GRIN2C Gene - Glutamate Ionotropic Receptor NMDA Type Subunit 2C

GRIN2C Gene - Glutamate Ionotropic Receptor NMDA Type Subunit 2C

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GRIN2C Gene - Glutamate Ionotropic Receptor NMDA Type Subunit 2C</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>GRIN2C</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>GRIN2C - Glutamate Ionotropic Receptor NMDA Type Subunit 2C</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=GRIN2C" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Grin2C Gene Glutamate Ionotropic Receptor Nmda Type Subunit 2C is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

[@nmda]
[@dna]

Overview

GRIN2C encodes the NR2C (GluN2C) [NMDA](/entities/nmda-receptor) receptor subunit, forming calcium-permeable ion channels with unique pharmacological and physiological properties. The gene is located on chromosome 17q25.1 and encodes a 1,218 amino acid protein. NR2C-containing NMDA receptors are predominantly expressed in subcortical structures. [@kainate]

Function

NR2C-containing NMDA receptors exhibit: [@excitotoxicity]

GRIN2C Gene - Glutamate Ionotropic Receptor NMDA Type Subunit 2C

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GRIN2C Gene - Glutamate Ionotropic Receptor NMDA Type Subunit 2C</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>GRIN2C</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>GRIN2C - Glutamate Ionotropic Receptor NMDA Type Subunit 2C</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=GRIN2C" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Grin2C Gene Glutamate Ionotropic Receptor Nmda Type Subunit 2C is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

[@nmda]
[@dna]

Overview

GRIN2C encodes the NR2C (GluN2C) [NMDA](/entities/nmda-receptor) receptor subunit, forming calcium-permeable ion channels with unique pharmacological and physiological properties. The gene is located on chromosome 17q25.1 and encodes a 1,218 amino acid protein. NR2C-containing NMDA receptors are predominantly expressed in subcortical structures. [@kainate]

Function

NR2C-containing NMDA receptors exhibit: [@excitotoxicity]

• Reduced magnesium sensitivity: Altered voltage dependence
• Slow deactivation kinetics: Extended channel open times
• Calcium permeability: Important for signaling cascades
• Phencyclidine insensitivity: Distinct pharmacological profile

• Synaptic plasticity in cerebellar and thalamic circuits
• Sensory processing, particularly auditory pathways
• Motor coordination through basal ganglia modulation
• Developmental plasticity in the cerebellum

Disease Associations

Alzheimer's Disease (AD)

• GRIN2C expression reduced in AD cerebellum
• Loss of NR2C-containing receptors affects cerebellar plasticity
• May contribute to motor and coordination deficits
• Therapeutic modulation explored for cognitive effects

Parkinson's Disease (PD)

• Altered NMDA receptor composition in PD models
• NR2C function affects striatal plasticity
• Contributes to levodopa-induced dyskinesias
• NMDA antagonists modulate motor symptoms

Schizophrenia

• GRIN2C genetic variants linked to schizophrenia risk
• Altered receptor function affects glutamatergic signaling
• May contribute to cognitive deficits
• NMDA receptor modulators in clinical trials

Ataxia

• NR2C knockout mice show ataxic phenotype
• Cerebellar long-term depression impaired
• Motor learning deficits observed
• Channel represents therapeutic target

Hypoxic-Ischemic Injury

• NR2C-containing receptors mediate vulnerability
• Calcium influx through these channels contributes to damage
• Protective effects of NR2C antagonists

Expression Pattern

GRIN2C shows highest expression in:

• Cerebellar granule cells
• Thalamic relay [neurons](/entities/neurons)
• Olfactory bulb
• Basal ganglia (striatum, globus pallidus)
• Superior colliculus
• Spinal cord dorsal horn

Molecular Mechanisms

Channel Assembly

• Forms heterotetrameric receptors with GluN1
• Co-assembles with other NR2 subunits in some neurons
• Alternative splicing generates variants
• PDZ domain interactions anchor at synapses

Signaling Pathways

• Calcium influx activates CaMKII
• Coupling to MAPK/ERK pathway
• CREB-mediated gene expression
• Synaptic plasticity mechanisms

Regulation

• Phosphorylation by src family kinases
• Glycine/D-serine as co-agonists required
• Membrane trafficking regulated by MAGUK proteins
• Receptor internalization and recycling

Therapeutic Targeting

NMDA Receptor Modulators

• Ketamine: Non-competitive antagonist
• Memantine: Low-affinity voltage-dependent blocker
• D-cycloserine: Partial agonist at glycine site

NR2C-Selective Approaches

• ifenprodil: NR2B-selective antagonist
• CIQ: NR2C/D-selective positive modulator (experimental)
• CERC-610: NR2C-selective antagonist

Research Directions

• Allosteric modulators with subunit specificity
• Gene therapy for GRIN2C mutations
• Targeted delivery to specific brain regions
• Combination approaches with other NMDA subunits

Key Publications

See Also

• [NMDA Receptors](/entities/nmda-receptors)
• [Glutamatergic Signaling](/mechanisms/glutamatergic-signaling)
• [Calcium Signaling](/mechanisms/calcium-signaling)mechanisms/calcium-signaling-dysregulation)
• [Synaptic Plasticity](/mechanisms/synaptic-plasticity)
• [Cerebellar Ataxia](/diseases/cerebellar-ataxia)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [NCBI Gene: GRIN2C](https://www.ncbi.nlm.nih.gov/gene/2905)
• [UniProt: Q8TCU5](https://www.uniprot.org/uniprot/Q8TCU5)
• [OMIM: 138254](https://www.omim.org/entry/138254)
• [GeneCards: GRIN2C](https://www.genecards.org/cgi-bin/carddisp.pl?gene=GRIN2C)

Background

The study of Grin2C Gene Glutamate Ionotropic Receptor Nmda Type Subunit 2C has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References