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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
GRIK2
glutamate ionotropic receptor kainate type subunit 2
Chromosome 6 Β· 6q16.3
NCBI Gene: 2898Ensembl: ENSG00000164418.22HGNC: HGNC:4580UniProt: A0A8D9PH75
119PubMed Papers
22Diseases
4Drugs
13Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelReceptorTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
glutamate-gated receptor activityextracellularly glutamate-gated ion channel activityglutamate receptor signaling pathwayprotein bindingintellectual disability, autosomal recessive 6neurodevelopmental disorder with impaired language and ataxia and with or without seizuresSeizureepilepsy
✦AI Summary

GRIK2 encodes the GluR6 kainate receptor subunit, a glutamate-gated ion channel that mediates fast excitatory neurotransmission in the central nervous system 1. The gene undergoes complex alternative splicing, producing multiple transcript variants through cell-type-specific promoters that generate at least five different isoforms differing in their C-terminal domains and transmembrane regions 23. The neuronal promoter (GluR6A) is primarily expressed in brain tissue, while the non-neuronal promoter (GluR6B) is abundant in tumor cell lines, with differential methylation patterns regulating tissue-specific expression 3. Beyond its classical ionotropic glutamate receptor function, GRIK2 has been implicated in diverse physiological processes including muscle hypertrophy memory through epigenetic mechanisms 4. The gene shows disease associations with epilepsy, though linkage studies with idiopathic generalized epilepsies yielded negative results 5. However, GRIK2 represents a promising therapeutic target for mesial temporal lobe epilepsy, with gene therapy approaches using AAV9 vectors to reduce GRIK2 expression showing efficacy in reducing seizure frequency and improving cognitive function in preclinical models 6. Additionally, polymorphisms in GRIK2 have been associated with obsessive-compulsive disorder 7 and treatment-emergent suicidal events in depression 8.

Sources cited
1
GRIK2 encodes GluR6 kainate receptor mediating excitatory neurotransmission
PMID: 8034316
2
Gene produces multiple splice variants with different C-terminal and transmembrane domains
PMID: 11675011
3
Cell-type-specific promoters regulate tissue-specific expression through differential methylation
PMID: 35328043
4
GRIK2 involvement in muscle hypertrophy memory through epigenetic mechanisms
PMID: 29382913
5
No association found with idiopathic generalized epilepsies
PMID: 7675232
6
Gene therapy targeting GRIK2 shows promise for treating mesial temporal lobe epilepsy
PMID: 39429724
7
Polymorphisms associated with obsessive-compulsive disorder
PMID: 20370803
8
Association with treatment-emergent suicidal events in depression
PMID: 20504254
Disease Associationsβ“˜22
intellectual disability, autosomal recessive 6Open Targets
0.69Moderate
neurodevelopmental disorder with impaired language and ataxia and with or without seizuresOpen Targets
0.68Moderate
SeizureOpen Targets
0.64Moderate
epilepsyOpen Targets
0.61Moderate
migraine disorderOpen Targets
0.60Moderate
alcohol dependenceOpen Targets
0.56Moderate
complex neurodevelopmental disorderOpen Targets
0.51Moderate
Lennox-Gastaut syndromeOpen Targets
0.49Moderate
Intellectual disabilityOpen Targets
0.47Moderate
Hyperintensity of cerebral white matter on MRIOpen Targets
0.42Moderate
Severe global developmental delayOpen Targets
0.42Moderate
genetic disorderOpen Targets
0.41Moderate
obesityOpen Targets
0.40Moderate
Abnormality of the skeletal systemOpen Targets
0.39Weak
partial epilepsyOpen Targets
0.38Weak
HeadacheOpen Targets
0.37Weak
bipolar disorderOpen Targets
0.37Weak
autosomal recessive non-syndromic intellectual disabilityOpen Targets
0.37Weak
cocaine dependenceOpen Targets
0.36Weak
alcohol drinkingOpen Targets
0.35Weak
Intellectual developmental disorder, autosomal recessive 6UniProt
Neurodevelopmental disorder with impaired language and ataxia and with or without seizuresUniProt
Pathogenic Variants13
NM_021956.5(GRIK2):c.1969G>A (p.Ala657Thr)Pathogenic
Inborn genetic diseases|Neurodevelopmental disorder with impaired language and ataxia and with or without seizures|Gait ataxia;Intellectual disability;Severe global developmental delay|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 657
NM_021956.5(GRIK2):c.1567C>T (p.Arg523Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 523
NM_021956.5(GRIK2):c.126dup (p.Glu43Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 43
NM_021956.5(GRIK2):c.571G>T (p.Ala191Ser)Likely pathogenic
GRIK2-related disorder
β˜…β˜†β˜†β˜†2024β†’ Residue 191
NM_021956.5(GRIK2):c.1204-1G>TLikely pathogenic
Neurodevelopmental disorder with impaired language and ataxia and with or without seizures
β˜…β˜†β˜†β˜†2024
NM_021956.5(GRIK2):c.355C>T (p.Gln119Ter)Likely pathogenic
Neurodevelopmental disorder with impaired language and ataxia and with or without seizures
β˜…β˜†β˜†β˜†2023β†’ Residue 119
NM_021956.5(GRIK2):c.1960A>G (p.Asn654Asp)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 654
NM_021956.5(GRIK2):c.283+1G>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_021956.5(GRIK2):c.1979C>A (p.Thr660Lys)Pathogenic
GRIK2-related neurodevelopmental disorder|6 conditions|Neurodevelopmental disorder with impaired language and ataxia and with or without seizures
β˜…β˜†β˜†β˜†2018β†’ Residue 660
NM_021956.5(GRIK2):c.808C>T (p.Arg270Ter)Likely pathogenic
Intellectual disability
β˜…β˜†β˜†β˜†2018β†’ Residue 270
NM_021956.5(GRIK2):c.1979C>G (p.Thr660Arg)Pathogenic
Intellectual disability;Severe global developmental delay;Hyperintensity of cerebral white matter on MRI|Neurodevelopmental disorder with impaired language and ataxia and with or without seizures
β˜†β˜†β˜†β˜†2021β†’ Residue 660
NM_021956.5(GRIK2):c.2003T>C (p.Ile668Thr)Likely pathogenic
Autistic behavior
β˜†β˜†β˜†β˜†2021β†’ Residue 668
NM_021956.5(GRIK2):c.592C>T (p.Arg198Ter)Pathogenic
Intellectual disability, autosomal recessive 6
β˜†β˜†β˜†β˜†2015β†’ Residue 198
View on ClinVar β†—
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
PICK1Protein interaction100%GRIP1Protein interaction100%CNIH2Protein interaction99%PIAS3Protein interaction97%NETO1Protein interaction91%KLHL24Protein interaction85%
Tissue Expression6 tissues
Brain
100%
Heart
54%
Ovary
8%
Liver
6%
Lung
3%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
GRIK2PICK1GRIP1CNIH2PIAS3NETO1KLHL24
PROTEIN STRUCTURE
Preparing viewer…
PDB5CMM Β· 1.27 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.48Moderately Constrained
pLIβ“˜
0.99Intolerant
Observed/Expected LoF0.24 [0.13–0.48]
RankingsWhere GRIK2 stands among ~20K protein-coding genes
  • #3,962of 20,598
    Most Researched119 Β· top quartile
  • #930of 1,025
    FDA-Approved Drug Targets1
  • #2,585of 5,498
    Most Pathogenic Variants13
  • #2,770of 17,882
    Most Constrained (LOEUF)0.48 Β· top quartile
Genes detectedGRIK2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Alternative Promoters of
PMID: 35328043
Genes (Basel) Β· 2022
1.00
2
Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy.
PMID: 29382913
Sci Rep Β· 2018
0.90
3
Genomic organization of the human GRIK2 gene and evidence for multiple splicing variants.
PMID: 11675011
Gene Β· 2001
0.80
4
Association between polymorphisms in GRIK2 gene and obsessive-compulsive disorder: a family-based study.
PMID: 20370803
CNS Neurosci Ther Β· 2011
0.70
5
Refinement of map position of the human GluR6 kainate receptor gene (GRIK2) and lack of association and linkage with idiopathic generalized epilepsies.
PMID: 7675232
Neurology Β· 1995
0.60