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 ... See more...

Aliases for GAD2 Gene

Aliases for GAD2 Gene

  • Glutamate Decarboxylase 2 2 3 4 5
  • Glutamate Decarboxylase 2 (Pancreatic Islets And Brain, 65kDa) 2 3
  • Glutamate Decarboxylase 65 KDa Isoform 3 4
  • 65 KDa Glutamic Acid Decarboxylase 3 4
  • EC 4.1.1.15 4 54
  • GAD-65 3 4
  • GAD65 3 4
  • Glutamate Decarboxylase 2 (Pancreatic Islets And Brain, 65kD) 2
  • Glutamate Decarboxylase-2 (Pancreas) 3
  • EC 4.1.1 54

External Ids for GAD2 Gene

Previous GeneCards Identifiers for GAD2 Gene

  • GC10P026240
  • GC10P026655
  • GC10P026509
  • GC10P026508
  • GC10P026545

Summaries for GAD2 Gene

Entrez Gene Summary for GAD2 Gene

  • 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]

GeneCards Summary for GAD2 Gene

GAD2 (Glutamate Decarboxylase 2) is a Protein Coding gene. Diseases associated with GAD2 include Stiff-Person Syndrome and Autoimmune Polyendocrine Syndrome, Type Ii. Among its related pathways are Transmission across Chemical Synapses and Alanine and aspartate metabolism. Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity and carboxy-lyase activity. An important paralog of this gene is GAD1.

UniProtKB/Swiss-Prot Summary for GAD2 Gene

Gene Wiki entry for GAD2 Gene

Additional gene information for GAD2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GAD2 Gene

Genomics for GAD2 Gene

GeneHancer (GH) Regulatory Elements for GAD2 Gene

Promoters and enhancers for GAD2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH10J026216 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE 750.6 -0.1 -106 0.8 ZNF785 GLIS2 REST ZBTB8A ZEB2 PATZ1 POLR2A ZNF501 ZNF692 SP2 GAD2 lnc-ABI1-10 NONHSAG005433.2
GH10J026218 Promoter/Enhancer 0.8 Ensembl ENCODE 750.6 +1.7 1704 0.4 POLR2A EZH2 ZNF335 CBX8 GAD2 lnc-ABI1-10 piR-35674-045
GH10J026213 Enhancer 0.7 FANTOM5 Ensembl ENCODE 754 -1.9 -1867 1.1 EZH2 NANOG GAD2 lnc-ABI1-10 MYO3A NONHSAG005433.2
GH10J026220 Promoter 0.6 EPDnew 750.6 +0.4 448 0.1 ZNF785 POLR2A ZBTB20 EZH2 ZNF335 GAD2 lnc-ABI1-10 piR-35674-045
GH10J026215 Enhancer 0.3 ENCODE 750.6 -1.1 -1120 0.2 EZH2 GAD2 lnc-ABI1-10 NONHSAG005433.2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GAD2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the GAD2 gene promoter:
  • Evi-1
  • HNF-1
  • HNF-1A
  • HOXA9
  • HOXA9B
  • HSF2
  • Meis-1
  • Meis-1b
  • NRSF form 1
  • NRSF form 2

Genomic Locations for GAD2 Gene

Genomic Locations for GAD2 Gene
chr10:26,216,307-26,304,562
(GRCh38/hg38)
Size:
88,256 bases
Orientation:
Plus strand
chr10:26,505,236-26,593,491
(GRCh37/hg19)
Size:
88,256 bases
Orientation:
Plus strand

Genomic View for GAD2 Gene

Genes around GAD2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GAD2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GAD2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GAD2 Gene

Proteins for GAD2 Gene

  • Protein details for GAD2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q05329-DCE2_HUMAN
    Recommended name:
    Glutamate decarboxylase 2
    Protein Accession:
    Q05329
    Secondary Accessions:
    • Q9UD87

    Protein attributes for GAD2 Gene

    Size:
    585 amino acids
    Molecular mass:
    65411 Da
    Cofactor:
    Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
    Quaternary structure:
    • Homodimer.
    SequenceCaution:
    • Sequence=CAA49554.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for GAD2 Gene

neXtProt entry for GAD2 Gene

Selected DME Specific Peptides for GAD2 Gene

Q05329:
  • NEERMSRLSKVAPVIKARMME
  • TLKKMREI
  • SYDTGDK
  • ATAGTTVYGAFDP
  • NFFRMVISNPAAT
  • GDGIFSPGG
  • TANTNMFTYEIAPVF
  • HVDAAWGGGLLMS
  • LHATDLLPAC
  • YLFQQDK
  • FTSEHSH
  • KCLELAEYLY
  • DAAWGGGLLMSRKH
  • SVTWNPHK
  • EKPAESGGS
  • VPFLVSAT
  • RLSKVAPV
  • IIKNREGYEMVFDGKPQHTNVCFW
  • FNQLSTGLD
  • KMREIIGW

Post-translational modifications for GAD2 Gene

  • Phosphorylated; which does not affect kinetic parameters or subcellular location.
  • Palmitoylated; which is required for presynaptic clustering.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for GAD2 Gene

Antibody Products

Domains & Families for GAD2 Gene

Gene Families for GAD2 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for GAD2 Gene

Suggested Antigen Peptide Sequences for GAD2 Gene

GenScript: Design optimal peptide antigens:
  • Glutamate decarboxylase 65 kDa isoform (DCE2_HUMAN)
  • GAD2 protein (Q4G154_HUMAN)
  • Glutamate decarboxylase 2 (Pancreatic islets and brain, 65kDa), isoform CRA_b (Q5VZ30_HUMAN)
  • Glutamic acid decarboxylase (Q9UGI5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q05329

UniProtKB/Swiss-Prot:

DCE2_HUMAN :
  • Belongs to the group II decarboxylase family.
Family:
  • Belongs to the group II decarboxylase family.
genes like me logo Genes that share domains with GAD2: view

Function for GAD2 Gene

Molecular function for GAD2 Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the production of GABA.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H(+) + L-glutamate = 4-aminobutanoate + CO2; Xref=Rhea:RHEA:17785, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:29985, ChEBI:CHEBI:59888; EC=4.1.1.15;.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=2.15 mM for glutamate {ECO:0000269 PubMed:8999827};
GENATLAS Biochemistry:
glutamate decarboxylase 2,islet beta cell,65kDa autoantigen in insulin-dependent diabetes mellitus and immunogen for autoreactive B cells

Enzyme Numbers (IUBMB) for GAD2 Gene

Phenotypes From GWAS Catalog for GAD2 Gene

Gene Ontology (GO) - Molecular Function for GAD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0004351 glutamate decarboxylase activity IEA --
GO:0005515 protein binding IPI 10671565
GO:0016595 glutamate binding IEA --
GO:0016829 lyase activity IEA --
genes like me logo Genes that share ontologies with GAD2: view
genes like me logo Genes that share phenotypes with GAD2: view

Animal Models for GAD2 Gene

MGI Knock Outs for GAD2:
  • Gad2 Gad2<tm1Oba>
  • Gad2 Gad2<tm1b(EUCOMM)Wtsi>
  • Gad2 Gad2<tm1Bae>
  • Gad2 Gad2<tm1Miya>

Animal Model Products

  • Taconic Biosciences Mouse Models for GAD2

CRISPR Products

Clone Products

  • Addgene plasmids for GAD2

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for GAD2 Gene

Localization for GAD2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GAD2 Gene

Cytoplasm, cytosol. Cytoplasmic vesicle. Cell junction, synapse, presynaptic cell membrane; Lipid-anchor. Golgi apparatus membrane; Peripheral membrane protein; Cytoplasmic side. Note=Associated to cytoplasmic vesicles. In neurons, cytosolic leaflet of Golgi membranes and presynaptic clusters.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GAD2 gene
Compartment Confidence
plasma membrane 4
cytosol 4
nucleus 3
golgi apparatus 3
mitochondrion 2
extracellular 1
cytoskeleton 1

Gene Ontology (GO) - Cellular Components for GAD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005737 cytoplasm IEA --
GO:0005794 Golgi apparatus IEA --
GO:0005829 cytosol IEA --
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with GAD2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for GAD2 Gene

Pathways & Interactions for GAD2 Gene

genes like me logo Genes that share pathways with GAD2: view

Gene Ontology (GO) - Biological Process for GAD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006540 glutamate decarboxylation to succinate IEA,TAS --
GO:0007268 chemical synaptic transmission TAS 8954991
GO:0007269 neurotransmitter secretion TAS --
GO:0019752 carboxylic acid metabolic process IEA --
GO:0042136 neurotransmitter biosynthetic process IEA --
genes like me logo Genes that share ontologies with GAD2: view

No data available for SIGNOR curated interactions for GAD2 Gene

Drugs & Compounds for GAD2 Gene

(35) Drugs for GAD2 Gene - From: DrugBank, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phenelzine Approved Pharma Target, inhibitor 10
Glutamic acid Approved Nutra Full agonist, Agonist, Target 281
Pyridoxal Phosphate Approved, Investigational Nutra Target, cofactor 22
Carbon dioxide Approved, Investigational, Vet_approved Pharma 0
Famotidine Approved Pharma Histamine H2-receptor antagonist 70

(12) Additional Compounds for GAD2 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Cysteic acid
  • 3-Sulfoalanine
  • beta-Sulfoalanine
  • Cysteine sulfonic acid
  • 3-Sulphoalanine
  • Cysteate
498-40-8
genes like me logo Genes that share compounds with GAD2: view

Transcripts for GAD2 Gene

mRNA/cDNA for GAD2 Gene

CRISPR Products

Clone Products

  • Addgene plasmids for GAD2

Alternative Splicing Database (ASD) splice patterns (SP) for GAD2 Gene

No ASD Table

Relevant External Links for GAD2 Gene

GeneLoc Exon Structure for
GAD2
ECgene alternative splicing isoforms for
GAD2

Expression for GAD2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for GAD2 Gene

mRNA differential expression in normal tissues according to GTEx for GAD2 Gene

This gene is overexpressed in Brain - Nucleus accumbens (basal ganglia) (x10.4), Brain - Putamen (basal ganglia) (x8.4), Brain - Caudate (basal ganglia) (x8.0), Brain - Hypothalamus (x5.9), and Brain - Anterior cingulate cortex (BA24) (x4.5).

Protein differential expression in normal tissues from HIPED for GAD2 Gene

This gene is overexpressed in Frontal cortex (22.5), Brain (14.8), Retina (14.0), and Islet of Langerhans (13.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for GAD2 Gene



Protein tissue co-expression partners for GAD2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of GAD2 Gene:

GAD2

SOURCE GeneReport for Unigene cluster for GAD2 Gene:

Hs.231829

Evidence on tissue expression from TISSUES for GAD2 Gene

  • Pancreas(4.9)
  • Nervous system(3.4)
  • Blood(2.1)
  • Eye(2)
genes like me logo Genes that share expression patterns with GAD2: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for GAD2 Gene

Orthologs for GAD2 Gene

This gene was present in the common ancestor of animals.

Orthologs for GAD2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GAD2 33 32
  • 99.32 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GAD2 33 32
  • 92.19 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GAD2 33
  • 92 (a)
OneToOne
cow
(Bos Taurus)
Mammalia GAD2 33 32
  • 91.74 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Gad2 17 33 32
  • 90.09 (n)
rat
(Rattus norvegicus)
Mammalia Gad2 32
  • 89.12 (n)
oppossum
(Monodelphis domestica)
Mammalia GAD2 33
  • 86 (a)
OneToOne
chicken
(Gallus gallus)
Aves GAD2 33 32
  • 85.02 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GAD2 33
  • 87 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia gad2 32
  • 76.18 (n)
zebrafish
(Danio rerio)
Actinopterygii gad2 33 32
  • 73.29 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Gad1 33 34
  • 53 (a)
OneToMany
b 34
  • 46 (a)
worm
(Caenorhabditis elegans)
Secernentea unc-25 33 34
  • 52 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.19 33
  • 54 (a)
OneToMany
Species where no ortholog for GAD2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for GAD2 Gene

ENSEMBL:
Gene Tree for GAD2 (if available)
TreeFam:
Gene Tree for GAD2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GAD2: view image

Paralogs for GAD2 Gene

Paralogs for GAD2 Gene

(5) SIMAP similar genes for GAD2 Gene using alignment to 5 proteins:

  • DCE2_HUMAN
  • Q4G154_HUMAN
  • Q5VZ29_HUMAN
  • Q5VZ30_HUMAN
  • Q5VZ31_HUMAN
genes like me logo Genes that share paralogs with GAD2: view

Variants for GAD2 Gene

Sequence variations from dbSNP and Humsavar for GAD2 Gene

SNP ID Clin Chr 10 pos Variation AA Info Type
rs1000033242 -- 26,243,749(+) T/C/G intron_variant
rs1000058908 -- 26,250,176(+) G/C intron_variant
rs1000079364 -- 26,295,645(+) T/C intron_variant
rs1000104601 -- 26,241,218(+) G/A intron_variant
rs1000155282 -- 26,269,610(+) C/G intron_variant

Structural Variations from Database of Genomic Variants (DGV) for GAD2 Gene

Variant ID Type Subtype PubMed ID
esv3335357 CNV insertion 20981092
esv3576316 CNV gain 25503493

Variation tolerance for GAD2 Gene

Residual Variation Intolerance Score: 19.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.84; 48.03% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GAD2 Gene

Human Gene Mutation Database (HGMD)
GAD2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GAD2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GAD2 Gene

Disorders for GAD2 Gene

MalaCards: The human disease database

(24) MalaCards diseases for GAD2 Gene - From: HGMD, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
stiff-person syndrome
  • sps
autoimmune polyendocrine syndrome, type ii
  • aps2
powassan encephalitis
  • powassan encephalitis virus infection
diabetes mellitus, ketosis-prone
  • diabetes mellitus, insulin-dependent
alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity
  • combined immunodeficiency due to partial rag1 deficiency
- elite association - COSMIC cancer census association via MalaCards
Search GAD2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GAD2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GAD2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GAD2 Gene

Publications for GAD2 Gene

  1. Association analysis of the glutamic acid decarboxylase 2 and the glutamine synthetase genes (GAD2, GLUL) with schizophrenia. (PMID: 19125103) Arai S … Fukumaki Y (Psychiatric genetics 2009) 3 23 43 56
  2. GAD2 gene sequence variations are associated with eating behaviors and weight gain in women from the Quebec family study. (PMID: 19686769) Choquette AC … Pérusse L (Physiology & behavior 2009) 3 23 43 56
  3. GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop. (PMID: 17384644) Fenalti G … Whisstock JC (Nature structural & molecular biology 2007) 3 4 23 56
  4. Mutation screen of the GAD2 gene and association study of alcoholism in three populations. (PMID: 17034009) Lappalainen J … Gelernter J (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2007) 3 23 43 56
  5. A -243A-->G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects. (PMID: 17459095) Boesgaard TW … Pedersen O (Diabetic medicine : a journal of the British Diabetic Association 2007) 3 23 43 56

Products for GAD2 Gene

Sources for GAD2 Gene