Gene Report

Basic Information

Approved Symbol	GAD1
Approved Name	glutamate decarboxylase 1 (brain, 67kDa)
Previous Symbol	GAD
Previous Name	"glutamate decarboxylase 1 (brain, 67kD)"
Location	2q31
Position	chr2:171716393-171717661 (+)
External Links	Entrez Gene: 2571 Ensembl: ENSG00000128683 UCSC: uc002ugi.3 HGNC ID: 4092
No. of Studies (Positive/Negative)	3(2/1)
Type	Literature-origin; Protein mapped

Positive relationships between GAD1 and MDD (count: 2)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
GAD1	Hettema, 2006	patients and normal controls	P-value=0.003; OR=1.23	Several of the six single-nucleotide polymorphisms tested in...... Several of the six single-nucleotide polymorphisms tested in the GAD1 region demonstrated significant association in both stages, and a combined analysis in all 1128 subjects indicated that they formed a common high-risk haplotype that was significantly over-represented in cases (P=0.003) with effect size OR=1.23 More...
GAD1	Oh DH, 2014	patients and normal controls	P-value=0.045	We found two datasets where the mRNA levels of GAD1 and SLC1...... We found two datasets where the mRNA levels of GAD1 and SLC1A2 in subregions of the dlPFC were significantly and marginally lower in subjects with MDD (n = 15) than in controls (n = 15) (p = 0.045 and 0.057, respectively) More...

Positive relationships between GAD1 and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
Name in Literature	Related Components
GAD1		SLC1A2(SLC1A2)	gene	Oh DH, 2014	patients and normal controls	P-value<0.001	the expression levels of both GAD1 and SLC1A2 mRNAs were com...... the expression levels of both GAD1 and SLC1A2 mRNAs were commonly correlated with the expression levels of several neuropathological markers in the dlPFC in all of the SNCID subjects (n = 60, p < 0.001) More...

Positive relationship network of GAD1 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between GAD1 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
GAD67	Lappalainen J, 2004	Patients and nomal controls		Comparison of SNP and haplotype frequencies between individ...... Comparison of SNP and haplotype frequencies between individuals with depression and controls revealed no differences More...

Negative relationships between GAD1 and other components at different levels (count: 0)

GAD1 related SNPs in MK4MDD (count: 0)

GAD1 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Glutamate decarboxylase 1	Q99259	2(2/0)	Literature-origin

GAD1 related GO terms (count: 19)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0004351	glutamate decarboxylase activity	molecular function	IDA[10671565]; TAS
GO:0007268	synaptic transmission	biological process	TAS

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0005622	intracellular	cellular component	IDA[10671565]
GO:0005515	protein binding	molecular function	IPI[10671565\|16189514\|17474147\|21516116\|25416956]
GO:0042493	response to drug	biological process	IEA
GO:0006538	glutamate catabolic process	biological process	TAS[10671565]
GO:0012506	vesicle membrane	cellular component	NAS[10671565]
GO:0047485	protein N-terminus binding	molecular function	IEA
GO:0006540	glutamate decarboxylation to succinate	biological process	TAS[1549570]
GO:0005886	plasma membrane	cellular component	TAS
GO:0042136	neurotransmitter biosynthetic process	biological process	IEA
GO:0046982	protein heterodimerization activity	molecular function	IEA
GO:0016595	glutamate binding	molecular function	IEA
GO:0061202	clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane	cellular component	TAS
GO:0009449	gamma-aminobutyric acid biosynthetic process	biological process	IEA
GO:0030170	pyridoxal phosphate binding	molecular function	IEA
GO:0018352	protein-pyridoxal-5-phosphate linkage	biological process	TAS[10671565]
GO:0007269	neurotransmitter secretion	biological process	TAS
GO:0048786	presynaptic active zone	cellular component	IEA

GAD1 related KEGG pathways (count: 5)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa04940	type i_diabetes_mellitus	Type I diabetes mellitus	Type I diabetes mellitus is a disease that results from auto...... Type I diabetes mellitus is a disease that results from autoimmune destruction of the insulin-producing beta-cells. Certain beta-cell proteins act as autoantigens after being processed by antigen-presenting cell (APC), such as macrophages and dendritic cells, and presented in a complex with MHC-II molecules on the surface of the APC. Then immunogenic signals from APC activate CD4+ T cells, predominantly of the Th1 subset. Antigen-activated Th1 cells produce IL-2 and IFNgamma. They activate macrophages and cytotoxic CD8+ T cells, and these effector cells may kill islet beta-cells by one or both of two types of mechanisms: (1) direct interactions of antigen-specific cytotoxic T cells with a beta-cell autoantigen-MHC-I complex on the beta-cell, and (2) non-specific inflammatory mediators, such as free radicals/oxidants and cytokines (IL-1, TNFalpha, TNFbeta, IFNgamma). Type I diabetes is a polygenic disease. One of the principle determining genetic factors in diabetes incidence is the inheritance of mutant MHC-II alleles. Another plausible candidate gene is the insulin gene. More...

ID	Name	Brief Description
Gene mapped KEGG pathways
hsa00250	alanine aspartate_and_glutamate_metabolism	Alanine, aspartate and glutamate metabolism
hsa00430	taurine and_hypotaurine_metabolism	Taurine and hypotaurine metabolism
hsa00410	beta alanine_metabolism	beta-Alanine metabolism
hsa00650	butanoate metabolism	Butanoate metabolism

GAD1 related BioCarta pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
NEUROTRANSMITTERS_PATHWAY	neurotransmitters pathway	Biosynthesis of neurotransmitters	Neurotransmitters are signaling molecules used by neurons to...... Neurotransmitters are signaling molecules used by neurons to communicate across chemical synapses. The receptors for neurotransmitters include G-protein coupled receptors (GPCRs) and ligand-gated ion channels. The biogenic amines are neurotransmitters derived from amino acids, and include dopamine, epinephrine, GABA, histamine and serotonin. For each of these, decarboxylation of an amino acid is a key step. GABA, gamma-aminobutyric acid, is a key inhibitory neurotransmitter and is synthesized through the decarboxylation of glutamate in a single step. Glutamate is itself an abundant excitatory neurotransmitter. Histamine signals are involved in inflammation and acid secretion in the stomach, acting through GPCRs. Histamine is synthesized in a single step from the amino acid histidine through decarboxylation. Serotonin is a neurotransmitter with a large range of effects, including roles in mood and depression, and is synthesized by first adding a hydroxyl group to tryptophan, followed by decarboxylation. A common mechanism of antidepressant action is to block the reuptake of serotonin at synapses. Dopamine is involved in movement and mood and is derived from tyrosine through addition of a hydroxyl group and decarboxylation. Additional reactions create norepinephrine and epinephrine from dopamine. These molecules, also called adrenalin and noradrenalin, act on the adrenergic receptors to exert responses including alteration of blood pressure, heart rate, metabolic activity, and bronchodilation. Many common drugs such as asthma and heart pressure medications act on adrenergic receptors. Alterations in these biosynthetic pathways can lead to significant clinical consequences. For example, deficiency in tyrosine hydroxylase activity leads to a movement disorder similar to Parkinson's disease and may play a role in Parkinson's disease and the development of an autoimmune response against glutamate decarboxylase (GAD) may trigger the destruction of insulin-secreting cells and type I diabetes. Numerous studies have searched for a potential genetic role of tryptophan hydroxylase mutations in neuropsychiatric indications, with conflicting results. More...

GAD1 related Reactome pathways (count: 0)

GAD1 related interactors from protein-protein interaction data in HPRD (count: 5)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
GAD1	PPP2CB	No	in vitro	15147202
GAD1	GAD2	Yes	in vivo	7836456
GAD1	PRKCE	No	in vitro;in vivo	15147202
GAD1	HAAO	No	yeast 2-hybrid	16189514
GAD1	PPP2CA	No	in vitro	15147202

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Gene mapped BioCarta pathways