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GRIK4 glutamate ionotropic receptor kainate type subunit 4 [ Homo sapiens (human) ]

Gene ID: 2900, updated on 2-Nov-2024

Summary

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Official Symbol
GRIK4provided by HGNC
Official Full Name
glutamate ionotropic receptor kainate type subunit 4provided by HGNC
Primary source
HGNC:HGNC:4582
See related
Ensembl:ENSG00000149403 MIM:600282; AllianceGenome:HGNC:4582
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
KA1; EAA1; GRIK; GluK4; GluK4-2
Summary
This gene encodes a protein that belongs to the glutamate-gated ionic channel family. Glutamate functions as the major excitatory neurotransmitter in the central nervous system through activation of ligand-gated ion channels and G protein-coupled membrane receptors. The protein encoded by this gene forms functional heteromeric kainate-preferring ionic channels with the subunits encoded by related gene family members. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]
Expression
Biased expression in brain (RPKM 2.8), ovary (RPKM 0.9) and 4 other tissues See more
Orthologs
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Genomic context

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See GRIK4 in Genome Data Viewer
Location:
11q23.3
Exon count:
25
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (120511748..120988906)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (120535497..121012594)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (120382457..120859615)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3989 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3990 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3991 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:120224214-120224428 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 11:120249395 Neighboring gene Rho guanine nucleotide exchange factor 12 Neighboring gene TLC domain containing 5 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 11:120288060 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 11:120305787 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 11:120306759 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 11:120313899 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 11:120345004 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 11:120350393 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 11:120356317 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5637 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5638 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3993 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3992 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:120386966-120387568 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:120387569-120388170 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120402421-120402957 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120418648-120419393 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:120435257-120435837 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:120435838-120436417 Neighboring gene uncharacterized LOC107984400 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr11:120479691-120480414 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120480713-120481226 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5639 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120498105-120498605 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120504647-120505626 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr11:120515748-120516454 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr11:120516455-120517161 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120530966-120531466 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:120537690-120538200 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:120538201-120538710 Neighboring gene elongin C pseudogene 22 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120551815-120552316 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120566465-120566964 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5640 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120581457-120582198 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr11:120630117-120630617 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr11:120642173-120642737 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120646481-120647262 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120647263-120648044 Neighboring gene NANOG hESC enhancer GRCh37_chr11:120662921-120663458 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120667409-120667910 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120667911-120668410 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr11:120669439-120670113 Neighboring gene uncharacterized LOC105369532 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120704928-120705428 Neighboring gene uncharacterized LOC101929227 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:120744786-120745985 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120771587-120772086 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3995 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3996 Neighboring gene Sharpr-MPRA regulatory region 13304 Neighboring gene uncharacterized LOC101929208 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:120826209-120826709 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:120829234-120829455 Neighboring gene high mobility group box 1 pseudogene 42 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3997 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3998 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3999 Neighboring gene TBCEL-TECTA readthrough Neighboring gene HNF4 motif-containing MPRA enhancer 256 Neighboring gene tubulin folding cofactor E like Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr11:121000154-121001353 Neighboring gene tectorin alpha

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 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. Ontogeny of ionotropic glutamate receptor expression in human fetal brain. Ritter LM, et al. Brain Res Dev Brain Res, 2001 Apr 30. PMID 11334999
  2. A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. Pickard BS, et al. Proc Natl Acad Sci U S A, 2008 Sep 30. PMID 18824690, Free PMC Article
  3. Cytogenetic and genetic evidence supports a role for the kainate-type glutamate receptor gene, GRIK4, in schizophrenia and bipolar disorder. Pickard BS, et al. Mol Psychiatry, 2006 Sep. PMID 16819533
  4. A GRIK4 variant conferring protection against bipolar disorder modulates hippocampal function. Whalley HC, et al. Mol Psychiatry, 2009 May. PMID 19384319
  5. Glutamate signaling through the kainate receptor enhances human immunoglobulin production. Sturgill JL, et al. J Neuroimmunol, 2011 Apr. PMID 21215464, Free PMC Article

See all (41) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Impact of GRIK4 gene polymorphisms on cognitive dysfunction in patients with major depression.
    Title: Impact of GRIK4 gene polymorphisms on cognitive dysfunction in patients with major depression.
  2. In addition, while GRIK4 was not associated with sertraline tolerability and response, both HTR2A and SLC6A4 could influence tolerability and accelerate treatment response in pediatric patients.
    Title: Pharmacogenetics of Sertraline Tolerability and Response in Pediatric Anxiety and Depressive Disorders.
  3. GluK4 deletion carriers who had a mental health problem (predominately depression) showed better performance in visuo-spatial ability and mental processing speed compared to individuals with mental health problems homozygous for the insertion.
    Title: A kainate receptor GluK4 deletion, protective against bipolar disorder, is associated with enhanced cognitive performance across diagnoses in the TwinsUK cohort.
  4. the GRIK4 polymorphisms genotypes were distributed as follows: rs79526501: CC696: 16, CG302: 274, GG31: 35; rs11218016: CC455: 483, CT473: 436, TT101: 108; and rs6589847: AA32: 29, AG307: 314, GG690: 686. However, there was no significant difference in allelic or genotypic frequency distributions between patients and controls. We did not find any significant association between GRIK4 polymorphisms and schizophrenia.
    Title: No association of GRIK4 polymorphisms with schizophrenia in the Chinese Han population.
  5. Results firstly indicated that rs56275759 of GRIK4 gene might be associated with major depressive disorder in Chinese Han population.
    Title: Common variants in GRIK4 and major depressive disorder: An association study in the Chinese Han population.
  6. This study showed the lower GluK4 mRNA levels in pregnant women.
    Title: AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women.
  7. Data suggest the involvement of glutamate receptor, ionotropic, kainate 4 protein (GRIK4) in treatment-resistant depression (TRD) and in the risk of developing psychotic symptoms during depressive episodes.
    Title: The role of GRIK4 gene in treatment-resistant depression.
  8. Subjects possessing the C allele or CC genotype of the GRIK4 polymorphism rs1954787 are more likely to respond to antidepressant treatment.
    Title: GRIK4 polymorphism and its association with antidepressant response in depressed patients: a meta-analysis.
  9. The deletion allele affords protection against bipolar disorder through increased KA1 protein abundance in neuronal cells.
    Title: GRIK4/KA1 protein expression in human brain and correlation with bipolar disorder risk variant status.
  10. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Submit: New GeneRIF Correction See all GeneRIFs (20)

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

EBI GWAS Catalog

Description
Common genetic variation and performance on standardized cognitive tests.
EBI GWAS Catalog
Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: genome-wide association study of both common and rare variants.
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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables kainate selective glutamate receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential IDA
Inferred from Direct Assay
more info
 PubMed 
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential NAS
Non-traceable Author Statement
more info
 PubMed 
enables transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in chemical synaptic transmission TAS
Traceable Author Statement
more info
 PubMed 
involved_in glutamate receptor signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
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 monoatomic ion transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of postsynaptic membrane potential IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of presynaptic membrane potential IEA
Inferred from Electronic Annotation
more info
  
involved_in synaptic transmission, glutamatergic IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in cell projection 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
  
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
  

General protein information

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Preferred Names
glutamate receptor ionotropic, kainate 4
Names
GluK4(alt_5'UTR)
excitatory amino acid receptor 1
glutamate receptor KA1
glutamate receptor, ionotropic, kainate 4
putative NMDtranscript(altAcc_e11)

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_042194.1 RefSeqGene

    Range
    5001..482060
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1012

mRNA and Protein(s)

  1. NM_001282470.3 → NP_001269399.1  glutamate receptor ionotropic, kainate 4 isoform 1 precursor

    See identical proteins and their annotated locations for NP_001269399.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. Both this variant and variant 2 encode the same isoform (1).
    Source sequence(s)
    AK292726, AK314284, AP001929, AP002348, AW016926
    Consensus CDS
    CCDS8433.1
    UniProtKB/Swiss-Prot
    A8K9L1, Q16099
    UniProtKB/TrEMBL
    A0A8D9PH79, B2RAP6
    Related
    ENSP00000404063.2, ENST00000438375.2
    Conserved Domains (2) summary
    cd13724
    Location:415 → 785
    PBP2_iGluR_kainate_KA1; The ligand-binding domain of the kainate subtype KA1 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily
    cd06394
    Location:24 → 402
    PBP1_iGluR_Kainate_KA1_2; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the KA1 and KA2 subunits of Kainate receptor

  2. NM_001282473.3 → NP_001269402.1  glutamate receptor ionotropic, kainate 4 isoform 2 precursor

    See identical proteins and their annotated locations for NP_001269402.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has an additional exon in the 5' UTR but lacks several 3' terminal exons, compared to variant 1. Its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR. The resulting isoform (2) is shorter and has a distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AK314284, AP001929, AP002348, BC146652
    UniProtKB/TrEMBL
    A6H8K8
    Related
    ENST00000533291.5
    Conserved Domains (4) summary
    cd06394
    Location:26 → 400
    PBP1_iGluR_Kainate_KA1_2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the KA1 and KA2 subunits of Kainate receptor
    pfam00060
    Location:547 → 756
    Lig_chan; Ligand-gated ion channel
    pfam01094
    Location:43 → 382
    ANF_receptor; Receptor family ligand binding region
    cl21456
    Location:415 → 763
    Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily

  3. NM_014619.5 → NP_055434.2  glutamate receptor ionotropic, kainate 4 isoform 1 precursor

    See identical proteins and their annotated locations for NP_055434.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and encodes the same isoform (1), compared to variant 1.
    Source sequence(s)
    AK292726, AP001929, AW016926, DA246271, DB306924
    Consensus CDS
    CCDS8433.1
    UniProtKB/Swiss-Prot
    A8K9L1, Q16099
    UniProtKB/TrEMBL
    A0A8D9PH79, B2RAP6
    Related
    ENSP00000435648.2, ENST00000527524.8
    Conserved Domains (2) summary
    cd13724
    Location:415 → 785
    PBP2_iGluR_kainate_KA1; The ligand-binding domain of the kainate subtype KA1 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily
    cd06394
    Location:24 → 402
    PBP1_iGluR_Kainate_KA1_2; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the KA1 and KA2 subunits of Kainate receptor

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    120511748..120988906
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017017621.3 → XP_016873110.1  glutamate receptor ionotropic, kainate 4 isoform X2

    UniProtKB/TrEMBL
    B2RAP6

  2. XM_017017622.3 → XP_016873111.1  glutamate receptor ionotropic, kainate 4 isoform X3

    UniProtKB/TrEMBL
    B2RAP6

  3. XM_011542784.3 → XP_011541086.1  glutamate receptor ionotropic, kainate 4 isoform X1

    UniProtKB/TrEMBL
    A0A8D9UJ88, B2RAP6
    Conserved Domains (2) summary
    cd13724
    Location:361 → 731
    PBP2_iGluR_kainate_KA1; The ligand-binding domain of the kainate subtype KA1 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily
    cl10011
    Location:24 → 348
    Periplasmic_Binding_Protein_type1; Type 1 periplasmic binding fold superfamily

  4. XM_047426840.1 → XP_047282796.1  glutamate receptor ionotropic, kainate 4 isoform X4

  5. XM_011542786.3 → XP_011541088.1  glutamate receptor ionotropic, kainate 4 isoform X5

    Conserved Domains (3) summary
    cd13724
    Location:173 → 543
    PBP2_iGluR_kainate_KA1; The ligand-binding domain of the kainate subtype KA1 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily
    pfam00060
    Location:305 → 574
    Lig_chan; Ligand-gated ion channel
    cl10011
    Location:7 → 158
    Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily

  6. XM_011542787.3 → XP_011541089.1  glutamate receptor ionotropic, kainate 4 isoform X6

    See identical proteins and their annotated locations for XP_011541089.1

    Conserved Domains (3) summary
    cd13724
    Location:161 → 531
    PBP2_iGluR_kainate_KA1; The ligand-binding domain of the kainate subtype KA1 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily
    pfam00060
    Location:293 → 562
    Lig_chan; Ligand-gated ion channel
    cl10011
    Location:1 → 146
    Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    120535497..121012594
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054368569.1 → XP_054224544.1  glutamate receptor ionotropic, kainate 4 isoform X2

  2. XM_054368570.1 → XP_054224545.1  glutamate receptor ionotropic, kainate 4 isoform X3

  3. XM_054368568.1 → XP_054224543.1  glutamate receptor ionotropic, kainate 4 isoform X1

    UniProtKB/TrEMBL
    A0A8D9UJ88

  4. XM_054368571.1 → XP_054224546.1  glutamate receptor ionotropic, kainate 4 isoform X4

  5. XM_054368572.1 → XP_054224547.1  glutamate receptor ionotropic, kainate 4 isoform X5

  6. XM_054368573.1 → XP_054224548.1  glutamate receptor ionotropic, kainate 4 isoform X6

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q16099.2 GenPept UniProtKB/Swiss-Prot:Q16099

Gene LinkOut

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