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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GRIK4
glutamate ionotropic receptor kainate type subunit 4
Chromosome 11 · 11q23.3
NCBI Gene: 2900Ensembl: ENSG00000149403.14HGNC: HGNC:4582UniProt: A0A8D9PH79
43PubMed Papers
20Diseases
4Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelReceptorTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potentialkainate selective glutamate receptor complexkainate selective glutamate receptor activitysynaptic transmission, glutamatergicepilepsymigraine disorderalcohol dependenceSeizure
✦AI Summary

GRIK4 encodes a kainate-type ionotropic glutamate receptor subunit (KA1) that functions as part of a cation-permeable ligand-gated ion channel. The protein cannot form functional channels independently but requires heteromeric assembly with other kainate receptor subunits (GRIK1, GRIK2, and GRIK3) to exhibit channel activity 1. KA1 protein is expressed in specific neuronal populations throughout the brain, including the cerebellum, frontal and parahippocampal cortices, and hippocampus, with particularly strong expression in CA3 and CA2 pyramidal cells and dentate gyrus granule cells 2. Functionally, GRIK4 plays a critical role in synaptic transmission and plasticity, with gene dosage alterations significantly affecting circuit output and behavior 3. Overexpression of GRIK4 enhances synaptic transmission, causing imbalanced inhibitory and excitatory activity that manifests as autism spectrum disorder-like behaviors including social impairment, enhanced anxiety, and depressive states 4. The gene shows clinical significance in psychiatric disorders, with specific polymorphisms associated with antidepressant treatment response in major depressive disorder 5 6 and copy number variations linked to autism 3. Additionally, a deletion variant in GRIK4 is associated with reduced bipolar disorder risk and increased protein expression 2.

Sources cited
1
GRIK4 cannot form functional channels independently
PMID: 8263508
2
KA1 protein expression patterns in human brain and association with bipolar disorder risk variant
PMID: 22052594
3
Gene dosage effects on synaptic transmission and circuit output
PMID: 29949767
4
Overexpression causes autism spectrum disorder-like behaviors
PMID: 26446216
5
Association with venlafaxine treatment response in major depressive disorder
PMID: 31083176
6
GRIK4 polymorphisms associated with antidepressant treatment response
PMID: 25303296
Disease Associationsⓘ20
epilepsyOpen Targets
0.61Moderate
migraine disorderOpen Targets
0.59Moderate
alcohol dependenceOpen Targets
0.56Moderate
SeizureOpen Targets
0.56Moderate
Lennox-Gastaut syndromeOpen Targets
0.49Moderate
mathematical abilityOpen Targets
0.43Moderate
obesityOpen Targets
0.40Moderate
partial epilepsyOpen Targets
0.38Weak
HeadacheOpen Targets
0.37Weak
bipolar disorderOpen Targets
0.36Weak
cocaine dependenceOpen Targets
0.36Weak
PainOpen Targets
0.34Weak
Tourette syndromeOpen Targets
0.32Weak
subarachnoid hemorrhageOpen Targets
0.32Weak
occlusion precerebral arteryOpen Targets
0.32Weak
strokeOpen Targets
0.32Weak
nicotine dependenceOpen Targets
0.32Weak
COVID-19Open Targets
0.32Weak
pituitary gland diseaseOpen Targets
0.30Weak
Abruptio PlacentaeOpen Targets
0.30Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets4
SELURAMPANELPhase II
Glutamate receptor ionotropic AMPA antagonist
epilepsy
TEZAMPANELPhase II
Glutamate receptor ionotropic kainate antagonist
Pain
TEZAMPANEL ANHYDROUSPhase II
Glutamate receptor ionotropic kainate antagonist
Pain
TOPIRAMATEApproved
Glutamate receptor ionotropic AMPA antagonist
epilepsy
Related Genes
DLG4Protein interaction98%MARK4Protein interaction87%GRIK1Protein interaction85%C1QL3Protein interaction80%CACNG2Protein interaction80%GRIA4Protein interaction79%
Tissue Expression6 tissues
Ovary
100%
Brain
82%
Lung
33%
Heart
11%
Liver
2%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
GRIK4DLG4MARK4GRIK1C1QL3CACNG2GRIA4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q16099
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.59Moderately Constrained
pLIⓘ
0.04Tolerant
Observed/Expected LoF0.43 [0.33–0.59]
RankingsWhere GRIK4 stands among ~20K protein-coding genes
  • #9,738of 20,598
    Most Researched43
  • #1,009of 1,025
    FDA-Approved Drug Targets1
  • #3,966of 17,882
    Most Constrained (LOEUF)0.59 · top quartile
Genes detectedGRIK4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
PMID: 28600779
Hum Genet · 2017
1.00
2
Increased Grik4 Gene Dosage Causes Imbalanced Circuit Output and Human Disease-Related Behaviors.
PMID: 29949767
Cell Rep · 2018
0.90
3
GRIK4 and GRM7 gene may be potential indicator of venlafaxine treatment reponses in Chinese of Han ethnicity.
PMID: 31083176
Medicine (Baltimore) · 2019
0.80
4
GRIK4/KA1 protein expression in human brain and correlation with bipolar disorder risk variant status.
PMID: 22052594
Am J Med Genet B Neuropsychiatr Genet · 2012
0.70
5
GRIK4 polymorphism and its association with antidepressant response in depressed patients: a meta-analysis.
PMID: 25303296
Pharmacogenomics · 2014
0.60