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    GRIN2A glutamate ionotropic receptor NMDA type subunit 2A [ Homo sapiens (human) ]

    Gene ID: 2903, updated on 10-Dec-2024

    Summary

    Official Symbol
    GRIN2Aprovided by HGNC
    Official Full Name
    glutamate ionotropic receptor NMDA type subunit 2Aprovided by HGNC
    Primary source
    HGNC:HGNC:4585
    See related
    Ensembl:ENSG00000183454 MIM:138253; AllianceGenome:HGNC:4585
    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
    LKS; EPND; FESD; NR2A; GluN2A; NMDAR2A
    Summary
    This gene encodes a member of the glutamate-gated ion channel protein family. The encoded protein is an N-methyl-D-aspartate (NMDA) receptor subunit. NMDA receptors are both ligand-gated and voltage-dependent, and are involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. These receptors are permeable to calcium ions, and activation results in a calcium influx into post-synaptic cells, which results in the activation of several signaling cascades. Disruption of this gene is associated with focal epilepsy and speech disorder with or without cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
    Expression
    Biased expression in brain (RPKM 9.5), heart (RPKM 0.9) and 2 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See GRIN2A in Genome Data Viewer
    Location:
    16p13.2
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (9753404..10182908, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (9786917..10217640, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (9847261..10276765, complement)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC132205950 Neighboring gene RNA, 5S ribosomal pseudogene 403 Neighboring gene RNA, 5S ribosomal pseudogene 404 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr16:9764099-9764878 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:9767805-9768370 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:9768371-9768936 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:9770634-9771198 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr16:9771199-9771764 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:9773923-9774850 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:9774851-9775778 Neighboring gene uncharacterized LOC105371077 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10376 Neighboring gene NANOG hESC enhancer GRCh37_chr16:10050616-10051155 Neighboring gene uncharacterized LOC105371076 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:10132543-10133043 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7188 Neighboring gene Sharpr-MPRA regulatory region 8841 Neighboring gene inosine monophosphate dehydrogenase 1 pseudogene 11 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7189 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7190 Neighboring gene uncharacterized LOC107984900 Neighboring gene RNA, 7SL, cytoplasmic 493, pseudogene

    Genomic regions, transcripts, and products

    Expression

    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    BioGRID CRISPR Screen Phenotypes (9 hits/1268 screens)

    Associated conditions

    Description Tests
    Landau-Kleffner syndrome
    MedGen: C0282512 OMIM: 245570 GeneReviews: GRIN2A-Related Disorders
    Compare labs

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2024-09-25)

    ClinGen Genome Curation PagePubMed
    Triplosensitivity

    No evidence available (Last evaluated 2024-09-25)

    ClinGen Genome Curation Page

    EBI GWAS Catalog

    Description
    A genome-wide association study with DNA pooling identifies the variant rs11866328 in the GRIN2A gene that affects disease progression of chronic HBV infection.
    EBI GWAS Catalog
    A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.
    EBI GWAS Catalog
    Biological insights from 108 schizophrenia-associated genetic loci.
    EBI GWAS Catalog
    Common genetic variation and the control of HIV-1 in humans.
    EBI GWAS Catalog
    Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans.
    EBI GWAS Catalog
    Genome-wide association study identifies three susceptibility loci for laryngeal squamous cell carcinoma in the Chinese population.
    EBI GWAS Catalog
    Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
    EBI GWAS Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120-induced dephosphorylation of KV2.1 is dependent on NMDA receptor-mediated activation of protein phosphatase 2B or calcineurin PubMed
    env HIV-1 gp120 activates forward trafficking and surface clustering of NMDA receptors in membrane microdomains by a PKA-dependent phosphorylation of the NR1 C-terminal Ser897, followed by a PKC-dependent phosphorylation of Ser896 PubMed
    env HIV-1 gp120-induced synapse loss requires sequential activation of CXCR4, IL-1beta receptor, and NMDA receptor PubMed
    env HIV-1 gp120 activates NMDA receptor directly and phosphorylates JNK through a gp120-mediated apoptotic pathway in human neuroblastoma cells PubMed
    env HIV-1 clade B gp120 significantly downregulates NMDA receptor gene and protein expression and levels of glutamine compared to clade C gp120 PubMed
    env HIV-1 gp120-mediated human cell death involves the NMDA receptor complex; antagonists of the NMDA receptor reverse the gp120-mediated effects PubMed
    env HIV-1 gp120 causes an activation of phospholipase A2, resulting in the increased release of arachidonic acid, which may sensitize the NMDA receptor PubMed
    env HIV-1 gp120 binds to cells expressing epsilon1/zeta1 or epsilon2/zeta1 combined NMDA receptor subunits, but not to cells expressing a single epsilon1, epsilon2, or zeta1 NMDA receptor subunit PubMed
    Tat tat Ca(2+) influx through the NMDA receptor is necessary for HIV-1 Tat-induced synapse loss PubMed
    tat HIV-1 Tat increases in inhibitory synapse number in neurons are dependent on LRP binding and GluN2A-containing NMDAR activation but not PSD95 ubiquitination PubMed
    tat HIV-1 Tat upregulates the expression of NMDARs for the apoptosis of retinal pigmen epithelium (RPE) cells. Silencing of NMDARs by siRNA abolishes Tat-induced RPE apoptosis PubMed
    tat HIV-1 Tat-induced activation of spermine oxidase (SMO) activity involves NMDAR stimulation in human neuroblastoma PubMed
    tat HIV-1 Tat and methamphetamine inhibit the normal conjunction of signaling between D1 and NMDA receptors, resulting in neural dysfunction and death PubMed
    tat HIV-1 Tat interacts with NMDA receptors in primary neuronal-glial cultures and in hippocampal slice cultures PubMed
    tat HIV-1 Tat treatment induces the formation of complexes involving the low-density lipoprotein receptor-related protein (LRP), postsynaptic density protein-95 (PSD-95), and N-methyl-d-aspartic acid (NMDA) receptors at the neuron surface PubMed
    tat Tat treatment causes activation of neuronal nitric oxide synthase (nNOS) through association with NMDA receptors PubMed
    tat HIV-1 Tat treatment of human neurons results in tyrosine (Y) phosphorylation at position 1325 of the NMDAR subunit 2A (NR2A) in a src kinase-dependent manner PubMed
    tat HIV-1 Tat treatment of primary differentiated human neurons induces extensive apoptosis through increased amounts of NMDAR2A expression, but only low levels of apoptosis in primary immature human neurons result from low or minimal expression of NMDAR2A PubMed
    tat HIV-1 Tat-induced NMDA receptor activation is clade dependent. The Cys 30-Cys 31 motif in Tat is critical for the NMDA receptor activation PubMed
    tat HIV-1 Tat induces apoptosis of neurons and neurotoxicity through the activation of both NMDA and non-NMDA receptors PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    General gene information

    Gene Ontology Provided by GOA

    Items 1 - 25 of 45
    Process Evidence Code Pubs
    involved_in brain development PubMed 
    involved_in calcium ion transmembrane import into cytosol PubMed 
    involved_in calcium ion transmembrane import into cytosol PubMed 
    involved_in calcium ion transmembrane transport PubMed 
    involved_in calcium-mediated signaling  
    NOT involved_in cellular response to amyloid-beta PubMed 
    involved_in chemical synaptic transmission PubMed 
    involved_in directional locomotion  
    involved_in dopamine metabolic process  
    involved_in excitatory chemical synaptic transmission PubMed 
    involved_in excitatory postsynaptic potential  
    involved_in glutamate receptor signaling pathway PubMed 
    involved_in ionotropic glutamate receptor signaling pathway  
    involved_in ionotropic glutamate receptor signaling pathway  
    involved_in learning or memory PubMed 
    involved_in long-term synaptic potentiation  
    involved_in memory  
    involved_in monoatomic cation transmembrane transport PubMed 
    involved_in monoatomic cation transmembrane transport  
    involved_in monoatomic cation transmembrane transport  
    involved_in negative regulation of protein catabolic process  
    involved_in neurogenesis  
    involved_in positive regulation of apoptotic process  
    involved_in positive regulation of excitatory postsynaptic potential  
    involved_in positive regulation of excitatory postsynaptic potential  
    involved_in positive regulation of synaptic transmission, glutamatergic  
    involved_in positive regulation of synaptic transmission, glutamatergic  
    involved_in protein catabolic process  
    involved_in protein localization to postsynaptic membrane  
    involved_in regulation of monoatomic cation transmembrane transport  
    involved_in regulation of monoatomic cation transmembrane transport  
    involved_in regulation of neuronal synaptic plasticity PubMed 
    involved_in regulation of synaptic plasticity  
    involved_in regulation of synaptic plasticity PubMed 
    involved_in response to amphetamine  
    involved_in response to ethanol PubMed 
    involved_in response to wounding  
    involved_in response to xenobiotic stimulus  
    involved_in sensory perception of pain  
    involved_in serotonin metabolic process  
    involved_in sleep  
    involved_in sodium ion transmembrane transport PubMed 
    involved_in startle response  
    involved_in synaptic transmission, glutamatergic  
    involved_in visual learning  
    Items 1 - 25 of 45
    Items 1 - 20 of 22
    Component Evidence Code Pubs
    part_of NMDA selective glutamate receptor complex  
    part_of NMDA selective glutamate receptor complex PubMed 
    part_of NMDA selective glutamate receptor complex  
    part_of NMDA selective glutamate receptor complex  
    part_of NMDA selective glutamate receptor complex PubMed 
    located_in cell surface  
    located_in cytoplasmic vesicle membrane  
    located_in dendritic spine  
    located_in endoplasmic reticulum membrane  
    located_in glutamatergic synapse  
    is_active_in plasma membrane  
    located_in plasma membrane PubMed 
    located_in plasma membrane  
    located_in plasma membrane  
    located_in plasma membrane  
    located_in postsynaptic density  
    is_active_in postsynaptic density membrane  
    located_in postsynaptic membrane  
    located_in postsynaptic membrane PubMed 
    located_in presynaptic membrane  
    located_in synaptic membrane  
    located_in synaptic vesicle  
    Items 1 - 20 of 22

    General protein information

    Preferred Names
    glutamate receptor ionotropic, NMDA 2A
    Names
    N-methyl D-aspartate receptor subtype 2A
    N-methyl-D-aspartate receptor channel, subunit epsilon-1
    N-methyl-D-aspartate receptor subunit 2A
    glutamate ionotropic receptor NMDA 2A
    glutamate receptor, ionotropic, N-methyl D-aspartate 2A

    NCBI Reference Sequences (RefSeq)

    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.

    Genomic

    1. NG_011812.2 RefSeqGene

      Range
      5327..434347
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000833.5 → NP_000824.1  glutamate receptor ionotropic, NMDA 2A isoform 1 precursor

      See identical proteins and their annotated locations for NP_000824.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Transcript variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AC006531, AC007218, AC022168, U09002, U90277
      Consensus CDS
      CCDS10539.1
      UniProtKB/Swiss-Prot
      O00669, Q12879, Q17RZ6
      UniProtKB/TrEMBL
      Q547U9, Q59EW6
      Related
      ENSP00000379818.2, ENST00000396573.6
      Conserved Domains (5) summary
      cd06378
      Location:32 → 392
      PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
      COG0834
      Location:458 → 541
      HisJ; ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms]
      cd13718
      Location:403 → 802
      PBP2_iGluR_NMDA_Nr2; The ligand-binding domain of the NR2 subunit of ionotropic NMDA (N-methyl-D-aspartate) glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily
      pfam00060
      Location:556 → 828
      Lig_chan; Ligand-gated ion channel
      pfam10565
      Location:839 → 1464
      NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
    2. NM_001134407.3 → NP_001127879.1  glutamate receptor ionotropic, NMDA 2A isoform 1 precursor

      See identical proteins and their annotated locations for NP_001127879.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Transcript variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AB209695, AC006531, AC007218, AC022168, U09002
      Consensus CDS
      CCDS10539.1
      UniProtKB/Swiss-Prot
      O00669, Q12879, Q17RZ6
      UniProtKB/TrEMBL
      Q547U9, Q59EW6
      Related
      ENSP00000332549.3, ENST00000330684.4
      Conserved Domains (5) summary
      cd06378
      Location:32 → 392
      PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
      COG0834
      Location:458 → 541
      HisJ; ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms]
      cd13718
      Location:403 → 802
      PBP2_iGluR_NMDA_Nr2; The ligand-binding domain of the NR2 subunit of ionotropic NMDA (N-methyl-D-aspartate) glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily
      pfam00060
      Location:556 → 828
      Lig_chan; Ligand-gated ion channel
      pfam10565
      Location:839 → 1464
      NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
    3. NM_001134408.2 → NP_001127880.1  glutamate receptor ionotropic, NMDA 2A isoform 2 precursor

      See identical proteins and their annotated locations for NP_001127880.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has a shorter 5' UTR and is alternatively spliced at the 3' end, which results in a frameshift, compared to variant 1. The encoded isoform (2) has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC007218, BC143273, U90277
      Consensus CDS
      CCDS45407.1
      UniProtKB/TrEMBL
      A0A890YTL4, F5GZ52
      Related
      ENSP00000454998.1, ENST00000562109.5
      Conserved Domains (3) summary
      cd13718
      Location:403 → 802
      PBP2_iGluR_NMDA_Nr2; The ligand-binding domain of the NR2 subunit of ionotropic NMDA (N-methyl-D-aspartate) glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily
      cd06378
      Location:32 → 387
      PBP1_iGluR_NMDA_NR2; N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
      pfam10565
      Location:839 → 1258
      NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus

    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_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      9753404..10182908 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047433994.1 → XP_047289950.1  glutamate receptor ionotropic, NMDA 2A isoform X4

      UniProtKB/TrEMBL
      A0A890YTL4, F5GZ52
    2. XM_017023173.2 → XP_016878662.1  glutamate receptor ionotropic, NMDA 2A isoform X3

      UniProtKB/TrEMBL
      F5GZ52
      Related
      ENSP00000441572.3, ENST00000535259.6
    3. XM_047433993.1 → XP_047289949.1  glutamate receptor ionotropic, NMDA 2A isoform X2

      UniProtKB/Swiss-Prot
      O00669, Q12879, Q17RZ6
      UniProtKB/TrEMBL
      Q547U9, Q59EW6
    4. XM_017023172.2 → XP_016878661.1  glutamate receptor ionotropic, NMDA 2A isoform X1

      UniProtKB/TrEMBL
      Q59EW6
      Related
      ENSP00000502200.1, ENST00000674742.1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      9786917..10217640 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054380151.1 → XP_054236126.1  glutamate receptor ionotropic, NMDA 2A isoform X4

      UniProtKB/TrEMBL
      A0A890YTL4, F5GZ52
    2. XM_054380150.1 → XP_054236125.1  glutamate receptor ionotropic, NMDA 2A isoform X3

      UniProtKB/TrEMBL
      F5GZ52
    3. XM_054380149.1 → XP_054236124.1  glutamate receptor ionotropic, NMDA 2A isoform X2

      UniProtKB/Swiss-Prot
      O00669, Q12879, Q17RZ6
      UniProtKB/TrEMBL
      Q547U9, Q59EW6
    4. XM_054380148.1 → XP_054236123.1  glutamate receptor ionotropic, NMDA 2A isoform X1

      UniProtKB/TrEMBL
      Q59EW6
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