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    GRID2 glutamate ionotropic receptor delta type subunit 2 [ Homo sapiens (human) ]

    Gene ID: 2895, updated on 28-Oct-2024

    Summary

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    Official Symbol
    GRID2provided by HGNC
    Official Full Name
    glutamate ionotropic receptor delta type subunit 2provided by HGNC
    Primary source
    HGNC:HGNC:4576
    See related
    Ensembl:ENSG00000152208 MIM:602368; AllianceGenome:HGNC:4576
    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
    GluD2; SCAR18
    Summary
    The protein encoded by this gene is a member of the family of ionotropic glutamate receptors which are the predominant excitatory neurotransmitter receptors in the mammalian brain. The encoded protein is a multi-pass membrane protein that is expressed selectively in cerebellar Purkinje cells. A point mutation in the mouse ortholog, associated with the phenotype named 'lurcher', in the heterozygous state leads to ataxia resulting from selective, cell-autonomous apoptosis of cerebellar Purkinje cells during postnatal development. Mice homozygous for this mutation die shortly after birth from massive loss of mid- and hindbrain neurons during late embryogenesis. This protein also plays a role in synapse organization between parallel fibers and Purkinje cells. Alternate splicing results in multiple transcript variants encoding distinct isoforms. Mutations in this gene cause cerebellar ataxia in humans. [provided by RefSeq, Apr 2014]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
    mouse all
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    Genomic context

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    See GRID2 in Genome Data Viewer
    Location:
    4q22.1-q22.2
    Exon count:
    27
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (92303966..93810456)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (95630513..97125831)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (93225117..94695717)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:93104511-93105710 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:93192087-93192994 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:93193903-93194810 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr4:93194811-93195716 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:93197533-93198440 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:93198441-93199346 Neighboring gene PMPCA pseudogene 1 Neighboring gene Sharpr-MPRA regulatory region 6143 Neighboring gene lncRNA p53 regulated and ESC associated 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:93353264-93354196 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr4:93354197-93355129 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:93358086-93358597 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:93359794-93360688 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:93360689-93361582 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:93361583-93362476 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:93366052-93366944 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:93365158-93366051 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:93440900-93441601 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:93441602-93442302 Neighboring gene MT-ND1 pseudogene 19 Neighboring gene RACK1 pseudogene 3 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:94068335-94068896 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21726 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:94287122-94287935 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:94329999-94330773 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr4:94506413-94507612 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:94564478-94565145 Neighboring gene Sharpr-MPRA regulatory region 1337 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21727 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21728 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15573 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:94748021-94748726 Neighboring gene RNA, 5S ribosomal pseudogene 164 Neighboring gene atonal bHLH transcription factor 1

    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. Neurodevelopmental Syndrome with Intellectual Disability, Speech Impairment, and Quadrupedia Is Associated with Glutamate Receptor Delta 2 Gene Defect. Grigorenko AP, et al. Cells, 2022 Jan 25. PMID 35159210, Free PMC Article
    2. A homozygous deletion in GRID2 causes a human phenotype with cerebellar ataxia and atrophy. Utine GE, et al. J Child Neurol, 2013 Jul. PMID 23611888
    3. Autosomal recessive spinocerebellar ataxia 18 caused by homozygous exon 14 duplication in GRID2 and review of the literature. Ceylan AC, et al. Acta Neurol Belg, 2021 Dec. PMID 32170608
    4. Association of Gene Variations in Ionotropic Glutamate Receptor and Attention-Deficit/Hyperactivity Disorder in the Chinese Population: A Two-Stage Case-Control Study. Zhang Q, et al. J Atten Disord, 2021 Aug. PMID 32065002
    5. Homozygous GRID2 missense mutation predicts a shift in the D-serine binding domain of GluD2 in a case with generalized brain atrophy and unusual clinical features. Ali Z, et al. BMC Med Genet, 2017 Dec 6. PMID 29207948, Free PMC Article

    See all (40) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Clinical features, functional consequences, and rescue pharmacology of missense GRID1 and GRID2 human variants.
      Title: Clinical features, functional consequences, and rescue pharmacology of missense GRID1 and GRID2 human variants.
    2. Neurodevelopmental Syndrome with Intellectual Disability, Speech Impairment, and Quadrupedia Is Associated with Glutamate Receptor Delta 2 Gene Defect.
      Title: Neurodevelopmental Syndrome with Intellectual Disability, Speech Impairment, and Quadrupedia Is Associated with Glutamate Receptor Delta 2 Gene Defect.
    3. Autosomal recessive spinocerebellar ataxia 18 caused by homozygous exon 14 duplication in GRID2 and review of the literature.
      Title: Autosomal recessive spinocerebellar ataxia 18 caused by homozygous exon 14 duplication in GRID2 and review of the literature.
    4. Association of Gene Variations in Ionotropic Glutamate Receptor and Attention-Deficit/Hyperactivity Disorder in the Chinese Population: A Two-Stage Case-Control Study.
      Title: Association of Gene Variations in Ionotropic Glutamate Receptor and Attention-Deficit/Hyperactivity Disorder in the Chinese Population: A Two-Stage Case-Control Study.
    5. Report on a consanguineous family with autosomal recessive childhood onset of cerebellar ataxia and delayed psychomotor development. Using whole exome sequencing we identified a novel homozygous missense variant [c.2128C > T, p.(Arg710Trp)] in GRID2 that segregates with the disease. The missense variant is located in a conserved region encoding the extracellular serine-binding domain of the GluD2 protein.
      Title: Homozygous GRID2 missense mutation predicts a shift in the D-serine binding domain of GluD2 in a case with generalized brain atrophy and unusual clinical features.
    6. GRID2 gene can be a suppressor in TNF-induced neurodegeneration which may help to understand the main factors leading to autism.
      Title: Potential of GRID2 receptor gene for preventing TNF-induced neurodegeneration in autism.
    7. Glutamate system genes including have been associated with disease risk in recent analyses from the Psychiatric Genomics Consortium.
      Title: Antipsychotic pharmacogenomics in first episode psychosis: a role for glutamate genes.
    8. findings suggest a possible role of GRID2 in the susceptibility to develop mevalonate kinase deficiency. GRID2 gene associated with MKD: The rs1450500 SNP was differently distributed in patients with MKD with respect to those with recurrent fever.
      Title: GRID2 a novel gene possibly associated with mevalonate kinase deficiency.
    9. We demonstrated for the first time GRID2 expression and localization in human and murine retina, providing evidence for a novel functional role of GRID2 in the retina.
      Title: Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion.
    10. GRID2 point mutations: cerebellar ataxia is the core phenotype, but with variable severity ranging from very mild adult-onset to congenital-onset linked to both the heterozygous and homozygous state of the variant, and the position of the mutation.
      Title: GRID2 mutations span from congenital to mild adult-onset cerebellar ataxia.
    Submit: New GeneRIF Correction See all GeneRIFs (19)

    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
    Autosomal recessive spinocerebellar ataxia 18
    MedGen: C4015505 OMIM: 616204 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC117022, MGC117023, MGC117024

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables PDZ domain binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables glutamate receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables scaffold protein binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    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 cerebellar granule cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in excitatory postsynaptic potential ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in excitatory synapse assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in glutamate receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules ISS
    Inferred from Sequence or Structural Similarity
    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 positive regulation of long-term synaptic depression IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of synapse assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in prepulse inhibition ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein localization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of neuron apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of neuron projection development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of postsynaptic density assembly IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of postsynaptic membrane neurotransmitter receptor levels IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of presynapse assembly IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in synaptic transmission, glutamatergic IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in synaptic transmission, glutamatergic ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in dendritic spine ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of ionotropic glutamate receptor complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in parallel fiber to Purkinje cell synapse IEA
    Inferred from Electronic Annotation
    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
    		  
    is_active_in postsynaptic density membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in synapse ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    glutamate receptor ionotropic, delta-2
    Names
    gluR delta-2 subunit
    glutamate receptor delta-2 subunit
    glutamate receptor, ionotropic, delta 2

    NCBI Reference Sequences (RefSeq)

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    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_034113.2 RefSeqGene

      Range
      5002..1475602
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001286838.1 → NP_001273767.1  glutamate receptor ionotropic, delta-2 isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AB209318, AC104077, AW295056, BC099653, BC099654
      Consensus CDS
      CCDS68758.1
      UniProtKB/TrEMBL
      A0A087X043
      Related
      ENSP00000421257.1, ENST00000510992.5
      Conserved Domains (3) summary
      cd13731
      Location:345 → 711
      PBP2_iGluR_delta_2; The ligand-binding domain of an orphan ionotropic glutamate receptor delta-2, a member of the type 2 periplasmic-binding fold protein superfamily
      pfam00060
      Location:473 → 747
      Lig_chan; Ligand-gated ion channel
      cl10011
      Location:28 → 332
      Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily

    2. NM_001510.4 → NP_001501.2  glutamate receptor ionotropic, delta-2 isoform 1 precursor

      See identical proteins and their annotated locations for NP_001501.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AB209318, AC104077, AC112695, AW295056, BC099653
      Consensus CDS
      CCDS3637.1
      UniProtKB/Swiss-Prot
      E9PH24, O43424, Q4KKU8, Q4KKU9, Q4KKV0, Q59FZ1
      UniProtKB/TrEMBL
      A0A087X043
      Related
      ENSP00000282020.4, ENST00000282020.9
      Conserved Domains (2) summary
      cd13731
      Location:440 → 806
      PBP2_iGluR_delta_2; The ligand-binding domain of an orphan ionotropic glutamate receptor delta-2, a member of the type 2 periplasmic-binding fold protein superfamily
      cd06391
      Location:28 → 429
      PBP1_iGluR_delta_2; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the delta2 receptor of an orphan glutamate receptor family

    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_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      92303966..93810456
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047450133.1 → XP_047306089.1  glutamate receptor ionotropic, delta-2 isoform X7

    2. XM_024454024.2 → XP_024309792.1  glutamate receptor ionotropic, delta-2 isoform X2

      UniProtKB/TrEMBL
      A0A087X043
      Conserved Domains (2) summary
      cd06391
      Location:28 → 443
      PBP1_iGluR_delta_2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the delta2 receptor of an orphan glutamate receptor family
      cd13731
      Location:456 → 822
      PBP2_iGluR_delta_2; The ligand-binding domain of an orphan ionotropic glutamate receptor delta-2, a member of the type 2 periplasmic-binding fold protein superfamily

    3. XM_017008122.3 → XP_016863611.1  glutamate receptor ionotropic, delta-2 isoform X9

    4. XM_017008120.3 → XP_016863609.1  glutamate receptor ionotropic, delta-2 isoform X5

      UniProtKB/TrEMBL
      A0A087X043

    5. XM_047450132.1 → XP_047306088.1  glutamate receptor ionotropic, delta-2 isoform X6

    6. XM_011531893.3 → XP_011530195.2  glutamate receptor ionotropic, delta-2 isoform X1

      UniProtKB/TrEMBL
      A0A087X043

    7. XM_017008118.2 → XP_016863607.1  glutamate receptor ionotropic, delta-2 isoform X3

      UniProtKB/TrEMBL
      A0A087X043

    8. XM_017008121.2 → XP_016863610.1  glutamate receptor ionotropic, delta-2 isoform X8

    9. XM_017008127.2 → XP_016863616.1  glutamate receptor ionotropic, delta-2 isoform X14

    10. XM_017008119.2 → XP_016863608.1  glutamate receptor ionotropic, delta-2 isoform X4

      UniProtKB/TrEMBL
      A0A087X043
      Related
      ENSP00000483084.1, ENST00000611049.4

    11. XM_047450134.1 → XP_047306090.1  glutamate receptor ionotropic, delta-2 isoform X11

    12. XM_047450135.1 → XP_047306091.1  glutamate receptor ionotropic, delta-2 isoform X11

    13. XM_047450136.1 → XP_047306092.1  glutamate receptor ionotropic, delta-2 isoform X11

    14. XM_011531894.3 → XP_011530196.1  glutamate receptor ionotropic, delta-2 isoform X10

      UniProtKB/TrEMBL
      A0A087X043
      Conserved Domains (3) summary
      cd13731
      Location:212 → 578
      PBP2_iGluR_delta_2; The ligand-binding domain of an orphan ionotropic glutamate receptor delta-2, a member of the type 2 periplasmic-binding fold protein superfamily
      pfam00060
      Location:340 → 614
      Lig_chan; Ligand-gated ion channel
      cl10011
      Location:2 → 199
      Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily

    15. XM_024454025.2 → XP_024309793.1  glutamate receptor ionotropic, delta-2 isoform X12

      Conserved Domains (2) summary
      cd13731
      Location:121 → 487
      PBP2_iGluR_delta_2; The ligand-binding domain of an orphan ionotropic glutamate receptor delta-2, a member of the type 2 periplasmic-binding fold protein superfamily
      cl10011
      Location:1 → 108
      Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily

    16. XM_047450137.1 → XP_047306093.1  glutamate receptor ionotropic, delta-2 isoform X13

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      95630513..97125831
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054349824.1 → XP_054205799.1  glutamate receptor ionotropic, delta-2 isoform X7

    2. XM_054349819.1 → XP_054205794.1  glutamate receptor ionotropic, delta-2 isoform X2

    3. XM_054349826.1 → XP_054205801.1  glutamate receptor ionotropic, delta-2 isoform X9

    4. XM_054349822.1 → XP_054205797.1  glutamate receptor ionotropic, delta-2 isoform X5

    5. XM_054349823.1 → XP_054205798.1  glutamate receptor ionotropic, delta-2 isoform X6

    6. XM_054349818.1 → XP_054205793.1  glutamate receptor ionotropic, delta-2 isoform X1

    7. XM_054349820.1 → XP_054205795.1  glutamate receptor ionotropic, delta-2 isoform X3

    8. XM_054349825.1 → XP_054205800.1  glutamate receptor ionotropic, delta-2 isoform X8

    9. XM_054349833.1 → XP_054205808.1  glutamate receptor ionotropic, delta-2 isoform X14

    10. XM_054349821.1 → XP_054205796.1  glutamate receptor ionotropic, delta-2 isoform X4

    11. XM_054349828.1 → XP_054205803.1  glutamate receptor ionotropic, delta-2 isoform X11

    12. XM_054349829.1 → XP_054205804.1  glutamate receptor ionotropic, delta-2 isoform X11

    13. XM_054349830.1 → XP_054205805.1  glutamate receptor ionotropic, delta-2 isoform X11

    14. XM_054349827.1 → XP_054205802.1  glutamate receptor ionotropic, delta-2 isoform X10

    15. XM_054349831.1 → XP_054205806.1  glutamate receptor ionotropic, delta-2 isoform X12

    16. XM_054349832.1 → XP_054205807.1  glutamate receptor ionotropic, delta-2 isoform X13

    RNA

    1. XR_008486971.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43424.2 GenPept UniProtKB/Swiss-Prot:O43424

    Gene LinkOut

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

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    Molecular Biology Databases
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