GABRA2 gamma-aminobutyric acid (GABA) A receptor, alpha 2 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: GABRA2provided by HGNC
Official Full Name: gamma-aminobutyric acid (GABA) A receptor, alpha 2provided by HGNC
Primary source: HGNC:4076
See related: Ensembl:ENSG00000151834; HPRD:11747; MIM:137140; Vega:OTTHUMG00000044266
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
Summary: GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 4p12

Sequence :: Chromosome: 4; NC_000004.11 (46251575..46392056, complement)

See GABRA2 in Epigenomics, MapViewer

Chromosome 4 - NC_000004.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

The gene for the GABA-A receptor alpha-2 subunit, the G allele of the SNP rs11503014 was associated with high cocaine cue-reactivity.
Title: Genetic association of GABA-A receptor alpha-2 and mu opioid receptor with cocaine cue-reactivity: evidence for inhibitory synaptic neurotransmission involvement in cocaine dependence.
This study revealed a positive correlation, among women, between BMI and the GABRA2 genotype, previously associated with both conduct problems and substance dependence.
Title: GABRA2 genotype, impulsivity, and body mass.
There is evidence that variants in the GABRA2 gene are associated with alcoholism.
Title: Gamma-aminobutyric acid A receptor, α-2 (GABRA2) variants as individual markers for alcoholism: a meta-analysis.
GABRA2 genotype, as well as the number of intake drug abuse problems and a younger age, were associated with an increased risk of relapse
Title: GABRA2 and KIBRA genotypes predict early relapse to substance use.
results suggest that GABRA2 genetic variation is associated with Impulsiveness through variation of insula activity responses.
Title: Impulsiveness and insula activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism.
GABRA2 alleles affect the subjective responses to alcohol, and suggest that the genetic variations in GABRA2 might play a role in the risk of alcohol use disorders by moderating the subjective effects of alcohol.
Title: Role of GABRA2 in moderating subjective responses to alcohol.
a highly significant difference was shown between alcohol dependence subjects and controls in the frequency of a single nucleotide polymorphisms GABRA2 haplotype
Title: GABRG1 and GABRA2 variation associated with alcohol dependence in African Americans.
In subjects with schizophrenia, mean GABA(A) alpha2 receptor subunit mRNA expression is 14% higher in layer 2 of the dorsolateral prefrontal cortex.
Title: Lamina-specific alterations in cortical GABA(A) receptor subunit expression in schizophrenia.
An interaction between allelic variation in GABRA2 and BDNF genes was associated with GM volumes, suggesting that inherited variation in these genes may promote early developmental differences in neuronal proliferation of the cerebellum.
Title: Cerebellum volume in high-risk offspring from multiplex alcohol dependence families: association with allelic variation in GABRA2 and BDNF.
Data indicate the selectivity of some selected compounds were assessed in recombinant alpha(1)beta(2)gamma(2)L, alpha(2)beta(1)gamma(2)L, and alpha(5)beta(2)gamma(2)L GABA(A) receptors.
Title: New insight into the central benzodiazepine receptor-ligand interactions: design, synthesis, biological evaluation, and molecular modeling of 3-substituted 6-phenyl-4H-imidazo[1,5-a][1,4]benzodiazepines and related compounds.

Submit: New GeneRIF Correction See all (49)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description
BioGRID:108829	BioGRID:115083	HDAC9		BioGRID	PubMed	Negative Genetic
BioGRID:108829	BioGRID:119007	UBQLN1		BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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GABA A receptor activation, organism-specific biosystem (from REACTOME)
GABA A receptor activation, organism-specific biosystemGABA B receptors are G protein coupled receptors that are activated by GABA binding to the B1 subunit and B2 subunit alters the activity of adenylate cyclase by interacting with the G alpha i/alpha 0...
GABA receptor activation, organism-specific biosystem (from REACTOME)
GABA receptor activation, organism-specific biosystemGamma aminobutyric acid (GABA) receptors are the major inhibitory receptors in human synapses. They are of two types. GABA A receptors are fast-acting ligand gated chloride ion channels that mediate ...
GABAergic synapse, organism-specific biosystem (from KEGG)
GABAergic synapse, organism-specific biosystemGamma aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the mammalian central nervous system (CNS). When released in the synaptic cleft, GABA binds to three major classes o...
GABAergic synapse, conserved biosystem (from KEGG)
GABAergic synapse, conserved biosystemGamma aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the mammalian central nervous system (CNS). When released in the synaptic cleft, GABA binds to three major classes o...
Ion channel transport, organism-specific biosystem (from REACTOME)
Ion channel transport, organism-specific biosystemIon channels mediate the flow of ions across the plasma membrane of cells. They are integral membrane proteins, typically a multimer of proteins, which, when arranged in the membrane, create a pore f...
Ligand-gated ion channel transport, organism-specific biosystem (from REACTOME)
Ligand-gated ion channel transport, organism-specific biosystemLigand-gated ion channels (LGICs) are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger (Purves, 2001).
Morphine addiction, organism-specific biosystem (from KEGG)
Morphine addiction, organism-specific biosystemMorphine is an alkaloid from the plant extracts of opium poppy. Although morphine is highly effective for the treatment of pain, it is also known to be intensely addictive. We now know that the most ...
Morphine addiction, conserved biosystem (from KEGG)
Morphine addiction, conserved biosystemMorphine is an alkaloid from the plant extracts of opium poppy. Although morphine is highly effective for the treatment of pain, it is also known to be intensely addictive. We now know that the most ...
Neuroactive ligand-receptor interaction, organism-specific biosystem (from KEGG)
Neuroactive ligand-receptor interaction, organism-specific biosystem
Neuroactive ligand-receptor interaction
Neuroactive ligand-receptor interaction, conserved biosystem (from KEGG)
Neuroactive ligand-receptor interaction, conserved biosystem
Neuroactive ligand-receptor interaction
Neuronal System, organism-specific biosystem (from REACTOME)
Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell, organism-specific biosystem (from REACTOME)
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell, organism-specific biosystemThe neurotransmitter in the synaptic cleft released by the pre-synaptic neuron binds specific receptors located on the post-synaptic terminal. These receptors are either ion channels or G protein cou...
Nicotine addiction, organism-specific biosystem (from KEGG)
Nicotine addiction, organism-specific biosystemNicotine is one of the main psychoactive ingredients in tobacco that contributes to the harmful tobacco smoking habit. A common feature of addictive drugs, including nicotine, is that they increase d...
Nicotine addiction, conserved biosystem (from KEGG)
Nicotine addiction, conserved biosystemNicotine is one of the main psychoactive ingredients in tobacco that contributes to the harmful tobacco smoking habit. A common feature of addictive drugs, including nicotine, is that they increase d...
Retrograde endocannabinoid signaling, organism-specific biosystem (from KEGG)
Retrograde endocannabinoid signaling, organism-specific biosystemEndogenous cannabinoids (endocannabinoids) serve as retrograde messengers at synapses in various regions of the brain. The family of endocannabinoids includes at least five derivatives of arachidonic...
Retrograde endocannabinoid signaling, conserved biosystem (from KEGG)
Retrograde endocannabinoid signaling, conserved biosystemEndogenous cannabinoids (endocannabinoids) serve as retrograde messengers at synapses in various regions of the brain. The family of endocannabinoids includes at least five derivatives of arachidonic...
Transmembrane transport of small molecules, organism-specific biosystem (from REACTOME)
Transmembrane transport of small molecules, organism-specific biosystem
Transmembrane transport of small molecules
Transmission across Chemical Synapses, organism-specific biosystem (from REACTOME)
Transmission across Chemical Synapses, organism-specific biosystemChemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron,...

General gene information

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Markers

D4S396 (e-PCR), detects polymorphism
- UniSTS:2568

GABRA2_1265 (e-PCR)
- UniSTS:277263

GABRA2_v365 (e-PCR)
- UniSTS:277263

SHGC-79649 (e-PCR)
- UniSTS:101406

SHGC-67786 (e-PCR)
- UniSTS:75907

D4S3229 (e-PCR)
- UniSTS:30893

D4S396 (e-PCR), detects polymorphism
- UniSTS:50614

RH106542 (e-PCR)
- UniSTS:209619

D4S401 (e-PCR), detects polymorphism
- UniSTS:66806

D4S401 (e-PCR), detects polymorphism
- UniSTS:37623

Genotypes

See GABRA2 SNP Geneview Report
See GABRA2 SNP Genotype Report
See GABRA2 SNP Variation Viewer Report

Homology

Homologs of the GABRA2 gene: The GABRA2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
GABA-A receptor activity	IEA Inferred from Electronic Annotation more info
benzodiazepine receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
chloride channel activity	IEA Inferred from Electronic Annotation more info
extracellular ligand-gated ion channel activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
gamma-aminobutyric acid signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
ion transmembrane transport	TAS Traceable Author Statement more info
neurotransmitter transport	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of neurotransmitter levels	IMP Inferred from Mutant Phenotype more info	PubMed
synaptic transmission	TAS Traceable Author Statement more info
transmembrane transport	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
axon	IEA Inferred from Electronic Annotation more info
cell junction	IEA Inferred from Electronic Annotation more info
chloride channel complex	IEA Inferred from Electronic Annotation more info
integral to synaptic vesicle membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
postsynaptic membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: gamma-aminobutyric acid receptor subunit alpha-2

Names: gamma-aminobutyric acid receptor subunit alpha-2; GABA(A) receptor, alpha 2; GABA(A) receptor subunit alpha-2

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.

Genomic

NG_012835.1 RefSeqGene

Range

5001..145482

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000807.2 → NP_000798.2 gamma-aminobutyric acid receptor subunit alpha-2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the same isoform as variant 2.

Source sequence(s)

AB209295, AC095060, BX108394

Consensus CDS

CCDS3471.1

UniProtKB/TrEMBL

A8K0U7

UniProtKB/Swiss-Prot

P47869

Related

ENSP00000371033, OTTHUMP00000125268, ENST00000381620, OTTHUMT00000216879

Conserved Domains (2) summary

pfam02931
Location:43 – 250
Blast Score: 504

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:257 – 343
Blast Score: 364

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region
NM_001114175.1 → NP_001107647.1 gamma-aminobutyric acid receptor subunit alpha-2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate 5' UTR, as compared to variant 1.

Source sequence(s)

AK125179, BX108394

Consensus CDS

CCDS3471.1

UniProtKB/TrEMBL

A8K0U7

UniProtKB/Swiss-Prot

P47869

Related

ENSP00000348897, OTTHUMP00000125269, ENST00000356504, OTTHUMT00000216880

Conserved Domains (2) summary

pfam02931
Location:43 – 250
Blast Score: 504

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:257 – 343
Blast Score: 364

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000004.11 Reference GRCh37.p10 Primary Assembly

Range

46251575..46392056, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000136.1 Alternate HuRef

Range

45569699..45710166, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018915.1 Alternate CHM1_1.0

Range

46131593..46271867, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01014324.1 (30154..170621)	None
genomic	AC093745.3	AAY40994.1
genomic	AC095060.3	None
genomic	AC104072.3 (75172..112494)	None
genomic	AMYH01014155.1 (191165..239041)	None
genomic	AMYH01014156.1	None
genomic	CH471069.1	EAW93022.1
		EAW93023.1
		EAW93024.1
		EAW93025.1
mRNA	AB209295.1	BAD92532.1
mRNA	AK125179.1	BAG54159.1
mRNA	AK289662.1	BAF82351.1
mRNA	AK293466.1	BAH11514.1
mRNA	AK307128.1	None
mRNA	BC022488.1	AAH22488.1
mRNA	BX108394.1	None
mRNA	S62907.1	AAB27278.1
mRNA	A28100.1	CAA01918.1
other-genetic	JF432507.1	ADZ15724.1