GRIN3

GRIN3 refers to the gene family that encodes the GluN3 subunits of NMDA-type ionotropic glutamate receptors. In humans, the two genes GRIN3A and GRIN3B encode the subunits commonly referred to as NR3A and NR3B. These subunits are part of the NMDA receptor complex, which is typically built from two GluN1 subunits and two GluN2 subunits. GluN3 subunits can co-assemble with GluN1 and GluN2 to form various NMDA receptor configurations, and they influence the receptor’s pharmacology and signaling properties.

Structure and function are linked to their modulatory role. GluN3A and GluN3B are transmembrane proteins with extracellular domains that interact with other receptor subunits. When incorporated into NMDA receptors, GluN3 subunits generally reduce calcium permeability and single-channel conductance and can alter voltage dependence and ligand sensitivity compared with receptors composed solely of GluN1 and GluN2. This modulation can occur in tri-heteromeric receptors containing GluN1, GluN2, and GluN3, contributing to diverse signaling outcomes across synapses.

Expression and development vary by subunit. GRIN3A and GRIN3B are expressed in the brain with region- and development-dependent patterns. GRIN3A tends to be prominent during certain developmental stages, while GRIN3B shows a distinct but broader distribution that can persist into adulthood.

Clinical and research relevance is ongoing. Genetic variation and altered expression of GRIN3A and GRIN3B have been explored in relation to neurodevelopmental and psychiatric conditions, including schizophrenia and autism spectrum disorders, but findings remain inconclusive and are an active area of investigation.