GRIN2B — NMDA Receptor Subunit 2B

GRIN2B — NMDA Receptor Subunit 2B

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GRIN2B — NMDA Receptor Subunit 2B</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>GRIN2B</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>GRIN2B — NMDA Receptor Subunit 2B</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=GRIN2B" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/bipolar" style="color:#ef9a9a">BIPOLAR</a>, <a href="/wiki/bipolar" style="color:#ef9a9a">Bipolar</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">72 edges</a></td>
</tr>
</table>

Overview

GRIN2B — NMDA Receptor Subunit 2B

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GRIN2B — NMDA Receptor Subunit 2B</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>GRIN2B</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>GRIN2B — NMDA Receptor Subunit 2B</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=GRIN2B" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/bipolar" style="color:#ef9a9a">BIPOLAR</a>, <a href="/wiki/bipolar" style="color:#ef9a9a">Bipolar</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">72 edges</a></td>
</tr>
</table>

Overview

GRIN2B (Glutamate Ionotropic Receptor NMDA Type Subunit 2B) encodes the GluN2B subunit of the [NMDA receptor](/entities/nmda-receptor), a glutamate-gated calcium channel critical for synaptic plasticity, learning, and memory. The NMDA receptor complex requires both GRIN1 (GluN1) and GRIN2 (GluN2A-D) subunits for functional channels. GRIN2B is predominantly expressed during early development and persists in certain brain regions including the forebrain, [hippocampus](/brain-regions/hippocampus), and [cortex](/brain-regions/cortex)[@traynelis2010].

Function

The GRIN2B subunit contributes to the unique pharmacological and biophysical properties of NMDA receptors:

• Calcium Permeability: NMDA receptors containing GRIN2B have high calcium permeability, enabling calcium-dependent signaling cascades essential for synaptic plasticity[@paoletti2013]
• Slower Kinetics: GRIN2B-containing receptors have slower deactivation kinetics compared to GRIN2A-containing receptors
• Developmental Regulation: GRIN2B expression peaks early in development and decreases with age as GRIN2A expression increases
• Synaptic Localization: GRIN2B is primarily found at extrasynaptic and immature synapses

Role in Neurodegenerative Diseases

Alzheimer's Disease

GRIN2B dysfunction contributes to Alzheimer's disease pathogenesis through multiple mechanisms:

• Synaptic Dysfunction: [Aβ](/proteins/amyloid-beta) oligomers directly interact with NMDA receptors, causing internalization and impairment of glutamatergic signaling[@liu2021]
• Excitotoxicity: Altered GRIN2B function contributes to calcium dysregulation and excitotoxic cell death[@hynd2004]
• Memory Deficits: NMDA receptor hypofunction, particularly involving GRIN2B, correlates with cognitive deficits in AD
• [Tau](/proteins/tau) Pathology: Hyperphosphorylated [tau](/proteins/tau) disrupts GRIN2B signaling and NMDA receptor trafficking

Parkinson's Disease

• Dopaminergic Modulation: GRIN2B-containing NMDA receptors are modulated by dopamine in the striatum
• Excitotoxicity: Overactivation of NMDA receptors contributes to dopaminergic neuron death
• Levodopa-Induced Dyskinesia: Enhanced GRIN2B signaling is implicated in L-DOPA-induced dyskinesias[@carmo2019]

ALS

• Motor Neuron Vulnerability: GRIN2B dysfunction contributes to excitotoxicity in motor [neurons](/entities/neurons)
• Glutamate Transport: Altered NMDA receptor signaling affects glutamate homeostasis

Therapeutic Implications

Drug Development

• GRIN2B Modulators: Positive allosteric modulators targeting GRIN2B are being developed for cognitive enhancement
• NMDA Receptor Antagonists: Memantine, an NMDA receptor antagonist, is approved for AD treatment
• Synaptic Protection: Maintaining proper GRIN2B function may protect against neurodegeneration

Research Directions

• Genetic Studies: GRIN2B polymorphisms have been associated with risk for various neuropsychiatric disorders
• Biomarkers: GRIN2B expression changes may serve as biomarkers for disease progression
• Gene Therapy: Viral vector delivery of GRIN2B modulators is being explored

Expression Patterns

GRIN2B shows region-specific expression:

• High Expression: Hippocampus (CA1, dentate gyrus), cerebral cortex (layers II-III, V), striatum
• Moderate Expression: Thalamus, olfactory bulb
• Cellular Localization: Neuronal cell bodies, [dendritic spines](/cell-types/dendritic-spines), postsynaptic densities

Interactions

GRIN2B interacts with numerous proteins:

• PSD-95: Anchors GRIN2B at postsynaptic densities
• CaMKII: Calcium/calmodulin-dependent kinase II phosphorylates GRIN2B
• SRC: Fyn kinase phosphorylates GRIN2B
• MAGUK Proteins: SAP90/PSD-95 family proteins

Molecular Mechanisms

NMDA Receptor Physiology

GRIN2B encodes the GluN2B subunit[^6]:

• Channel Properties: High calcium permeability
• Mg2+ Block: Voltage-dependent magnesium block
• Kinase Regulation: Multiple phosphorylation sites
• Splice Variants: Alternative splicing generates isoforms

Synaptic Plasticity

Critical for learning and memory:

• LTP Induction: Essential for long-term potentiation
• LTD Induction: Mediates long-term depression
• Homeostatic Plasticity: Adjusts synaptic strength
• Calcium Signaling: Triggers downstream cascades

See Also

• [NMDA Receptor](/entities/nmda-receptor)
• [Glutamate Excitotoxicity](/mechanisms/glutamate-excitotoxicity)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
• [Synaptic Plasticity](/mechanisms/synaptic-plasticity)

External Links

• [GRIN2B Gene - NCBI](https://www.ncbi.nlm.nih.gov/gene/2904)
• [GRIN2B - UniProt](https://www.uniprot.org/uniprot/Q03364)
• [Human Protein Atlas](https://www.proteinatlas.org/ENSG00000150045-GRN2B)

Brain Atlas Resources

Explore gene expression and cell type data for GRIN2B in these authoritative brain atlas resources:

• [Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=GRIN2B): Gene expression data from adult human brain specimens
• [Allen Cell Type Atlas](https://celltypes.brain-map.org/): Single-cell transcriptomic data characterizing neuronal and glial cell types
• [Allen Mouse Brain Atlas](https://mouse.brain-map.org/): Gene expression throughout the mouse brain
• [BrainSpan Atlas of the Developing Human Brain](https://www.brainspan.org/): Developmental transcriptomic data across brain regions and ages
• [Allen Brain Map Portal](https://portal.brain-map.org/): Unified access to all Allen Brain Atlas data resources

References

Pathway Diagram

The following diagram shows the key molecular relationships involving GRIN2B — NMDA Receptor Subunit 2B discovered through SciDEX knowledge graph analysis: