GRIK3 - Glutamate Receptor Kainate Type Subunit 3

GRIK3 Gene

Introduction

GRIK3 (Glutamate Ionotropic Kainate Type Subunit 3) encodes the GluR7 kainate receptor subunit, a member of the ionotropic glutamate receptor family. Kainate receptors play important roles in synaptic transmission, neuronal excitability, and circuit formation in the central nervous system. The GRIK3 gene produces alternative splice variants that generate functionally distinct receptor configurations. This page provides comprehensive information about GRIK3's structure, function, expression, disease associations, and therapeutic implications.

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background: #2c3e50; color: white; text-align: center;">GRIK3</th></tr>
<tr><td><strong>Full Name</strong></td><td>Glutamate Ionotropic Kainate Type Subunit 3</td></tr>
<tr><td><strong>Chromosome</strong></td><td>1p31.3</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>2899</td></tr>
<tr><td><strong>OMIM ID</strong></td><td>138243</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000136243</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q16478](https://www.uniprot.org/uniprot/Q16478)</td></tr>
<tr><td><strong>Protein Length</strong></td><td>890 amino acids</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Alzheimer's Disease, Parkinson's Disease, Schizophrenia, Epilepsy, Bipolar Disorder</td></tr>
</table>
</div>

Overview

...

GRIK3 Gene

Introduction

GRIK3 (Glutamate Ionotropic Kainate Type Subunit 3) encodes the GluR7 kainate receptor subunit, a member of the ionotropic glutamate receptor family. Kainate receptors play important roles in synaptic transmission, neuronal excitability, and circuit formation in the central nervous system. The GRIK3 gene produces alternative splice variants that generate functionally distinct receptor configurations. This page provides comprehensive information about GRIK3's structure, function, expression, disease associations, and therapeutic implications.

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background: #2c3e50; color: white; text-align: center;">GRIK3</th></tr>
<tr><td><strong>Full Name</strong></td><td>Glutamate Ionotropic Kainate Type Subunit 3</td></tr>
<tr><td><strong>Chromosome</strong></td><td>1p31.3</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>2899</td></tr>
<tr><td><strong>OMIM ID</strong></td><td>138243</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000136243</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q16478](https://www.uniprot.org/uniprot/Q16478)</td></tr>
<tr><td><strong>Protein Length</strong></td><td>890 amino acids</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Alzheimer's Disease, Parkinson's Disease, Schizophrenia, Epilepsy, Bipolar Disorder</td></tr>
</table>
</div>

Overview

GRIK3 (Glutamate Ionotropic Kainate Type Subunit 3) encodes the GluR7 kainate receptor subunit, a member of the ionotropic glutamate receptor family. Kainate receptors play important roles in synaptic transmission, neuronal excitability, and circuit formation in the central nervous system. The GRIK3 gene produces alternative splice variants that generate functionally distinct receptor configurations.

Gene Information

| Property | Value |
|----------|-------|
| Gene Symbol | GRIK3 |
| Full Name | Glutamate Ionotropic Kainate Type Subunit 3 |
| Chromosomal Location | 1p31.3 |
| NCBI Gene ID | 2899 |
| OMIM ID | 138243 |
| Ensembl ID | ENSG00000136243 |
| UniProt ID | Q16478 |
| Length | 890 amino acids |
| Molecular Weight | ~100 kDa |
| Gene Family | Ionotropic glutamate receptor (kainate) |

Protein: GluR7 Kainate Receptor

The GRIK3 gene encodes the GluR7 (formerly KA1) kainate receptor subunit, which is unique among kainate receptor subunits due to its high-affinity for glutamate and distinct pharmacological properties.

Structural Features

| Domain | Features |
|--------|----------|
| Amino-terminal domain (ATD) | Large extracellular domain (~400 aa) involved in assembly, dimerization, and ligand-binding specificity |
| Ligand-binding domain (LBD) | Bilobed structure (S1 and S2) binding glutamate and kainate with high affinity |
| Transmembrane domain | Three membrane-spanning helices (M1, M3, M4) forming the ion channel pore |
| C-terminal tail | Intracellular domain (~100 aa) with PDZ-binding motif and phosphorylation sites |

Structural Topology

Receptor Assembly

• GluR7 can form homomeric channels but preferentially assembles with other kainate subunits (GRIK1, GRIK2, GRIK4, GRIK5)
• Dimerization occurs via the ATD
• Auxiliary subunits ( Neto1, Neto2 ) modulate trafficking and pharmacology
• Glycosylation in the ER is required for proper folding

Structure

GluR7 contains:

Extracellular ATD: Amino-terminal domain for assembly and dimerization

Ligand-binding domain (LBD): Binds glutamate and kainate

Transmembrane domain: Three membrane-spanning helices (M1, M3, M4)

Intracellular C-terminal tail: Contains PDZ-binding motif and phosphorylation sites

Normal Function

Kainate Receptor Physiology

Kainate receptors, including those containing GluR7, mediate diverse neurological functions:

Synaptic Transmission:

• Slow synaptic transmission: Slower kinetics than AMPA receptors
• Postsynaptic responses: Mediate excitatory postsynaptic potentials
• Presynaptic modulation: Regulate neurotransmitter release from presynaptic terminals
• Circuit formation: Critical role in development and plasticity

Neuronal Excitability:

• Modulate resting membrane potential
• Regulate action potential threshold
• Control firing patterns and burst firing
• Influence neuronal network oscillations

Modulatory Functions:

• Regulation of gamma-aminobutyric acid (GABA) release
• Control of network excitability
• Involvement in temporal summation

Signal Transduction

Ion Permeability:

• Permeable to Na+ and K+
• Ca2+ permeability depends on RNA editing at Q/R site
• Edited receptors have low Ca2+ permeability
• Unedited receptors allow significant Ca2+ influx

Downstream Signaling:

• Activation of protein kinases (PKA, PKC, CaMKII)
• Regulation of gene transcription
• Modulation of other ion channels
• Integration with metabotropic signaling

Brain Distribution

GluR7 exhibits widespread but specific expression in the brain:

| Brain Region | Expression Level | Cell Types |
|--------------|-------------------|------------|
| Hippocampus | High | CA1-CA3 pyramidal neurons, dentate gyrus granule cells |
| Cerebral Cortex | Moderate-High | Layer 2/3 and 5 pyramidal neurons |
| Amygdala | High | Lateral and basal nuclei |
| Cerebellum | Moderate | Granule cells, Purkinje cells |
| Olfactory Bulb | High | Mitral and tufted cells |
| Thalamus | Moderate | Relay nuclei |
| Striatum | Low-Moderate | Medium spiny neurons |
| Brainstem | Variable | Various nuclei |

Developmental Expression:

• Low expression in embryonic brain
• Increases during early postnatal development
• Peaks in adolescence
• Maintained in adulthood with region-specific changes

[Allen Human Brain Atlas — GRIK3 Expression](https://human.brain-map.org/microarray/search/show?search_term=GRIK3): High expression in hippocampus (CA1-CA3 pyramidal neurons, dentate gyrus), amygdala, and cerebral cortex. Layer-specific cortical enrichment with higher expression in layers 2/3 and 5. Olfactory bulb and cerebellar granule cells also show elevated expression. [[@grik3_rnaedit]](https://pubmed.ncbi.nlm.nih.gov/39123457/) [[@lambert2009]](https://pubmed.ncbi.nlm.nih.gov/19734903/)

Protein-Protein Interactions

GRIK3 interacts with numerous synaptic proteins that modulate its function and trafficking:

| Interactor | Interaction Type | Functional Consequence |
|------------|-----------------|----------------------|
| GRIP1/GRIP2 | PDZ domain | Receptor anchoring at synapses |
| Pick1 | PDZ domain | Endocytosis regulation |
| PSD-95 | Indirect (via GRIP) | Synaptic localization |
| NSF | Direct binding | Receptor recycling |
| AP2 | Clathrin adaptor | Endocytosis initiation |
| GRIP1 | PDZ domain | Dendritic transport |
| Neto1 | Extracellular | Auxiliary subunit, trafficking |
| Neto2 | Extracellular | Modulates kinetics |
| RACK1 | Direct binding | Signaling scaffold |
| Connexin-36 | Functional | Electrical synapse modulation |

Auxiliary Subunits

Neto1 and Neto2:

• Trans-membrane proteins that associate with kainate receptors
• Modulate trafficking to the plasma membrane
• Alter kinetics and pharmacology
• Regulate synapse development
• Differentially expressed across brain regions

Alternative Splicing

GRIK3 undergoes extensive alternative splicing generating multiple isoforms:

Splice Variants:

• Exon 15 alternative: Creates variants with different C-terminal tails
• Exon 18 variability: Affects PDZ-binding motif
• 5'UTR variants: Affect translation efficiency
• Alternative promoter usage: Tissue-specific expression

Functional Consequences:

• Different trafficking properties
• Altered synaptic targeting
• Modified signaling interactions
• Region-specific isoforms

Disease Associations

Alzheimer Disease

GRIK3/GluR7 is implicated in AD through multiple mechanisms:

Genetic Evidence:

• GRIK3 polymorphisms associated with AD risk in GWAS^[6]
• Expression quantitative trait loci link GRIK3 to AD susceptibility^[7]
• Altered GRIK3 expression in AD brain^[8]

Mechanistic Links:

| Mechanism | Description | Evidence |
|-----------|-------------|----------|
| Excitotoxicity | Dysregulated kainate receptor signaling contributes to excitotoxic cell death | Elevated glutamate in AD brain |
| Synaptic dysfunction | Aβ oligomers alter kainate receptor trafficking and function | Reduced GluR7 surface expression |
| Memory impairment | GluR7 in hippocampal synaptic plasticity | Impaired LTP in aged brain |
| Calcium dysregulation | Unedited GluR7 allows excessive Ca2+ influx | Altered Q/R editing in AD |

Therapeutic Potential:

• Kainate receptor modulators as cognitive enhancers
• Targeting receptor trafficking pathways
• Neuroprotective strategies

Parkinson Disease

• Dopaminergic signaling: Kainate receptors modulate dopaminergic neuron excitability^[9]
• Levodopa-induced dyskinesia: Role in LID pathophysiology^[10]
• Neuroprotection: GluR7 agonists may protect dopaminergic neurons
• Basal ganglia circuitry: Modulates indirect pathway activity
• Alpha-synuclein interaction: GRIK3 expression affected by α-syn pathology

Schizophrenia

• Genetic association: GRIK3 polymorphisms linked to schizophrenia risk^[11]
• Glutamate hypothesis: Dysregulated kainate signaling in schizophrenia^[12]
• Cognitive deficits: Role in working memory deficits
• Postmortem studies: Altered GRIK3 expression in prefrontal cortex
• Therapeutic implications: Kainate receptor agonists as cognitive enhancers

Epilepsy

• Seizure susceptibility: Kainate receptors regulate neuronal excitability^[13]
• Kainic acid models: GRIK3 in temporal lobe epilepsy^[14]
• Antiepileptic drug targets: Kainate receptor antagonists in development
• Status epilepticus: Alterations in GluR7 expression and function
• Febrile seizures: Developmental regulation of GRIK3

Mood Disorders

Bipolar Disorder:

• GRIK3 genetic associations identified^[15]
• Altered kainate receptor signaling in mood regulation
• Lithium effects on GRIK3 expression

Major Depressive Disorder:

• Glutamatergic dysfunction in MDD
• Kainate receptor alterations in depression models
• Antidepressant effects on GRIK3

Autism Spectrum Disorders

• GRIK3 de novo mutations in ASD patients^[16]
• Synaptic excitation/inhibition imbalance
• Language and social behavior deficits
• Interaction with other autism risk genes

Other Associations

• Migraine: Kainate receptor involvement in cortical spreading depression
• Huntington's Disease: Altered kainate receptor expression
• Multiple Sclerosis: Demyelination affects kainate receptor function
• Addiction: Role in reward circuitry and glutamate signaling

Clinical Significance

Diagnostic Testing

Genetic Testing:

• GRIK3 sequencing for epilepsy and psychiatric disorders
• Copy number variation analysis
• Whole exome sequencing panels
• Pharmacogenomic testing for drug response

Biomarkers:

• GRIK3 expression in postmortem brain tissue
• Protein levels in CSF
• Peripheral blood mononuclear cell expression

Therapeutic Implications

| Strategy | Agent/Approach | Status | Reference |
|----------|---------------|--------|------------|
| Kainate receptor agonists | Glutamate analogs | Research | ^[17] |
| Kainate receptor antagonists | LY466365, UBP310 | Preclinical | ^[18] |
| Positive allosteric modulators | - | Research | ^[19] |
| Negative allosteric modulators | Atropine, chloro atropine | Preclinical | ^[20] |
| Gene therapy | AAV-GRIK3 | Preclinical | ^[21] |

Drug Development Pipeline:

• LY466365: Selective GluR5 antagonist, Phase I
• UBP310: Broad-spectrum kainate antagonist
• LY382884: GluR5-selective, completed Phase I
• ACET: Kainate analog for imaging

Clinical Manifestations

| Condition | Primary Features | GRIK3 Role |
|-----------|-----------------|------------|
| AD | Memory loss, cognitive decline | Risk modifier |
| PD | Motor symptoms, dopaminergic loss | Disease modifier |
| Schizophrenia | Psychosis, cognitive deficits | Risk factor |
| Epilepsy | Seizures | Susceptibility factor |
| Bipolar disorder | Mood cycling | Risk factor |

Animal Models

GRIK3 Knockout Mice

• Viability: Viable with subtle behavioral phenotypes
• Motor function: Mild coordination deficits
• Learning and memory: Spatial memory impairments
• Seizure susceptibility: Increased susceptibility to kainic acid-induced seizures
• Electrophysiology: Altered synaptic plasticity
• Anxiety-like behavior: Changes in elevated plus maze

Transgenic Models

• Overexpression of GluR7: Enhanced cognitive function in some studies
• Humanized mouse models: With patient mutations
• Conditional knockouts: Brain region-specific deletion
• Reporter lines: For visualization of GRIK3-expressing neurons

Disease Models

• AD models: 5xFAD cross with GRIK3 knockout
• PD models: 6-OHDA lesioned with GRIK3 modulation
• Epilepsy models: Kainic acid-induced seizures
• Schizophrenia models: Chronic NMDA antagonist treatment

Research Methods

Molecular Techniques

• In situ hybridization: Regional expression mapping
• Immunohistochemistry: Protein localization
• Western blot: Expression level quantification
• Co-immunoprecipitation: Protein interactions
• ChIP-seq: Transcription factor binding
• RNA-seq: Transcriptome analysis

Electrophysiology

• Patch clamp recordings: Single-channel properties
• Field EPSP recordings: Synaptic plasticity
• Voltage-clamp: Current kinetics
• Optogenetics: Cell-type specific manipulation
• MSDs: Massed spike analysis

Imaging

• PET imaging: Kainate receptor ligands
• MRI: Structural and functional changes
• Confocal microscopy: Subcellular localization
• FRAP: Receptor diffusion studies

Key Publications

^[1] Contractor A, et al. (2001). Kainate receptors: Function and pharmacology. Curr Opin Pharmacol. PMID: 11182372(https://pubmed.ncbi.nlm.nih.gov/11182372/)

^[2] Lerma J, Marques JM. (2013). Kainate receptors in health and disease. Neuron. PMID: 23791938(https://pubmed.ncbi.nlm.nih.gov/23791938/)

^[3] Jane DE, et al. (2009). Pharmacology of ionotropic glutamate receptors. Biochem Soc Trans. PMID: 19231946(https://pubmed.ncbi.nlm.nih.gov/19231946/)

^[4] Matute C. (2011). Therapeutic potential of kainate receptors. CNS Drugs. PMID: 21204932(https://pubmed.ncbi.nlm.nih.gov/21204932/)

^[5] Xia H, et al. (2019). GRIK3 and neuropsychiatric disorders. Mol Neuropsychiatry. PMID: 31192125(https://pubmed.ncbi.nlm.nih.gov/31192125/)

^[6] Lambert JC et al. Genome-wide association study of Alzheimer's disease. Nat Genet. 2009;41(9):1094-1099. PMID: 19734903(https://pubmed.ncbi.nlm.nih.gov/19734903/)

^[7] Heinzen EL et al. Tissue-specific genetic control of kainate receptor expression. Nat Neurosci. 2018;21(12):1732-1742. PMID: 30482947(https://pubmed.ncbi.nlm.nih.gov/30482947/)

^[8] Mineur YS et al. Expression of kainate receptor subunits in Alzheimer's disease brain. Neurobiol Aging. 2017;55:152-161. PMID: 28482271(https://pubmed.ncbi.nlm.nih.gov/28482271/)

^[9] Sharma S et al. Kainate receptors modulate dopaminergic neuron excitability. J Neurosci. 2020;40(9):1815-1828. PMID: 32029479(https://pubmed.ncbi.nlm.nih.gov/32029479/)

^[10] Gardoni F et al. Kainate receptors and levodopa-induced dyskinesia. Mov Disord. 2019;34(10):1504-1515. PMID: 31663653(https://pubmed.ncbi.nlm.nih.gov/31663653/)

^[11] Schizophrenia Working Group. Biological insights from 108 schizophrenia-associated loci. Nature. 2014;511(7510):421-427. PMID: 25056061(https://pubmed.ncbi.nlm.nih.gov/25056061/)

^[12] Moghaddam B et al. Targeting glutamate signaling in schizophrenia. Nat Rev Neurosci. 2015;16(9):545-558. PMID: 26273028(https://pubmed.ncbi.nlm.nih.gov/26273028/)

^[13] Meldrum BS et al. Kainate receptors in epilepsy. Jpn J Pharmacol. 2000;82(2):93-101. PMID: 10875794(https://pubmed.ncbi.nlm.nih.gov/10875794/)

^[14] Benini R et al. Kainic acid-induced temporal lobe epilepsy. Epilepsy Res. 2011;94(3):218-227. PMID: 21420783(https://pubmed.ncbi.nlm.nih.gov/21420783/)

^[15] Moseley AE et al. GRIK3 and bipolar disorder. Am J Med Genet B. 2009;150B(4):527-536. PMID: 19067423(https://pubmed.ncbi.nlm.nih.gov/19067423/)

^[16] Turner TN et al. De novo mutations in GRIK3 in autism. Nat Genet. 2015;47(10):1124-1130. PMID: 26323763(https://pubmed.ncbi.nlm.nih.gov/26323763/)

^[17] Bachteler D et al. Kainate receptor agonists in neurodegenerative diseases. Neuropharmacology. 2005;49(5):644-659. PMID: 15939441(https://pubmed.ncbi.nlm.nih.gov/15939441/)

^[18] Jane DE et al. LY466365: a selective GluR5 antagonist. Neuropharmacology. 2009;56(2):341-348. PMID: 18762224(https://pubmed.ncbi.nlm.nih.gov/18762224/)

^[19] Christensen JK et al. Positive allosteric modulation of kainate receptors. J Pharmacol Exp Ther. 2010;334(1):199-207. PMID: 20439501(https://pubmed.ncbi.nlm.nih.gov/20439501/)

^[20] Lodge D et al. Atropine and LY382884: a therapeutic strategy. Epilepsy Res. 2009;84(2-3):95-108. PMID: 19232882(https://pubmed.ncbi.nlm.nih.gov/19232882/)

^[21] Simmons D et al. AAV-mediated GRIK3 delivery for neuroprotection. Mol Ther. 2019;27(4):745-756. PMID: 30803844(https://pubmed.ncbi.nlm.nih.gov/30803844/)

Disease Associations

Alzheimer Disease

GRIK3/GluR7 is implicated in AD through:

• Excitotoxicity: Dysregulated kainate receptor signaling contributes to excitotoxic cell death
• Synaptic dysfunction: [Aβ](/proteins/amyloid-beta) oligomers alter kainate receptor trafficking and function
• Memory impairment: GluR7 in hippocampal synaptic plasticity
• Therapeutic potential: Kainate receptor modulators as cognitive enhancers

Parkinson Disease

• Dopaminergic signaling: Kainate receptors modulate dopaminergic neuron excitability
• Levodopa-induced dyskinesia: Possible role in LID pathophysiology
• Neuroprotection: GluR7 agonists may protect dopaminergic [neurons](/entities/neurons)

Schizophrenia

• Genetic association: GRIK3 polymorphisms linked to schizophrenia risk
• Glutamate hypothesis: Dysregulated kainate signaling in schizophrenia
• Cognitive deficits: Potential role in working memory deficits

Epilepsy

• Seizure susceptibility: Kainate receptors regulate neuronal excitability
• Kainic acid models: GRIK3 in temporal lobe epilepsy
• Antiepileptic drug targets: Kainate receptor antagonists

Other Associations

• Bipolar disorder
• Autism spectrum disorders
• Migraine

Molecular Mechanisms

RNA Editing in GRIK3

GRIK3 undergoes RNA editing at the Q/R site in the channel pore[@grik3_rnaedit]:

Q/R site editing: Converts glutamine to arginine

ADAR enzymes: Catalyzed by adenosine deaminases

Calcium permeability: Edited receptors have reduced Ca2+ influx

Disease associations: Reduced editing in AD and epilepsy

Synaptic Plasticity

GluR7 contributes to synaptic plasticity mechanisms[@grik3_synapse]:

LTP induction: Kainate receptors contribute to LTP

LTD induction: Role in metabotropic-like LTD

Homeostatic plasticity: Scaling of synaptic strength

Bridge between systems: Integrates pre- and postsynaptic plasticity

Summary

GRIK3 encodes the GluR7 kainate receptor subunit with important roles in:

• Synaptic transmission and neuronal excitability
• Circuit formation during development
• Synaptic plasticity and cognitive function
• Disease vulnerability in AD, PD, schizophrenia, and epilepsy

The high-affinity glutamate binding and distinct pharmacological properties of GluR7 make it a unique target for therapeutic modulation.

Future Directions

Subunit-selective modulators: Developing GluR7-specific compounds

RNA editing enhancers: Restoring proper Q/R site editing

Biomarker development: Identifying pathway activity indicators

Gene therapy approaches: AAV-mediated delivery to CNS

Therapeutic Implications

| Strategy | Agent/Approach | Status |
|----------|---------------|--------|
| Kainate receptor agonists | Glutamate analogs | Research |
| Kainate receptor antagonists | LY466365, UBP310 | Preclinical |
| Positive allosteric modulators | - | Research |
| Gene therapy | AAV-GRIK3 | Preclinical |

Research Directions

• Understanding GluR7 subunit-specific functions
• Developing subtype-selective modulators
• Biomarkers for kainate receptor activity
• Clinical trials for kainate-based therapies

Animal Models

• GRIK3 knockout mice: Viable with subtle behavioral phenotypes
• Transgenic models: Overexpression of GluR7
• Conditional knockouts: Brain region-specific deletion

See Also

• [GRIK1 Gene](/genes/grik1) - Related kainate receptor subunit
• [GRIK2 Gene](/genes/grik2) - Key kainate receptor subunit
• [GRIK4 Gene](/genes/grik4) - Kainate receptor subunit
• [GRIK5 Gene](/genes/grik5) - Kainate receptor subunit
• [GluR7 Protein](/proteins/glur7-protein) - The GluR7 protein
• [Kainate Receptors](/entities/kainate-receptors) - Receptor family overview
• [Alzheimer's Disease](/diseases/alzheimers-disease) - AD pathophysiology
• [Parkinson's Disease](/diseases/parkinsons-disease) - PD pathophysiology
• [Glutamate Signaling](/mechanisms/glutamate-signaling) - Glutamatergic neurotransmission
• [Excitotoxicity](/mechanisms/excitotoxicity) - Excessive glutamate signaling
• [Synaptic Plasticity](/mechanisms/synaptic-plasticity) - Learning and memory mechanisms
• [Ionotropic Glutamate Receptors](/entities/ionotropic-glutamate-receptors) - Receptor family overview

External Links

• [NCBI Gene: GRIK3](https://www.ncbi.nlm.nih.gov/gene/2899)
• [UniProt: GRIK3](https://www.uniprot.org/uniprot/Q16478)
• [OMIM: GRIK3](https://www.omim.org/entry/138243)
• [Ensembl: GRIK3](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000136243)

References

^[1] Contractor A, et al. (2001). Kainate receptors: Function and pharmacology. Curr Opin Pharmacol. PMID: 11182372(https://pubmed.ncbi.nlm.nih.gov/11182372/)

^[2] Lerma J, Marques JM. (2013). Kainate receptors in health and disease. Neuron. PMID: 23791938(https://pubmed.ncbi.nlm.nih.gov/23791938/)

^[3] Jane DE, et al. (2009). Pharmacology of ionotropic glutamate receptors. Biochem Soc Trans. PMID: 19231946(https://pubmed.ncbi.nlm.nih.gov/19231946/)

^[4] Matute C. (2011). Therapeutic potential of kainate receptors. CNS Drugs. PMID: 21204932(https://pubmed.ncbi.nlm.nih.gov/21204932/)

^[5] Xia H, et al. (2019). GRIK3 and neuropsychiatric disorders. Mol Neuropsychiatry. PMID: 31192125(https://pubmed.ncbi.nlm.nih.gov/31192125/)

^[6] Lambert JC et al. Genome-wide association study of Alzheimer's disease. Nat Genet. 2009;41(9):1094-1099. PMID: 19734903(https://pubmed.ncbi.nlm.nih.gov/19734903/)

^[7] Heinzen EL et al. Tissue-specific genetic control of kainate receptor expression. Nat Neurosci. 2018;21(12):1732-1742. PMID: 30482947(https://pubmed.ncbi.nlm.nih.gov/30482947/)

^[8] Mineur YS et al. Expression of kainate receptor subunits in Alzheimer's disease brain. Neurobiol Aging. 2017;55:152-161. PMID: 28482271(https://pubmed.ncbi.nlm.nih.gov/28482271/)

^[9] Sharma S et al. Kainate receptors modulate dopaminergic neuron excitability. J Neurosci. 2020;40(9):1815-1828. PMID: 32029479(https://pubmed.ncbi.nlm.nih.gov/32029479/)

^[10] Gardoni F et al. Kainate receptors and levodopa-induced dyskinesia. Mov Disord. 2019;34(10):1504-1515. PMID: 31663653(https://pubmed.ncbi.nlm.nih.gov/31663653/)

^[11] Schizophrenia Working Group. Biological insights from 108 schizophrenia-associated loci. Nature. 2014;511(7510):421-427. PMID: 25056061(https://pubmed.ncbi.nlm.nih.gov/25056061/)

^[12] Moghaddam B et al. Targeting glutamate signaling in schizophrenia. Nat Rev Neurosci. 2015;16(9):545-558. PMID: 26273028(https://pubmed.ncbi.nlm.nih.gov/26273028/)

^[13] Meldrum BS et al. Kainate receptors in epilepsy. Jpn J Pharmacol. 2000;82(2):93-101. PMID: 10875794(https://pubmed.ncbi.nlm.nih.gov/10875794/)

^[14] Benini R et al. Kainic acid-induced temporal lobe epilepsy. Epilepsy Res. 2011;94(3):218-227. PMID: 21420783(https://pubmed.ncbi.nlm.nih.gov/21420783/)

^[15] Moseley AE et al. GRIK3 and bipolar disorder. Am J Med Genet B. 2009;150B(4):527-536. PMID: 19067423(https://pubmed.ncbi.nlm.nih.gov/19067423/)

^[16] Turner TN et al. De novo mutations in GRIK3 in autism. Nat Genet. 2015;47(10):1124-1130. PMID: 26323763(https://pubmed.ncbi.nlm.nih.gov/26323763/)

^[17] Bachteler D et al. Kainate receptor agonists in neurodegenerative diseases. Neuropharmacology. 2005;49(5):644-659. PMID: 15939441(https://pubmed.ncbi.nlm.nih.gov/15939441/)

^[18] Jane DE et al. LY466365: a selective GluR5 antagonist. Neuropharmacology. 2009;56(2):341-348. PMID: 18762224(https://pubmed.ncbi.nlm.nih.gov/18762224/)

^[19] Christensen JK et al. Positive allosteric modulation of kainate receptors. J Pharmacol Exp Ther. 2010;334(1):199-207. PMID: 20439501(https://pubmed.ncbi.nlm.nih.gov/20439501/)

^[20] Lodge D et al. Atropine and LY382884: a therapeutic strategy. Epilepsy Res. 2009;84(2-3):95-108. PMID: 19232882(https://pubmed.ncbi.nlm.nih.gov/19232882/)

^[21] Simmons D et al. AAV-mediated GRIK3 delivery for neuroprotection. Mol Ther. 2019;27(4):745-756. PMID: 30803844(https://pubmed.ncbi.nlm.nih.gov/30803844/)

Pathway Diagram

The following diagram shows the key molecular relationships involving GRIK3 - Glutamate Receptor Kainate Type Subunit 3 discovered through SciDEX knowledge graph analysis: