GABRA2 (gamma-aminobutyric acid type A receptor subunit alpha2)

Gene

• Entrez ID: 2555
• Gene name: Gamma-aminobutyric acid type A receptor subunit alpha2
• Gene symbol: GABRA2
• Synonyms (NCBI Gene): DEE78, EIEE78
• Chromosome: 4
• Chromosome location: 4p12
• 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 GA

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs279836	T>A,G	Risk-factor	Intron variant
rs279845	T>A,G	Risk-factor	Intron variant
rs279871	T>C	Risk-factor	Intron variant
rs1243977956	G>A,T	Pathogenic	Synonymous variant, missense variant, coding sequence variant
rs1281490675	G>A,C	Pathogenic	Coding sequence variant, missense variant, synonymous variant
rs1560442716	T>G	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs1577800481	G>T	Pathogenic	Coding sequence variant, missense variant
rs1577975808	A>G	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT720748	hsa-miR-205-3p	HITS-CLIP	19536157
MIRT720747	hsa-miR-545-5p	HITS-CLIP	19536157
MIRT720746	hsa-miR-222-5p	HITS-CLIP	19536157
MIRT720745	hsa-miR-30a-3p	HITS-CLIP	19536157
MIRT720744	hsa-miR-30d-3p	HITS-CLIP	19536157
MIRT720743	hsa-miR-30e-3p	HITS-CLIP	19536157
MIRT720748	hsa-miR-205-3p	HITS-CLIP	19536157
MIRT720747	hsa-miR-545-5p	HITS-CLIP	19536157
MIRT720746	hsa-miR-222-5p	HITS-CLIP	19536157
MIRT720745	hsa-miR-30a-3p	HITS-CLIP	19536157
MIRT720744	hsa-miR-30d-3p	HITS-CLIP	19536157
MIRT720743	hsa-miR-30e-3p	HITS-CLIP	19536157
MIRT1009778	hsa-miR-1251	CLIP-seq
MIRT1009779	hsa-miR-216b	CLIP-seq
MIRT1009780	hsa-miR-2964a-5p	CLIP-seq
MIRT1009781	hsa-miR-3160-3p	CLIP-seq
MIRT1009782	hsa-miR-3671	CLIP-seq
MIRT1009783	hsa-miR-3675-3p	CLIP-seq
MIRT1009784	hsa-miR-4666-3p	CLIP-seq
MIRT1009785	hsa-miR-4762-5p	CLIP-seq
MIRT1009786	hsa-miR-607	CLIP-seq
MIRT1009780	hsa-miR-2964a-5p	CLIP-seq
MIRT1009781	hsa-miR-3160-3p	CLIP-seq
MIRT2437362	hsa-miR-3159	CLIP-seq
MIRT2437363	hsa-miR-3167	CLIP-seq
MIRT2437364	hsa-miR-4275	CLIP-seq
MIRT2437365	hsa-miR-556-3p	CLIP-seq
MIRT2437366	hsa-miR-876-5p	CLIP-seq
MIRT2437367	hsa-miR-944	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004888	Function	Transmembrane signaling receptor activity	IEA
GO:0004890	Function	GABA-A receptor activity	IBA
GO:0004890	Function	GABA-A receptor activity	IEA
GO:0005216	Function	Monoatomic ion channel activity	IEA
GO:0005230	Function	Extracellular ligand-gated monoatomic ion channel activity	IEA
GO:0005254	Function	Chloride channel activity	IBA
GO:0005254	Function	Chloride channel activity	IEA
GO:0005515	Function	Protein binding	IPI	35384245
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006821	Process	Chloride transport	IEA
GO:0007214	Process	Gamma-aminobutyric acid signaling pathway	IBA
GO:0007214	Process	Gamma-aminobutyric acid signaling pathway	IEA
GO:0007214	Process	Gamma-aminobutyric acid signaling pathway	IMP	8391122
GO:0007214	Process	Gamma-aminobutyric acid signaling pathway	ISS
GO:0008503	Function	Benzodiazepine receptor activity	IMP	8391122
GO:0016020	Component	Membrane	IEA
GO:0022851	Function	GABA-gated chloride ion channel activity	IBA
GO:0022851	Function	GABA-gated chloride ion channel activity	IDA	9039914
GO:0030424	Component	Axon	IEA
GO:0030425	Component	Dendrite	IEA
GO:0030659	Component	Cytoplasmic vesicle membrane	IEA
GO:0030672	Component	Synaptic vesicle membrane	IDA	8391122
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0032590	Component	Dendrite membrane	IBA
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0034707	Component	Chloride channel complex	IEA
GO:0038023	Function	Signaling receptor activity	IEA
GO:0042995	Component	Cell projection	IEA
GO:0043025	Component	Neuronal cell body	IEA
GO:0045202	Component	Synapse	IEA
GO:0045211	Component	Postsynaptic membrane	IEA
GO:0051932	Process	Synaptic transmission, GABAergic	IBA
GO:0060077	Component	Inhibitory synapse	IEA
GO:0060078	Process	Regulation of postsynaptic membrane potential	IEA
GO:0098794	Component	Postsynapse	IBA
GO:0098794	Component	Postsynapse	IEA
GO:0098982	Component	GABA-ergic synapse	IEA
GO:0099505	Process	Regulation of presynaptic membrane potential	IEA
GO:0099507	Function	Ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IDA	22711532
GO:0099507	Function	Ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IMP	22711532
GO:0099507	Function	Ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	NAS	22711532
GO:0099634	Component	Postsynaptic specialization membrane	IEA
GO:1902476	Process	Chloride transmembrane transport	IBA
GO:1902476	Process	Chloride transmembrane transport	IDA	9039914
GO:1902711	Component	GABA-A receptor complex	IBA
GO:1902711	Component	GABA-A receptor complex	IDA	9039914
GO:1902711	Component	GABA-A receptor complex	ISS
GO:1904315	Function	Transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IDA	22711532
GO:1904315	Function	Transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IMP	22711532
GO:1904862	Process	Inhibitory synapse assembly	IBA
GO:1904862	Process	Inhibitory synapse assembly	IEA
GO:1904862	Process	Inhibitory synapse assembly	ISS

Other IDs

• MIM: 137140
• HGNC: 4076
• e!Ensembl: ENSG00000151834

Protein

• UniProt ID: P47869
• Protein name: Gamma-aminobutyric acid receptor subunit alpha-2 (GABA(A) receptor subunit alpha-2) (GABAAR subunit alpha-2)
• Protein function: Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:10449790, PubMed:29961870, PubMed:31032849). GABA-gated chloride channels, also
• PDB: 9CRV, 9CSB, 9CT0, 9CTJ, 9CTV, 9CX7, 9CXB, 9CXC
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02931	Neur_chan_LBD	42 → 250	Neurotransmitter-gated ion-channel ligand binding domain	Family
  PF02932	Neur_chan_memb	257 → 344	Neurotransmitter-gated ion-channel transmembrane region	Family

• Sequence:

  MKTKLNIYNMQFLLFVFLVWDPARLVLANIQEDEAKNNITIFTRILDRLLDGYDNRLRPG
  LGDSITEVFTNIYVTSFGPVSDTDMEYTIDVFFRQKWKDERLKFKGPMNILRLNNLMASK
  IWTPDTFFHNGKKSVAHNMTMPNKLLRIQDDGTLLYTMRLTVQAECPMHLEDFPMDAHSC
  PLKFGSYAYTTSEVTYIWTYNASDSVQVAPDGSRLNQYDLLGQSIGKETIKSSTGEYTVM
  TAHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISA
  RNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGWAWDGKSVVNDKKKEKASV
  MIQNNAYAVAVANYAPNLSKDPVLSTISKSATTPEPNKKPENKPAEAKKTFNSVSKIDRM
  SRIVFPVLFGTFNLVYWATYLNREPVLGVSP

• Sequence length: 451

Pathways

KEGG:

Neuroactive ligand-receptor interaction
Retrograde endocannabinoid signaling
GABAergic synapse
Taste transduction
Morphine addiction
Nicotine addiction

Reactome:

GABA receptor activation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Alcohol dependence	Likely pathogenic; Pathogenic	rs2109351409	RCV002250003	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Developmental and epileptic encephalopathy, 78	Pathogenic; Likely pathogenic	rs2109626303, rs2109351409, rs2475296327, rs2475627246, rs1577800481, rs1281490675, rs1577975808, rs1243977956	RCV002210941 RCV003333212 RCV003883213 RCV004594856 RCV000850101 RCV000850102 RCV000850103 RCV000850104 RCV001254161	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
GABRA2-related disorder	Likely pathogenic	rs2475296302	RCV003427927	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Alcoholism, susceptibility to	risk factor	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANXIETY DISORDERS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISTIC DISORDER	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CANNABIS DEPENDENCE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CANNABIS USE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CENTRAL NERVOUS SYSTEM CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental and epileptic encephalopathy	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 78	—	Disgenet, HPO Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPILEPSY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GENERALISED EPILEPSY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOBLASTOMA MULTIFORME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
JUVENILE MYOCLONIC EPILEPSY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-SPECIFIC EARLY-ONSET EPILEPTIC ENCEPHALOPATHY	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARTIAL EPILEPSY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SUBSTANCE ABUSE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 1 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UNDETERMINED EARLY-ONSET EPILEPTIC ENCEPHALOPATHY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UTERINE FIBROID	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer`s Disease	Alzheimer disease	GWASCAT_DG	26830138		★☆☆☆☆ Found in Text Mining only
Antisocial Personality Disorder	Antisocial Personality Disorder	BEFREE	19783384		★☆☆☆☆ Found in Text Mining only
Antisocial Personality Disorder	Antisocial personality disorder	Pubtator	19783384, 31790348	Associate	★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	16874763, 30087324		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety disorder	Pubtator	16874763	Associate	★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	16874763, 30087324		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anxiety Disorders	Anxiety Disorder	CTD_human_DG	18313124		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anxiety States, Neurotic	Anxiety Disorder	CTD_human_DG	18313124		★☆☆☆☆ Found in Text Mining only
Astrocytoma	Astrocytoma	Pubtator	37169070	Associate	★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	CTD_human_DG	18821008		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	Pubtator	25124326	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Brain Diseases	Brain disease	Pubtator	32347641	Associate	★☆☆☆☆ Found in Text Mining only
Cholestasis of pregnancy	Cholestasis of pregnancy	BEFREE	23480690		★☆☆☆☆ Found in Text Mining only
Conduct Disorder	Conduct Disorder	BEFREE	16557364, 19783384, 24687270		★☆☆☆☆ Found in Text Mining only
Conduct Disorder	Conduct disorder	Pubtator	19783384	Associate	★☆☆☆☆ Found in Text Mining only
Congenital neurologic anomalies	Drachtman Weinblatt Sitarz syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	29961870	Associate	★☆☆☆☆ Found in Text Mining only
Disruptive Impulse Control and Conduct Disorders	Disruptive, impulse control, and conduct disorders	Pubtator	22882390, 23561058	Associate	★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	33350104	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	29046322, 29947131, 29961870		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epilepsy	Epilepsy	Pubtator	29947131, 29961870	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epilepsy, Generalized	Epilepsy	GWASCAT_DG	30531953		★☆☆☆☆ Found in Text Mining only
Epilepsy, Temporal Lobe	Epilepsy	BEFREE	21071388		★☆☆☆☆ Found in Text Mining only
Epileptic encephalopathy	Epileptic encephalopathy	BEFREE	29422393		★☆☆☆☆ Found in Text Mining only
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2	Epileptic encephalopathy	BEFREE	27768696		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	29961870		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	GENOMICS_ENGLAND_DG	678219		★☆☆☆☆ Found in Text Mining only
Huntington Disease	Huntington Disease	BEFREE	27033668		★☆☆☆☆ Found in Text Mining only
Infantile Severe Myoclonic Epilepsy	Myoclonic Epilepsy	BEFREE	27768696		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	678219		★☆☆☆☆ Found in Text Mining only
Intrahepatic Cholestasis of Pregnancy	Intrahepatic cholestasis of pregnancy	Pubtator	23480690	Associate	★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	BEFREE	29422393		★☆☆☆☆ Found in Text Mining only
Nervous System Diseases	Nervous system disease	Pubtator	25124326	Associate	★☆☆☆☆ Found in Text Mining only
Non-specific early-onset epileptic encephalopathy	Non-Specifi Epileptic Encephalopathy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obesity	Obesity	BEFREE	20716301, 25514066		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	20716301	Associate	★☆☆☆☆ Found in Text Mining only
Pruritus	Pruritus	Pubtator	23480690	Associate	★☆☆☆☆ Found in Text Mining only
Seasonal Affective Disorder	Seasonal Affective Disorder	BEFREE	30138693		★☆☆☆☆ Found in Text Mining only
Spasms Infantile	Infantile spasms	Pubtator	35830182	Associate	★☆☆☆☆ Found in Text Mining only
Status Epilepticus	Status epilepticus	Pubtator	24613745	Associate	★☆☆☆☆ Found in Text Mining only