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GRIA4 glutamate ionotropic receptor AMPA type subunit 4 [ Homo sapiens (human) ]

Gene ID: 2893, updated on 3-Apr-2024

Summary

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Official Symbol
GRIA4provided by HGNC
Official Full Name
glutamate ionotropic receptor AMPA type subunit 4provided by HGNC
Primary source
HGNC:HGNC:4574
See related
Ensembl:ENSG00000152578 MIM:138246; AllianceGenome:HGNC:4574
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
GLUR4; GLURD; GluA4; GLUR4C; NEDSGA; GluA4-ATD
Summary
Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes composed of multiple subunits, arranged to form ligand-gated ion channels. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The subunit encoded by this gene belongs to a family of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive glutamate receptors, and is subject to RNA editing (AGA->GGA; R->G). Alternative splicing of this gene results in transcript variants encoding different isoforms, which may vary in their signal transduction properties. Some haplotypes of this gene show a positive association with schizophrenia. [provided by RefSeq, Jul 2008]
Expression
Biased expression in brain (RPKM 8.8), adrenal (RPKM 0.9) and 1 other tissue See more
Orthologs
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Genomic context

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See GRIA4 in Genome Data Viewer
Location:
11q22.3
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (105609616..105982090)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (105613870..105986693)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (105480800..105852817)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369468 Neighboring gene uncharacterized LOC105369469 Neighboring gene olfactory receptor family 2 subfamily AL member 1 pseudogene Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr11:105167667-105168866 Neighboring gene MPRA-validated peak1445 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5461 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5462 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:105623830-105625029 Neighboring gene heat shock protein family D (Hsp60) member 1 pseudogene 13 Neighboring gene NANOG hESC enhancer GRCh37_chr11:105670634-105671137 Neighboring gene RNA, U4 small nuclear 55, pseudogene Neighboring gene uncharacterized LOC124902743 Neighboring gene RNA, U6 small nuclear 277, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5463 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3868 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5464 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5465 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5466 Neighboring gene Myb/SANT DNA binding domain containing 4 with coiled-coils Neighboring gene kelch repeat and BTB domain containing 3

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. Colorectal cancer promoter methylation alteration affects the expression of glutamate ionotropic receptor AMPA type subunit 4 alternative isoforms potentially relevant in colon tissue. Vega-Benedetti AF, et al. Hum Cell, 2022 Jan. PMID 34719006, Free PMC Article
  2. Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression. Zhou H, et al. Transl Psychiatry, 2018 Oct 4. PMID 30287806, Free PMC Article
  3. De Novo Variants in GRIA4 Lead to Intellectual Disability with or without Seizures and Gait Abnormalities. Martin S, et al. Am J Hum Genet, 2017 Dec 7. PMID 29220673, Free PMC Article
  4. Kinetic mechanism of channel opening of the GluRDflip AMPA receptor. Li G, et al. Biochemistry, 2005 Apr 19. PMID 15823042
  5. No genetic association between polymorphisms in the AMPA receptor subunit GluR4 gene (GRIA4) and schizophrenia in the Chinese population. Guo S, et al. Neurosci Lett, 2004 Oct 14. PMID 15450689

See all (69) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Association of SLC12A1 and GLUR4 Ion Transporters with Neoadjuvant Chemoresistance in Luminal Locally Advanced Breast Cancer.
    Title: Association of SLC12A1 and GLUR4 Ion Transporters with Neoadjuvant Chemoresistance in Luminal Locally Advanced Breast Cancer.
  2. Colorectal cancer promoter methylation alteration affects the expression of glutamate ionotropic receptor AMPA type subunit 4 alternative isoforms potentially relevant in colon tissue.
    Title: Colorectal cancer promoter methylation alteration affects the expression of glutamate ionotropic receptor AMPA type subunit 4 alternative isoforms potentially relevant in colon tissue.
  3. Study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression.
    Title: Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression.
  4. The authors suggest that pathogenic de novo variants in GRIA4 lead to intellectual disability with or without seizures, gait abnormalities, problems of social behavior, and other variable features.
    Title: De Novo Variants in GRIA4 Lead to Intellectual Disability with or without Seizures and Gait Abnormalities.
  5. Study shows that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluA4 is expressed on oligodendrocytes, myelin and on axons in humans.
    Title: Ionotropic glutamate receptor expression in human white matter.
  6. A transient positive feedback mechanism between AMPAR and stargazin has implications for information processing in the brain, because it should allow activity-dependent facilitation of excitatory synaptic transmission through a postsynaptic mechanism.
    Title: Superactivation of AMPA receptors by auxiliary proteins.
  7. This study demonstrated that the GRIA4 protein was altered in auditory cortex patient with schizophreia.
    Title: Altered glutamate protein co-expression network topology linked to spine loss in the auditory cortex of schizophrenia.
  8. Interaction with the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR4.
    Title: Neuronal pentraxin 2 supports clear cell renal cell carcinoma by activating the AMPA-selective glutamate receptor-4.
  9. the levels were comparable for complexes containing GluR2, GluR3 and GluR4 as well as 5-HT1A. Moreover, the levels of complexes containing muscarinic AChR M1, NR1 and GluR1 were significantly increased in male patients with AD.
    Title: Changes of several brain receptor complexes in the cerebral cortex of patients with Alzheimer disease: probable new potential pharmaceutical targets.
  10. Statistical analysis showed no association between migraine and the GRIA2 and GRIA4 polymorphisms investigated.
    Title: Genetic analysis of GRIA2 and GRIA4 genes in migraine.
Submit: New GeneRIF Correction See all GeneRIFs (29)

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
Neurodevelopmental disorder with or without seizures and gait abnormalities
MedGen: C4693391 OMIM: 617864 GeneReviews: Not available
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EBI GWAS Catalog

Description
Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects.
EBI GWAS Catalog
Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia.
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 AMPA glutamate receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables AMPA glutamate receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables amyloid-beta binding NAS
Non-traceable Author Statement
more info
 PubMed 
enables glutamate-gated receptor activity ISS
Inferred from Sequence or Structural Similarity
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 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 negative regulation of smooth muscle cell apoptotic process IGI
Inferred from Genetic Interaction
more info
 PubMed 
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
part_of AMPA glutamate receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of AMPA glutamate receptor complex ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in dendritic spine IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in dendritic spine ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in endocytic vesicle membrane TAS
Traceable Author Statement
more info
  
located_in extracellular vesicle HDA PubMed 
located_in neuronal cell body ISS
Inferred from Sequence or Structural Similarity
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
  

General protein information

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Preferred Names
glutamate receptor 4
Names
AMPA-selective glutamate receptor 4
gluR-4
gluR-D
glutamate receptor, ionotrophic, AMPA 4
glutamate receptor, ionotropic, AMPA 4

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.

mRNA and Protein(s)

  1. NM_000829.4 → NP_000820.4  glutamate receptor 4 isoform 1 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1). RNA editing (AGA->GGA) changes Arg765Gly.
    Source sequence(s)
    AP000641, AP000673, AP000813, AP001561
    Consensus CDS
    CCDS8333.1
    UniProtKB/Swiss-Prot
    P48058, Q86XE8
    UniProtKB/TrEMBL
    Q1WWK6
    Related
    ENSP00000282499.5, ENST00000282499.10
    Conserved Domains (2) summary
    cd06388
    Location:28 → 398
    PBP1_iGluR_AMPA_GluR4; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the GluR4 subunit of the AMPA receptor
    cd13727
    Location:414 → 795
    PBP2_iGluR_AMPA_GluR4; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR4 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

  2. NM_001077243.3 → NP_001070711.3  glutamate receptor 4 isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an alternate in-frame coding exon, and uses a downstream donor splice site at the penultimate exon, compared to transcript variant 1. This results in a shorter isoform (2) with a different C-terminus compared to isoform 1. RNA editing (AGA->GGA) changes Arg765Gly.
    Source sequence(s)
    AP000641, AP000673, AP000813, AP001561
    Consensus CDS
    CCDS41706.1
    UniProtKB/TrEMBL
    G3V164, Q1WWK6
    Related
    ENSP00000432180.1, ENST00000525187.6
    Conserved Domains (2) summary
    cd13727
    Location:414 → 795
    PBP2_iGluR_AMPA_GluR4; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR4 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily
    cd06388
    Location:28 → 400
    PBP1_iGluR_AMPA_GluR4; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the GluR4 subunit of the AMPA receptor

  3. NM_001077244.2 → NP_001070712.1  glutamate receptor 4 isoform 3 precursor

    See identical proteins and their annotated locations for NP_001070712.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) is missing several coding exons at the 3' end, and contains a novel 3' terminal exon compared to transcript variant 1. This results in a shorter isoform (3) with a different C-terminus compared to isoform 1. Variants 3 and 4 encode the same isoform.
    Source sequence(s)
    AP000673, BC045546, DB473702, DB548729
    Consensus CDS
    CCDS41707.1
    UniProtKB/TrEMBL
    A0A8D9PH77, A6QL61
    Related
    ENSP00000376833.2, ENST00000393125.6
    Conserved Domains (1) summary
    cd06388
    Location:28 → 400
    PBP1_iGluR_AMPA_GluR4; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the GluR4 subunit of the AMPA receptor

  4. NM_001112812.2 → NP_001106283.1  glutamate receptor 4 isoform 3 precursor

    See identical proteins and their annotated locations for NP_001106283.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) is missing a 5' non-coding exon and several coding exons at the 3' end, and contains a novel 3' terminal exon compared to transcript variant 1. This results in a shorter isoform (3) with a different C-terminus compared to isoform 1. Variants 3 and 4 have different 5' UTR, but encode the same isoform.
    Source sequence(s)
    AP000673, BC015199, BC045546, DA391203, DB548729
    Consensus CDS
    CCDS41707.1
    UniProtKB/TrEMBL
    A0A8D9PH77, A6QL61
    Related
    ENSP00000415551.2, ENST00000428631.6
    Conserved Domains (1) summary
    cd06388
    Location:28 → 400
    PBP1_iGluR_AMPA_GluR4; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the GluR4 subunit of the AMPA receptor

RNA

  1. NR_046356.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR and contains an alternate exon compared to variant 1. The alternate exon has an in-frame stop codon that renders this transcript a candidate for nonsense-mediated mRNA decay (NMD). Therefore, this transcript is not likely to be protein-coding.
    Source sequence(s)
    AP000641, AP000673, AP000813, AP001561

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
    105609616..105982090
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006718823.3 → XP_006718886.1  glutamate receptor 4 isoform X1

    See identical proteins and their annotated locations for XP_006718886.1

    UniProtKB/Swiss-Prot
    P48058, Q86XE8
    UniProtKB/TrEMBL
    Q1WWK6
    Conserved Domains (2) summary
    cd06388
    Location:28 → 398
    PBP1_iGluR_AMPA_GluR4; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the GluR4 subunit of the AMPA receptor
    cd13727
    Location:414 → 795
    PBP2_iGluR_AMPA_GluR4; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR4 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

  2. XM_024448454.2 → XP_024304222.1  glutamate receptor 4 isoform X6

    UniProtKB/TrEMBL
    A0A8D9PH77, A6QL61
    Conserved Domains (1) summary
    cd06388
    Location:28 → 400
    PBP1_iGluR_AMPA_GluR4; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the GluR4 subunit of the AMPA receptor

  3. XM_047426831.1 → XP_047282787.1  glutamate receptor 4 isoform X2

  4. XM_005271518.4 → XP_005271575.1  glutamate receptor 4 isoform X2

    See identical proteins and their annotated locations for XP_005271575.1

    UniProtKB/TrEMBL
    Q1WWK6
    Conserved Domains (4) summary
    cd06388
    Location:28 → 398
    PBP1_iGluR_AMPA_GluR4; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the GluR4 subunit of the AMPA receptor
    cd13727
    Location:414 → 795
    PBP2_iGluR_AMPA_GluR4; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR4 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily
    pfam00060
    Location:546 → 825
    Lig_chan; Ligand-gated ion channel
    pfam01094
    Location:39 → 380
    ANF_receptor; Receptor family ligand binding region

  5. XM_017017610.3 → XP_016873099.1  glutamate receptor 4 isoform X4

    UniProtKB/TrEMBL
    Q59GL7

  6. XM_017017609.2 → XP_016873098.1  glutamate receptor 4 isoform X3

    UniProtKB/TrEMBL
    A0A994J6J2, Q59GL7
    Related
    ENSP00000515457.2, ENST00000703743.2

  7. XM_024448455.2 → XP_024304223.1  glutamate receptor 4 isoform X7

    UniProtKB/TrEMBL
    A6QL61
    Conserved Domains (1) summary
    cd06388
    Location:28 → 398
    PBP1_iGluR_AMPA_GluR4; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the GluR4 subunit of the AMPA receptor

  8. XM_011542777.4 → XP_011541079.1  glutamate receptor 4 isoform X5

    See identical proteins and their annotated locations for XP_011541079.1

    Conserved Domains (4) summary
    cd13727
    Location:244 → 625
    PBP2_iGluR_AMPA_GluR4; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR4 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily
    pfam00060
    Location:376 → 655
    Lig_chan; Ligand-gated ion channel
    pfam01094
    Location:1 → 210
    ANF_receptor; Receptor family ligand binding region
    cl10011
    Location:1 → 228
    Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily

  9. XM_017017611.3 → XP_016873100.1  glutamate receptor 4 isoform X5

    Conserved Domains (4) summary
    cd13727
    Location:244 → 625
    PBP2_iGluR_AMPA_GluR4; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR4 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily
    pfam00060
    Location:376 → 655
    Lig_chan; Ligand-gated ion channel
    pfam01094
    Location:1 → 210
    ANF_receptor; Receptor family ligand binding region
    cl10011
    Location:1 → 228
    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
    105613870..105986693
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054368546.1 → XP_054224521.1  glutamate receptor 4 isoform X1

    UniProtKB/Swiss-Prot
    P48058, Q86XE8

  2. XM_054368553.1 → XP_054224528.1  glutamate receptor 4 isoform X6

    UniProtKB/TrEMBL
    A0A8D9PH77

  3. XM_054368548.1 → XP_054224523.1  glutamate receptor 4 isoform X2

  4. XM_054368547.1 → XP_054224522.1  glutamate receptor 4 isoform X2

  5. XM_054368549.1 → XP_054224524.1  glutamate receptor 4 isoform X3

    UniProtKB/TrEMBL
    A0A994J6J2

  6. XM_054368550.1 → XP_054224525.1  glutamate receptor 4 isoform X4

  7. XM_054368554.1 → XP_054224529.1  glutamate receptor 4 isoform X7

  8. XM_054368551.1 → XP_054224526.1  glutamate receptor 4 isoform X5

  9. XM_054368552.1 → XP_054224527.1  glutamate receptor 4 isoform X5

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P48058.2 GenPept UniProtKB/Swiss-Prot:P48058

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