protein
Glutamate receptor ionotropic, NMDA 2B
aka GluN2B
Gene
GRIN2B
Organism
Homo sapiens(9606)
Length
1484 aa
Mass
166,367 Da
# GRIN2B Summary
GRIN2B (also called GluN2B) is a subunit of N-methyl-D-aspartate (NMDA) receptors, which function as heterotetrameric ligand-gated calcium channels with voltage-dependent regulation by magnesium (UniProt: Q13224). The protein enables channel activation through coordinated binding of glutamate to GluN2B and glycine or D-serine to partner subunits, permitting calcium and sodium influx while potassium exits. Each GluN2 subunit confers distinct kinetic properties to the channel, modulating activation, deactivation, desensitization, and responsiveness to allosteric modulators.
GRIN2B participates in synaptic plasticity underlying learning and memory, particularly through long-term depression in the hippocampus. At extrasynaptic sites, it partners with DAPK1 to mediate excitotoxic calcium influx during stroke-related neuronal injury. The protein is implicated in intellectual developmental disorder, autosomal dominant 6 (MRD6; OMIM 613970), which features intellectual disability, seizures, and autistic features, and in developmental and epileptic encephalopathy 27 (DEE27; OMIM 616139).
GRIN2B carries SFARI Category 1 classification with syndromic autism annotation (SFARI Cat 1), indicating strong evidence for association with autism spectrum disorder, particularly in syndromic presentations accompanied by intellectual disability and seizures.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
High confidence — strong genetic evidence from multiple studies
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed:24272827, PubMed:24863970, PubMed:26875626, PubMed:26919761, PubMed:27839871, PubMed:28095420, PubMed:28126851, PubMed:38538865, PubMed:8768735). Participates in synaptic plasticity for learning and memory formation by contributing to the long-term depression (LTD) of hippocampus membrane currents (By similarity). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:24272827, PubMed:24863970, PubMed:26875626, PubMed:26919761, PubMed:27839871, PubMed:28095420, PubMed:28126851, PubMed:38538865, PubMed:8768735). NMDARs mediate simultaneously the potassium efflux and the influx of calcium and sodium (By similarity). Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (PubMed:26875626, PubMed:28095420, PubMed:28126851, PubMed:38538865, PubMed:8768735). In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity)
Disease associations
Intellectual developmental disorder, autosomal dominant 6, with or without seizuresMRD6
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD6 additional features may include seizures, hypotonia, abnormal movements, such as dystonia, and autistic features.
Developmental and epileptic encephalopathy 27DEE27
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent.
Sources
Last updated 5/6/2026, 5:25:36 AM