Glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) (GRIN2A)

Glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) is a critical component of the N-methyl-D-aspartate (NMDA) receptor, a ligand-gated ion channel essential for excitatory neurotransmission and synaptic plasticity in the central nervous system (UniProt Q12879). The GRIN2A gene encodes the GluN2A subunit, which, along with GluN1 and other GluN2 subunits, forms heterotetrameric complexes that mediate calcium influx and downstream signaling pathways involved in learning and memory (NCBI Gene 2903). In the adult brain, GluN2A-containing receptors become the predominant NMDA receptor subtype at synapses, influencing the threshold for long-term potentiation and depression. Mutations in GRIN2A are strongly associated with a spectrum of neurodevelopmental disorders, particularly the epilepsy-aphasia spectrum, which includes Landau-Kleffner syndrome and Rolandic epilepsy (PubMed 23913003). Pharmacological targeting of GRIN2A involves both antagonists like memantine for gain-of-function mutations and positive allosteric modulators (PAMs) for loss-of-function variants. Furthermore, the GRIN2A mRNA is an emerging target for precision therapies, such as antisense oligonucleotides (ASOs), designed to modulate protein expression levels in patients with specific genetic etiologies (PubMed 31511562).

Other names

GluN2ANMDAR2ANR2AGrin2a mRNALPOFFEVFEPKSGlutamate receptor ionotropic, NMDA 2A

Non-competitive NMDA receptor antagonism, positive allosteric modulation, and transcript-level modulation via antisense oligonucleotides.