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GRIK2 glutamate ionotropic receptor kainate type subunit 2 [ Homo sapiens (human) ]

Gene ID: 2898, updated on 3-Apr-2024

Summary

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Official Symbol
GRIK2provided by HGNC
Official Full Name
glutamate ionotropic receptor kainate type subunit 2provided by HGNC
Primary source
HGNC:HGNC:4580
See related
Ensembl:ENSG00000164418 MIM:138244; AllianceGenome:HGNC:4580
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
EAA4; GLR6; MRT6; GLUK6; GLUR6; GluK2; NEDLAS
Summary
Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. The subunit encoded by this gene is subject to RNA editing at multiple sites within the first and second transmembrane domains, which is thought to alter the structure and function of the receptor complex. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. Mutations in this gene have been associated with autosomal recessive cognitive disability. [provided by RefSeq, Jul 2008]
Expression
Biased expression in brain (RPKM 2.7), heart (RPKM 0.6) and 5 other tissues See more
Orthologs
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Genomic context

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Location:
6q16.3
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (101393708..102070083)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (102567441..103245122)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (101841584..102517958)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107984041 Neighboring gene NANOG hESC enhancer GRCh37_chr6:101399783-101400303 Neighboring gene mitogen-activated protein kinase 1 interacting protein 1 like pseudogene Neighboring gene small nucleolar RNA U13 Neighboring gene Sharpr-MPRA regulatory region 1689 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:101534194-101534783 Neighboring gene VISTA enhancer hs1738 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr6:101750186-101751385 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:101846362-101847246 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:101878111-101878612 Neighboring gene uncharacterized LOC101927388 Neighboring gene actin gamma 1 pseudogene 18 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:102062456-102063319 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:102164769-102165311 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:102189203-102189738 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:102521075-102522274 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:102554923-102555817 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:102555818-102556711 Neighboring gene uncharacterized LOC105377913 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_87080 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:102617347-102617964 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:102617965-102618581 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_87095 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_87198 Neighboring gene TARDBP pseudogene 5

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The Deletion of GluK2 Alters Cholinergic Control of Neuronal Excitability. Gorlewicz A, et al. Cereb Cortex, 2022 Jul 12. PMID 34730179
  2. Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders. Stolz JR, et al. Am J Hum Genet, 2021 Sep 2. PMID 34375587, Free PMC Article
  3. Correlation between GRIK2 rs6922753, rs2227283 polymorphism and aggressive behaviors with Bipolar Mania in the Chinese Han population. Ma H, et al. Brain Behav, 2019 Nov. PMID 31631587, Free PMC Article
  4. Interaction among GRIK2 gene on epilepsy susceptibility in Chinese children. Xiong S, et al. Acta Neurol Scand, 2019 Jun. PMID 30908586
  5. Isoforms of Ionotropic Glutamate Receptor GRIK2 Induce Senescence of Carcinoma Cells. Zhawar VK, et al. Cancer Genomics Proteomics, 2019 Jan-Feb. PMID 30587499, Free PMC Article

See all (106) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Epigenetic signature discriminates lymphatic metastasis in BRAF wild-type thyroid carcinoma: methylation role of GRIK2.
    Title: Epigenetic signature discriminates lymphatic metastasis in BRAF wild-type thyroid carcinoma: methylation role of GRIK2.
  2. The Deletion of GluK2 Alters Cholinergic Control of Neuronal Excitability.
    Title: The Deletion of GluK2 Alters Cholinergic Control of Neuronal Excitability.
  3. Kainate receptor modulation by NETO2.
    Title: Kainate receptor modulation by NETO2.
  4. Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders.
    Title: Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders.
  5. This study suggests that the rs2227283 polymorphism of the GRIK2 gene is related to aggressive behaviors in bipolar manic patients and that the A/A genotype and A allele may increase the risk of the aggressive behavior in bipolar manic patients.
    Title: Correlation between GRIK2 rs6922753, rs2227283 polymorphism and aggressive behaviors with Bipolar Mania in the Chinese Han population.
  6. Both the GRIK2 rs4840200-T and rs3213607-A, and the interactions between rs4840200 and rs9390754 are related to the increased risk of epilepsy risk.
    Title: Interaction among GRIK2 gene on epilepsy susceptibility in Chinese children.
  7. These results indicate involvement of GRIK2 in senescence and suggests GRIK2 as a potential target for therapeutic intervention of cancer cells.
    Title: Isoforms of Ionotropic Glutamate Receptor GRIK2 Induce Senescence of Carcinoma Cells.
  8. Study identifies differentially variable CpG sites in GRIK2 gene displaying increased expression in patients with chronic obstructive pulmonary disease.
    Title: Altered DNA methylation is associated with aberrant gene expression in parenchymal but not airway fibroblasts isolated from individuals with COPD.
  9. results suggest that PKC SUMOylation is an important regulator of the 14-3-3 and GluK2a protein complex and may contribute to regulate the decay kinetics of kainate receptor-excitatory postsynaptic currents
    Title: PKC SUMOylation inhibits the binding of 14-3-3τ to GluK2.
  10. these findings indicate that GRIK2 has a role in the maintenance of urothelial cancer stem cells and that GRIK2 and ALDH1 can be prognosis prediction markers for urinary tract carcinomas
    Title: GRIK2 has a role in the maintenance of urothelial carcinoma stem-like cells, and its expression is associated with poorer prognosis.
Submit: New GeneRIF Correction See all GeneRIFs (57)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Intellectual disability, autosomal recessive 6
MedGen: C1970198 OMIM: 611092 GeneReviews: Not available
Compare labs
Neurodevelopmental disorder with impaired language and ataxia and with or without seizures
MedGen: C5562006 OMIM: 619580 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortiu
EBI GWAS Catalog
Genome-wide association study of biochemical traits in Korcula Island, Croatia.
EBI GWAS Catalog
Genome-wide association study of obsessive-compulsive disorder.
EBI GWAS Catalog
GWAS of Longevity in CHARGE Consortium Confirms APOE and FOXO3 Candidacy.
EBI GWAS Catalog
Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.
EBI GWAS Catalog
Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.
EBI GWAS Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC74427

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables PDZ domain binding IEA
Inferred from Electronic Annotation
more info
  
enables SNARE binding IEA
Inferred from Electronic Annotation
more info
  
enables extracellularly glutamate-gated ion channel activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables identical protein binding IEA
Inferred from Electronic Annotation
more info
  
enables kainate selective glutamate receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables kainate selective glutamate receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential IEA
Inferred from Electronic Annotation
more info
  
enables scaffold protein binding IEA
Inferred from Electronic Annotation
more info
  
enables transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin conjugating enzyme binding IEA
Inferred from Electronic Annotation
more info
  
enables ubiquitin protein ligase binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in behavioral fear response IEA
Inferred from Electronic Annotation
more info
  
involved_in chemical synaptic transmission TAS
Traceable Author Statement
more info
 PubMed 
involved_in detection of cold stimulus involved in thermoception ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in excitatory postsynaptic potential IEA
Inferred from Electronic Annotation
more info
  
involved_in glutamate receptor signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in inhibitory postsynaptic potential IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular calcium ion homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in ionotropic glutamate receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in modulation of chemical synaptic transmission IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in modulation of chemical synaptic transmission IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in modulation of excitatory postsynaptic potential IEA
Inferred from Electronic Annotation
more info
  
involved_in monoatomic ion transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of synaptic transmission, glutamatergic IEA
Inferred from Electronic Annotation
more info
  
involved_in neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in neuronal action potential IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of synaptic transmission IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in presynaptic modulation of chemical synaptic transmission IEA
Inferred from Electronic Annotation
more info
  
involved_in receptor clustering IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of JNK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of long-term neuronal synaptic plasticity IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of presynaptic membrane potential IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of short-term neuronal synaptic plasticity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in synaptic transmission, glutamatergic IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in dendrite cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
located_in hippocampal mossy fiber to CA3 synapse IEA
Inferred from Electronic Annotation
more info
  
part_of kainate selective glutamate receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mossy fiber rosette IEA
Inferred from Electronic Annotation
more info
  
located_in perikaryon IEA
Inferred from Electronic Annotation
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
is_active_in postsynaptic density membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in presynaptic membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in terminal bouton IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
glutamate receptor ionotropic, kainate 2
Names
GluK2(alt_5'UTR)
bA487F5.1
excitatory amino acid receptor 4
gluR-6
glutamate receptor 6
glutamate receptor form A
glutamate receptor form B
glutamate receptor form C
glutamate receptor form D
glutamate receptor form E
putative NMDtranscript(cassette_171nt)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_009224.3 RefSeqGene

    Range
    5002..681377
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001166247.1 → NP_001159719.1  glutamate receptor ionotropic, kainate 2 isoform 3 precursor

    See identical proteins and their annotated locations for NP_001159719.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an additional exon in the 3' coding region, compared to transcript variant 1. The resulting isoform (3) is shorter and has a distinct C-terminus compared to isoform 1. RNA editing changes Ile567Val, Tyr571Cys and Gln621Arg.
    Source sequence(s)
    AJ252246, AP002530, BC037954
    Consensus CDS
    CCDS55045.1
    UniProtKB/TrEMBL
    A0A804HKP5
    Related
    ENSP00000358134.1, ENST00000369138.5
    Conserved Domains (2) summary
    cd06382
    Location:37 → 414
    PBP1_iGluR_Kainate; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate receptors
    cl21456
    Location:430 → 800
    Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily

  2. NM_021956.5 → NP_068775.1  glutamate receptor ionotropic, kainate 2 isoform 1 precursor

    See identical proteins and their annotated locations for NP_068775.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1). RNA editing changes Ile567Val, Tyr571Cys and Gln621Arg.
    Source sequence(s)
    AP002528, AP002529, AP002530
    Consensus CDS
    CCDS5048.1
    UniProtKB/Swiss-Prot
    A6NMY9, B5MCV0, D7RWZ3, D7RWZ4, D7RWZ5, D7RWZ6, D7RWZ7, Q13002, Q8WWS1, Q96KS6, Q96KS7, Q96KS8
    UniProtKB/TrEMBL
    A0A8D9PH75, A8K0H7
    Related
    ENSP00000358130.6, ENST00000369134.9
    Conserved Domains (2) summary
    cd06382
    Location:37 → 414
    PBP1_iGluR_Kainate; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate receptors
    cl21456
    Location:430 → 800
    Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily

  3. NM_175768.3 → NP_786944.1  glutamate receptor ionotropic, kainate 2 isoform 2 precursor

    See identical proteins and their annotated locations for NP_786944.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an additional exon in the 3' coding region, compared to transcript variant 1. The resulting isoform (2) is shorter and has a distinct C-terminus compared to isoform 1. RNA editing changes Ile567Val, Tyr571Cys and Gln621Arg.
    Source sequence(s)
    AJ301610, AK289542, AP002530, BC037954
    Consensus CDS
    CCDS5049.1
    UniProtKB/TrEMBL
    A0A804HKP5
    Related
    ENSP00000405596.1, ENST00000413795.5
    Conserved Domains (2) summary
    cd06382
    Location:37 → 414
    PBP1_iGluR_Kainate; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate receptors
    cl21456
    Location:430 → 800
    Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    101393708..102070083
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047418681.1 → XP_047274637.1  glutamate receptor ionotropic, kainate 2 isoform X1

    UniProtKB/Swiss-Prot
    A6NMY9, B5MCV0, D7RWZ3, D7RWZ4, D7RWZ5, D7RWZ6, D7RWZ7, Q13002, Q8WWS1, Q96KS6, Q96KS7, Q96KS8
    UniProtKB/TrEMBL
    A0A8D9PH75

  2. XM_047418682.1 → XP_047274638.1  glutamate receptor ionotropic, kainate 2 isoform X2

  3. XM_017010781.3 → XP_016866270.1  glutamate receptor ionotropic, kainate 2 isoform X4

    UniProtKB/TrEMBL
    A0A804HI04
    Related
    ENSP00000506840.1, ENST00000682222.1
    Conserved Domains (2) summary
    cd06382
    Location:37 → 414
    PBP1_iGluR_Kainate; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate receptors
    cl21456
    Location:430 → 702
    Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily

  4. XM_017010782.3 → XP_016866271.1  glutamate receptor ionotropic, kainate 2 isoform X5

    UniProtKB/TrEMBL
    A8K7F0
    Related
    ENSP00000508069.1, ENST00000682115.1

  5. XM_005266946.5 → XP_005267003.1  glutamate receptor ionotropic, kainate 2 isoform X3

    See identical proteins and their annotated locations for XP_005267003.1

    UniProtKB/TrEMBL
    B7Z8P6
    Conserved Domains (2) summary
    cd06382
    Location:1 → 365
    PBP1_iGluR_Kainate; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate receptors
    cl21456
    Location:381 → 751
    Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    102567441..103245122
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054355243.1 → XP_054211218.1  glutamate receptor ionotropic, kainate 2 isoform X1

    UniProtKB/Swiss-Prot
    A6NMY9, B5MCV0, D7RWZ3, D7RWZ4, D7RWZ5, D7RWZ6, D7RWZ7, Q13002, Q8WWS1, Q96KS6, Q96KS7, Q96KS8
    UniProtKB/TrEMBL
    A0A8D9PH75

  2. XM_054355244.1 → XP_054211219.1  glutamate receptor ionotropic, kainate 2 isoform X2

  3. XM_054355246.1 → XP_054211221.1  glutamate receptor ionotropic, kainate 2 isoform X4

  4. XM_054355247.1 → XP_054211222.1  glutamate receptor ionotropic, kainate 2 isoform X5

  5. XM_054355245.1 → XP_054211220.1  glutamate receptor ionotropic, kainate 2 isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13002.1 GenPept UniProtKB/Swiss-Prot:Q13002

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