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

    Gene ID: 2900, updated on 3-Apr-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
    mouse all
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    Genomic context

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    Location:
    11q23.3
    Exon count:
    25
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (120511748..120988906)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (120535497..121012594)
    105.20220307 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
    • 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. Impact of GRIK4 gene polymorphisms on cognitive dysfunction in patients with major depression. Pu M, et al. Rev Neurol (Paris), 2020 Dec. PMID 32245654
    2. A kainate receptor GluK4 deletion, protective against bipolar disorder, is associated with enhanced cognitive performance across diagnoses in the TwinsUK cohort. Koromina M, et al. World J Biol Psychiatry, 2019 Jun. PMID 29243543
    3. No association of GRIK4 polymorphisms with schizophrenia in the Chinese Han population. Ren D, et al. Psychiatr Genet, 2017 Aug. PMID 28658089
    4. Common variants in GRIK4 and major depressive disorder: An association study in the Chinese Han population. Ren D, et al. Neurosci Lett, 2017 Jul 13. PMID 28583584
    5. The role of GRIK4 gene in treatment-resistant depression. Milanesi E, et al. Genet Res (Camb), 2015 Jul 3. PMID 26139080, Free PMC Article

    See all (40) 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 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_2023_10

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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