Sandhoff disease