NR2C

NR2C, also known as the NMDA receptor subunit NR2C, is a subunit of the NMDA-type ionotropic glutamate receptor encoded by the GRIN2C gene. NMDA receptors are tetrameric channels typically composed of two NR1 subunits and two regulatory NR2 subunits (NR2A–D). When NR2C subunits assemble with NR1, they form functional receptors that mediate excitatory synaptic transmission and calcium influx in response to glutamate and the co-agonist glycine or D-serine.

Expression of NR2C is highest in the cerebellum, particularly in granule cells, with detectable expression in select thalamic nuclei and brainstem. In the mature brain, NR2C remains prominent in cerebellar circuits, while cortical expression is comparatively limited. The subunit contributes to the unique biophysical and pharmacological properties of the receptors it forms.

Biophysically, NR2C-containing NMDA receptors exhibit distinct kinetics and voltage dependence compared with receptors containing NR2A or NR2B. They tend to have slower deactivation and show different sensitivity to magnesium block and other modulators, which influences synaptic integration and plasticity in the circuits where they are expressed.

Clinical relevance includes associations between GRIN2C variants and neurodevelopmental conditions, including epilepsy, in rare cases. The evidence base is evolving, and the pathogenicity of specific variants remains under investigation. Pharmacologically, NR2C-containing receptors have a distinct profile from NR2A- or NR2B-rich receptors, and while NR2C-selective ligands have been described in preclinical work, there are no approved subunit-specific drugs targeting NR2C.