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    GAD2 glutamate decarboxylase 2 [ Homo sapiens (human) ]

    Gene ID: 2572, updated on 11-Apr-2024

    Summary

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    Official Symbol
    GAD2provided by HGNC
    Official Full Name
    glutamate decarboxylase 2provided by HGNC
    Primary source
    HGNC:HGNC:4093
    See related
    Ensembl:ENSG00000136750 MIM:138275; AllianceGenome:HGNC:4093
    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
    GAD65
    Summary
    This gene encodes one of several forms of glutamic acid decarboxylase, identified as a major autoantigen in insulin-dependent diabetes. The enzyme encoded is responsible for catalyzing the production of gamma-aminobutyric acid from L-glutamic acid. A pathogenic role for this enzyme has been identified in the human pancreas since it has been identified as an autoantibody and an autoreactive T cell target in insulin-dependent diabetes. This gene may also play a role in the stiff man syndrome. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Oct 2008]
    Expression
    Restricted expression toward brain (RPKM 7.7) See more
    Orthologs
    mouse all
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    Genomic context

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    See GAD2 in Genome Data Viewer
    Location:
    10p12.1
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (26216372..26304558)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (26240884..26329300)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (26505301..26593487)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101929073 Neighboring gene NANOG hESC enhancer GRCh37_chr10:26263803-26264349 Neighboring gene myosin IIIA Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr10:26289384-26290583 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr10:26290901-26292100 Neighboring gene NANOG hESC enhancer GRCh37_chr10:26488725-26489248 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr10:26502717-26503284 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:26503285-26503850 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:26503851-26504417 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:26507027-26507655 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3164 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3165 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:26726587-26727116 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3167 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2235 Neighboring gene amyloid beta precursor protein binding family B member 1 interacting protein Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3168 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:26778915-26779063 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2236 Neighboring gene RNA, 5S ribosomal pseudogene 307 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3169 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3170 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:26868178-26868678 Neighboring gene long intergenic non-protein coding RNA 3028

    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. The plasma level of glutamic acid decarboxylase 65 (GAD65) increased in severely autistic Iranian children. Vazifekhah S, et al. Bratisl Lek Listy, 2022. PMID 35420879
    2. Similarities between bacterial GAD and human GAD65: Implications in gut mediated autoimmune type 1 diabetes. Bedi S, et al. PLoS One, 2022. PMID 35196314, Free PMC Article
    3. Neurological Syndromes Associated with Anti-GAD Antibodies. Dade M, et al. Int J Mol Sci, 2020 May 24. PMID 32456344, Free PMC Article
    4. The association between GAD65 antibody levels and incident Type 2 Diabetes Mellitus in an adult population: A meta-analysis. Koopman ADM, et al. Metabolism, 2019 Jun. PMID 30853448
    5. Reduced display of conformational epitopes in the N-terminal truncated GAD65 isoform: relevance for people with stiff person syndrome or DQ8/8-positive Type 1 diabetes mellitus. Hampe CS, et al. Diabet Med, 2019 Nov. PMID 30264481, Free PMC Article

    See all (126) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Heterogeneity of circulating CXCR5-PD-1[hi]Tph cells in patients of type 2 and type 1 diabetes in Chinese population.
      Title: Heterogeneity of circulating CXCR5-PD-1(hi)Tph cells in patients of type 2 and type 1 diabetes in Chinese population.
    2. The plasma level of glutamic acid decarboxylase 65 (GAD65) increased in severely autistic Iranian children.
      Title: The plasma level of glutamic acid decarboxylase 65 (GAD65) increased in severely autistic Iranian children.
    3. Similarities between bacterial GAD and human GAD65: Implications in gut mediated autoimmune type 1 diabetes.
      Title: Similarities between bacterial GAD and human GAD65: Implications in gut mediated autoimmune type 1 diabetes.
    4. Neurological Syndromes Associated with Anti-GAD Antibodies.
      Title: Neurological Syndromes Associated with Anti-GAD Antibodies.
    5. GAD1 but not GAD2 polymorphisms are associated with heroin addiction phenotypes.
      Title: GAD1 but not GAD2 polymorphisms are associated with heroin addiction phenotypes.
    6. This binding characteristic is probably attributable to reduced presentation of two conformational epitopes by the N-terminal truncated molecule. These findings support the notion of disease-specific GAD65Ab epitope specificities and emphasize the need to evaluate the applicability of novel assays for different medical conditions.
      Title: Reduced display of conformational epitopes in the N-terminal truncated GAD65 isoform: relevance for people with stiff person syndrome or DQ8/8-positive Type 1 diabetes mellitus.
    7. Posttransplant blood GAD65 and miR-375 performed equally well in quantifying early graft destruction and predicting graft outcome after islet transplantation in patients with type 1 diabetes.
      Title: Combined Analysis of GAD65, miR-375, and Unmethylated Insulin DNA Following Islet Transplantation in Patients With T1D.
    8. GAD65 antibody positivity was associated with an increased risk of future Type 2 Diabetes Mellitus in adults--{REVIEW}
      Title: The association between GAD65 antibody levels and incident Type 2 Diabetes Mellitus in an adult population: A meta-analysis.
    9. we show an interaction of the genetic variation rs2236418 in the GAD2 gene and sex on GABA/glutamate balance in the pregenual anterior cingulate cortex
      Title: GAD65 Promoter Polymorphism rs2236418 Modulates Harm Avoidance in Women via Inhibition/Excitation Balance in the Rostral ACC.
    10. In individuals with adult-onset diabetes, presence of N-terminally truncated GAD65 autoantibodies is associated with the clinical phenotype of autoimmune type 1 diabetes and predicts insulin therapy.
      Title: Autoantibodies to N-terminally truncated GAD improve clinical phenotyping of individuals with adult-onset diabetes: Action LADA 12.
    Submit: New GeneRIF Correction See all GeneRIFs (93)

    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

    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

    Clone Names

    • MGC161605, MGC161607

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables glutamate binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables glutamate decarboxylase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein-containing complex binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables pyridoxal phosphate binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in cellular response to brain-derived neurotrophic factor stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to hypoxia IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in chemical synaptic transmission TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in gamma-aminobutyric acid biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glutamate decarboxylation to succinate IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in response to caloric restriction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to cocaine IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to progesterone IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to xenobiotic stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in GABA-ergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in axon IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane TAS
    Traceable Author Statement
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in inhibitory synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in neuronal cell body IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in presynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in synaptic vesicle membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    glutamate decarboxylase 2
    Names
    65 kDa glutamic acid decarboxylase
    GAD-65
    Glutamate decarboxylase-2 (pancreas)
    glutamate decarboxylase 2 (pancreatic islets and brain, 65kDa)
    NP_000809.1
    NP_001127838.1

    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_000818.3 → NP_000809.1  glutamate decarboxylase 2

      See identical proteins and their annotated locations for NP_000809.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript.
      Source sequence(s)
      BI438818, BP392604, M74826
      Consensus CDS
      CCDS7149.1
      UniProtKB/Swiss-Prot
      Q05329, Q9UD87
      UniProtKB/TrEMBL
      A0A3B3IU09, Q5VZ30
      Related
      ENSP00000259271.3, ENST00000259271.7
      Conserved Domains (1) summary
      pfam00282
      Location:138 → 509
      Pyridoxal_deC; Pyridoxal-dependent decarboxylase conserved domain

    2. NM_001134366.2 → NP_001127838.1  glutamate decarboxylase 2

      See identical proteins and their annotated locations for NP_001127838.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 3' UTR, compared to variant 1.
      Source sequence(s)
      AL162503, M81882
      Consensus CDS
      CCDS7149.1
      UniProtKB/Swiss-Prot
      Q05329, Q9UD87
      UniProtKB/TrEMBL
      A0A3B3IU09, Q5VZ30
      Related
      ENSP00000365437.3, ENST00000376261.8
      Conserved Domains (1) summary
      pfam00282
      Location:138 → 509
      Pyridoxal_deC; Pyridoxal-dependent decarboxylase conserved domain

    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_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      26216372..26304558
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      26240884..26329300
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q05329.1 GenPept UniProtKB/Swiss-Prot:Q05329

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