GRIN2D Gene: NMDA Receptor Subunit 2D - Function, Mutations & Related Diseases

GRIN2D encodes the GluN2D subunit of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor that mediates excitatory neurotransmission. The GluN2D subunit is predominantly expressed in the brain, particularly in the thalamus, hippocampus, and brainstem, and plays a critical role in synaptic plasticity, neuronal development, and excitotoxicity. Mutations in GRIN2D are associated with neurodevelopmental disorders including epilepsy, intellectual disability, and autism spectrum disorder.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• NMDA receptor signaling (Reactome: R-HSA-438066)

• Unblocking of NMDA receptor

• glutamate binding and activation (Reactome: R-HSA-438064)

• Neurotransmitter receptor binding and downstream transmission in the postsynaptic cell (Reactome: R-HSA-112314)

The GluN2D protein (UniProt O15399) is a 1,336-amino acid subunit of the NMDA receptor. It contains an extracellular N-terminal domain, a ligand-binding domain, three transmembrane helices (M1, M3, M4), a re-entrant pore loop (M2), and an intracellular C-terminal domain. GluN2D assembles with GluN1 subunits to form functional NMDA receptors that are permeable to calcium ions. The C-terminal domain interacts with scaffolding proteins such as PSD-95 and mediates receptor trafficking and signaling.