GAD1 (glutamate decarboxylase 1)

Gene

• Entrez ID: 2571
• Gene name: Glutamate decarboxylase 1
• Gene symbol: GAD1
• Synonyms: CPSQ1, DEE89, GAD, SCP
• Chromosome: 2
• Chromosome location: 2q31.1
• 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 autoantigen and an autoreactive T cell target in insulin-dependent diabetes. This gene may also play a role in the stiff man syndrome. Deficiency in this enzyme has been shown to lead to pyridoxine dependency with seizures. Alternative splicing of this gene results in two products, the predominant 67-kD form and a less-frequent 25-kD form. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121918345	C>G,T	Pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs774953382	C>G,T	Likely-pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant
rs1575446166	T>G	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant

Transcription factors

Transcription factor	Regulation	Reference
ARNT	Unknown	18335162
DNMT1	Repression	19029285
HDAC1	Repression	19029285
MECP2	Repression	19029285
XBP1	Unknown	18335162

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004351	Function	Glutamate decarboxylase activity	IDA	10671565
GO:0005515	Function	Protein binding	IPI	10671565, 16189514, 17474147, 21516116, 25416956, 26871637, 31515488, 32296183
GO:0005886	Component	Plasma membrane	TAS
GO:0005938	Component	Cell cortex	IEA
GO:0006538	Process	Glutamate catabolic process	TAS	10671565
GO:0006540	Process	Glutamate decarboxylation to succinate	TAS	1549570
GO:0007268	Process	Chemical synaptic transmission	TAS	8954991
GO:0007269	Process	Neurotransmitter secretion	TAS
GO:0009449	Process	Gamma-aminobutyric acid biosynthetic process	IEA
GO:0012506	Component	Vesicle membrane	NAS	10671565
GO:0016595	Function	Glutamate binding	IEA
GO:0018352	Process	Protein-pyridoxal-5-phosphate linkage	TAS	10671565
GO:0030170	Function	Pyridoxal phosphate binding	IEA
GO:0035176	Process	Social behavior	IEA
GO:0035641	Process	Locomotory exploration behavior	IEA
GO:0042136	Process	Neurotransmitter biosynthetic process	IEA
GO:0042493	Process	Response to drug	IEA
GO:0043679	Component	Axon terminus	IEA
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0047485	Function	Protein N-terminus binding	IEA
GO:0048786	Component	Presynaptic active zone	IEA
GO:0060077	Component	Inhibitory synapse	IEA
GO:0061202	Component	Clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane	TAS

Other IDs

• MIM: 605363
• HGNC: 4092
• e!Ensembl: ENSG00000128683

Protein

• UniProt ID: Q99259
• Protein name: Glutamate decarboxylase 1 (EC 4.1.1.15) (67 kDa glutamic acid decarboxylase) (GAD-67) (Glutamate decarboxylase 67 kDa isoform)
• Protein function: Catalyzes the production of GABA.
• PDB: 2OKJ, 3VP6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00282	Pyridoxal_deC	144 → 518	Pyridoxal-dependent decarboxylase conserved domain	Domain

• Sequence:

  MASSTPSSSATSSNAGADPNTTNLRPTTYDTWCGVAHGCTRKLGLKICGFLQRTNSLEEK
  SRLVSAFKERQSSKNLLSCENSDRDARFRRTETDFSNLFARDLLPAKNGEEQTVQFLLEV
  VDILLNYVRKTFDRSTKVLDFHHPHQLLEGMEGFNLELSDHPESLEQILVDCRDTLKYGV
  RTGHPRFFNQLSTGLDIIGLAGEWLTSTANTNMFTYEIAPVFVLMEQITLKKMREIVGWS
  SKDGDGIFSPGGAISNMYSIMAARYKYFPEVKTKGMAAVPKLVLFTSEQSHYSIKKAGAA
  LGFGTDNVILIKCNERGKIIPADFEAKILEAKQKGYVPFYVNATAGTTVYGAFDPIQEIA
  DICEKYNLWLHVDAAWGGGLLMSRKHRHKLNGIERANSVTWNPHKMMGVLLQCSAILVKE
  KGILQGCNQMCAGYLFQPDKQYDVSYDTGDKAIQCGRHVDIFKFWLMWKAKGTVGFENQI
  NKCLELAEYLYAKIKNREEFEMVFNGEPEHTNVCFWYIPQSLRGVPDSPQRREKLHKVAP
  KIKALMMESGTTMVGYQPQGDKANFFRMVISNPAATQSDIDFLIEEIERLGQDL

• Sequence length: 594