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

Summary

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: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 11q22.3

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (105609616..105982090)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (105613870..105986693)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (105480800..105852817)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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

Go to the top of the page Help

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	Compare labs

EBI GWAS Catalog

Description
Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

SHGC-106294 (e-PCR)
- UniSTS:169729

SHGC-79000 (e-PCR)
- UniSTS:101383

D11S1325 (e-PCR), detects polymorphism
- UniSTS:27658

WI-20616 (e-PCR)
- UniSTS:1295

RH121888 (e-PCR)
- UniSTS:137743

G30957 (e-PCR)
- UniSTS:2329

SHGC-142178 (e-PCR)
- UniSTS:171302

G17587 (e-PCR)
- UniSTS:5680

SHGC-173555 (e-PCR)
- UniSTS:185392

SHGC-83229 (e-PCR)
- UniSTS:95800

D11S4039 (e-PCR)
- UniSTS:75327

D11S2000 (e-PCR)
- UniSTS:15936

RH11819 (e-PCR)
- UniSTS:32577

SHGC-31826 (e-PCR)
- UniSTS:32578

SGC30893 (e-PCR)
- UniSTS:62021

D11S1816 (e-PCR)
- UniSTS:148829

D11S1325 (e-PCR), detects polymorphism
- UniSTS:79199

D11S3070 (e-PCR)
- UniSTS:152167

G27433 (e-PCR)
- UniSTS:10603

D11S3084 (e-PCR)
- UniSTS:152180

D11S2275E (e-PCR)
- UniSTS:151413

RH27781 (e-PCR)
- UniSTS:89718

RH91882 (e-PCR)
- UniSTS:92534

G17613 (e-PCR)
- UniSTS:6786

G59265 (e-PCR)
- UniSTS:136580

G65580 (e-PCR)
- UniSTS:225424

RH99092 (e-PCR)
- UniSTS:91798

RH12402 (e-PCR)
- UniSTS:4538

SHGC-36942 (e-PCR)
- UniSTS:2759

SHGC-152865 (e-PCR)
- UniSTS:177615

D11S4621 (e-PCR)
- UniSTS:57314

WI-21644 (e-PCR)
- UniSTS:70143

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 protein binding	IPI Inferred from Physical Interaction 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
located_in dendrite	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 more info	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	ISS Inferred from Sequence or Structural Similarity 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

Go to the top of the page Help

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)

Go to the top of the page Help

NEW Try the new Transcript table

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)

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
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
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
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

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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

105609616..105982090

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
XM_047426831.1 → XP_047282787.1 glutamate receptor 4 isoform X2
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
XM_017017610.3 → XP_016873099.1 glutamate receptor 4 isoform X4

UniProtKB/TrEMBL

Q59GL7
XM_017017609.2 → XP_016873098.1 glutamate receptor 4 isoform X3

UniProtKB/TrEMBL

A0A994J6J2, Q59GL7

Related

ENSP00000515457.2, ENST00000703743.2
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
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
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