GABRA2

Summary

GABRA2 (gamma-aminobutyric acid type A receptor subunit alpha2, HGNC:4076) is a protein-coding gene on chromosome 4p12, encoding Gamma-aminobutyric acid receptor subunit alpha-2 (P47869). Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

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 different isoforms have been found for this gene.

Source: NCBI Gene 2555 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 78 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 383 total — 6 pathogenic, 11 likely-pathogenic (top 9% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈21% of expected missense variation)
• GTEx eGene: eQTL in 25 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 62
• Drug target: yes — 3 curated mechanism-of-action drugs, 1 via a complex or family; 46 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 1 — Bromazepam
• Approved drugs acting on a complex or family including it: 1 — Zopiclone (GABA-A receptor; agonist GABA site)
• Constraint (gnomAD): pLI 0.98 (loss-of-function intolerant), LOEUF 0.49 (moderately constrained)
• MANE Select transcript: NM_000807

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4076
Approved symbol	GABRA2
Name	gamma-aminobutyric acid type A receptor subunit alpha2
Location	4p12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000151834
Ensembl biotype	protein_coding
OMIM	137140
Entrez	2555

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 22 protein_coding, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000381620

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 2, TSL 3: 4, TSL 4: 1, TSL 5: 6

ENST00000381620, ENST00000356504, ENST00000503806, ENST00000506961, ENST00000507069, ENST00000507460, ENST00000509716, ENST00000510233, ENST00000510861, ENST00000513005, ENST00000514090, ENST00000514193, ENST00000514236, ENST00000515082, ENST00000540012, ENST00000630416, ENST00000863563, ENST00000863564, ENST00000863565, ENST00000863566, ENST00000863567, ENST00000863568, ENST00000960092, ENST00000960093, ENST00000960094, ENST00001001269, ENST00001001270, ENST00001001271, ENST00001113755

RefSeq mRNA: 16 — MANE Select: NM_000807 NM_000807, NM_001114175, NM_001286827, NM_001330690, NM_001377144, NM_001377145, NM_001377146, NM_001377147, NM_001377148, NM_001377149, NM_001377150, NM_001377151, NM_001377152, NM_001377153, NM_001377154, NM_001377155

CCDS: CCDS3471, CCDS82921, CCDS93494

Canonical transcript exons

ENST00000381620 — 10 exons

Exon	Start	End
ENSE00001002000	46332615	46332682
ENSE00001002004	46305568	46305711
ENSE00001489263	46389735	46390128
ENSE00003458320	46310173	46310255
ENSE00003494083	46386074	46386189
ENSE00003496336	46312496	46312716
ENSE00003531854	46303460	46303612
ENSE00003558735	46388636	46388716
ENSE00003654430	46261926	46262128
ENSE00004797456	46243548	46250604

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 97.67.

FANTOM5 (CAGE): breadth broad, TPM avg 9.0228 / max 674.6199, expressed in 289 samples.

Highest expression (Bgee): frontal pole, entorhinal cortex, postcentral gyrus, Brodmann (1909) area 23, superior frontal gyrus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GABRA2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 25 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	1.1e-26	+0.52	4:46485734:C:T
Testis	eqtl	5.6e-18	-0.67	4:46389039:C:CAT
Artery Tibial	eqtl	1.9e-12	+0.62	4:46446448:G:A
Esophagus Muscularis	eqtl	5.2e-10	+0.49	4:46446448:G:A
Adipose Subcutaneous	eqtl	2.7e-08	+0.27	4:45942467:T:C
Thyroid	eqtl	1.2e-07	+0.48	4:46504957:G:A
Small Intestine Terminal Ileum	eqtl	4.3e-07	-0.41	4:46389556:T:A
Esophagus Gastroesophageal Junction	eqtl	3.3e-05	+0.28	4:46336131:A:G
Brain Nucleus accumbens basal ganglia	eqtl	1.5e-04	+0.21	4:46297753:G:A
Esophagus Mucosa	eqtl	3.0e-04	+0.37	4:46446448:G:A
Colon Sigmoid	eqtl	3.8e-04	+0.31	4:46254695:T:C
Colon Transverse	eqtl	4.1e-04	+0.43	4:46576007:C:T
Adipose Visceral Omentum	eqtl	7.6e-04	+0.42	4:46446448:G:A
Brain Cortex	eqtl	8.4e-04	+0.16	4:46333638:A:C
Stomach	eqtl	1.2e-03	+0.35	4:46446448:G:A
Skin Sun Exposed Lower leg	eqtl	3.2e-03	+0.33	4:46446448:G:A
Artery Aorta	eqtl	3.4e-03	-0.48	4:46371211:T:C
Breast Mammary Tissue	eqtl	7.4e-03	-0.57	4:46324306:G:A
Brain Anterior cingulate cortex BA24	eqtl	8.0e-03	-0.32	4:45601262:G:T
Lung	eqtl	1.5e-02	-0.36	4:45483078:C:T

FANTOM5 promoters

showing 10 of 17 alternative TSS:

Promoter ID	TPM avg	Samples expressed
52014	4.9164	235
52017	1.7169	174
52008	0.6434	101
52013	0.3717	92
52015	0.2425	77
52012	0.2179	77
52016	0.2018	71
52010	0.1894	59
52005	0.1356	47
52019	0.0848	47

Top tissues by expression

showing 100 of 284 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	97.67	gold quality
entorhinal cortex	UBERON:0002728	95.91	gold quality
postcentral gyrus	UBERON:0002581	94.76	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.24	gold quality
superior frontal gyrus	UBERON:0002661	94.22	gold quality
parietal lobe	UBERON:0001872	94.00	gold quality
middle temporal gyrus	UBERON:0002771	93.72	gold quality
occipital lobe	UBERON:0002021	92.95	gold quality
primary visual cortex	UBERON:0002436	92.94	gold quality
temporal lobe	UBERON:0001871	92.61	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.48	gold quality
caudate nucleus	UBERON:0001873	91.92	gold quality
lateral globus pallidus	UBERON:0002476	91.83	gold quality
nucleus accumbens	UBERON:0001882	91.38	gold quality
orbitofrontal cortex	UBERON:0004167	90.94	gold quality
putamen	UBERON:0001874	90.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.70	gold quality
frontal cortex	UBERON:0001870	90.67	gold quality
amygdala	UBERON:0001876	90.65	gold quality
prefrontal cortex	UBERON:0000451	90.64	gold quality
telencephalon	UBERON:0001893	90.55	gold quality
neocortex	UBERON:0001950	90.45	gold quality
cerebral cortex	UBERON:0000956	90.30	gold quality
paraflocculus	UBERON:0005351	90.30	gold quality
cortical plate	UBERON:0005343	90.06	gold quality
cingulate cortex	UBERON:0003027	89.65	gold quality
anterior cingulate cortex	UBERON:0009835	89.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.15	gold quality
right frontal lobe	UBERON:0002810	88.34	gold quality
Ammon’s horn	UBERON:0001954	88.12	gold quality
Brodmann (1909) area 10	UBERON:0013541	87.38	gold quality
forebrain	UBERON:0001890	85.99	gold quality
middle frontal gyrus	UBERON:0002702	85.49	gold quality
buccal mucosa cell	CL:0002336	84.51	gold quality
brain	UBERON:0000955	84.08	gold quality
dorsal root ganglion	UBERON:0000044	83.55	gold quality
central nervous system	UBERON:0001017	83.52	gold quality
ventricular zone	UBERON:0003053	81.79	gold quality
hypothalamus	UBERON:0001898	80.96	gold quality
corpus callosum	UBERON:0002336	80.87	gold quality
CA1 field of hippocampus	UBERON:0003881	80.51	gold quality
corpus epididymis	UBERON:0004359	80.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.93	gold quality
ganglionic eminence	UBERON:0004023	79.86	gold quality
globus pallidus	UBERON:0001875	79.32	gold quality
endothelial cell	CL:0000115	79.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.15	gold quality
medial globus pallidus	UBERON:0002477	78.13	gold quality
trigeminal ganglion	UBERON:0001675	77.52	gold quality
cerebellum	UBERON:0002037	76.79	gold quality
superior vestibular nucleus	UBERON:0007227	76.26	gold quality
cerebellar cortex	UBERON:0002129	75.88	gold quality
cerebellar hemisphere	UBERON:0002245	75.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.85	gold quality
colonic epithelium	UBERON:0000397	74.24	gold quality
lateral nuclear group of thalamus	UBERON:0002736	73.58	gold quality
cerebellar vermis	UBERON:0004720	73.01	gold quality
substantia nigra pars reticulata	UBERON:0001966	71.16	gold quality
substantia nigra	UBERON:0002038	70.55	gold quality
midbrain	UBERON:0001891	69.90	gold quality
ventral tegmental area	UBERON:0002691	69.53	gold quality
rectum	UBERON:0001052	69.15	gold quality
tibial nerve	UBERON:0001323	68.26	gold quality
pons	UBERON:0000988	67.88	gold quality
embryo	UBERON:0000922	67.68	gold quality
dorsal plus ventral thalamus	UBERON:0001897	67.60	gold quality
sural nerve	UBERON:0015488	67.50	gold quality
medulla oblongata	UBERON:0001896	67.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	66.51	gold quality
metanephros cortex	UBERON:0010533	66.43	gold quality
substantia nigra pars compacta	UBERON:0001965	66.39	gold quality
adult mammalian kidney	UBERON:0000082	66.25	gold quality
spinal cord	UBERON:0002240	66.06	gold quality
adult organism	UBERON:0007023	65.32	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.03	gold quality
islet of Langerhans	UBERON:0000006	64.10	gold quality
kidney	UBERON:0002113	63.83	gold quality
transverse colon	UBERON:0001157	63.72	gold quality
small intestine	UBERON:0002108	63.50	gold quality
calcaneal tendon	UBERON:0003701	63.10	gold quality
colon	UBERON:0001155	62.78	gold quality
intestine	UBERON:0000160	62.74	gold quality
muscle layer of sigmoid colon	UBERON:0035805	62.73	gold quality
renal medulla	UBERON:0000362	62.46	gold quality
inferior vagus X ganglion	UBERON:0005363	62.45	gold quality
large intestine	UBERON:0000059	62.38	gold quality
subthalamic nucleus	UBERON:0001906	62.02	gold quality
sigmoid colon	UBERON:0001159	61.84	gold quality
metanephros	UBERON:0000081	60.99	gold quality
germinal epithelium of ovary	UBERON:0001304	60.84	gold quality
gall bladder	UBERON:0002110	59.41	gold quality
kidney epithelium	UBERON:0004819	59.03	silver quality
cortex of kidney	UBERON:0001225	59.02	gold quality
renal glomerulus	UBERON:0000074	58.98	silver quality
colonic mucosa	UBERON:0000317	58.81	gold quality
metanephric glomerulus	UBERON:0004736	58.70	silver quality
subcutaneous adipose tissue	UBERON:0002190	57.82	gold quality
mucosa of sigmoid colon	UBERON:0004993	57.18	silver quality
decidua	UBERON:0002450	56.91	gold quality
mucosa of stomach	UBERON:0001199	56.21	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	19.95
E-GEOD-84465	yes	12.61
E-GEOD-137537	yes	7.10
E-ANND-3	yes	5.63

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 70 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Hippocampal formation	tissue	171.0
Entorhinal cortex	tissue	114.0
Putamen	tissue	113.1
Cerebral cortex	tissue	112.1
Temporal cortex	tissue	112.1
Prefrontal cortex	tissue	110.4
Occipital cortex	tissue	105.3
Basal ganglia	tissue	103.6
Somatosensory cortex	tissue	103.6
Motor cortex	tissue	103.1
Retrosplenial and cingulate cortex	tissue	98.7
Postcentral gyrus	tissue	92.0
Amygdala	tissue	91.8
Insular cortex	tissue	91.6
Ventral forebrain	tissue	90.8
Retrosplenial cortex	tissue	87.1
Septum	tissue	86.5
Thalamus	tissue	81.9
Hippocampus	tissue	74.8
Nucleus accumbens	tissue	74.5
Midbrain	tissue	66.0
Spinal cord	tissue	64.7
Pons	tissue	59.6
Hypothalamus	tissue	57.9
Superior colliculi	tissue	56.0
Caudate putamen	tissue	54.2
Olfactory bulb	tissue	52.8
Medulla oblongata	tissue	50.5
Periaqueductal gray	tissue	46.1
Frontal cortex	tissue	42.8
Substantia nigra	tissue	35.1
Corpus callosum	tissue	28.6
Cerebellum	tissue	24.1
Locus coeruleus	tissue	19.4
Epididymis	tissue	8.3
Kidney	tissue	5.9
Small intestine	tissue	5.6
Choroid plexus	tissue	5.5
Colon	tissue	2.8
Retina	tissue	2.2
Rectum	tissue	2.0
Adipose tissue	tissue	1.1
Spleen	tissue	1.1
Duodenum	tissue	0.8
Breast	tissue	0.7
Seminal vesicle	tissue	0.7
Esophagus	tissue	0.7
Vagina	tissue	0.6
Cervix	tissue	0.5
Stomach 1	tissue	0.5
Gallbladder	tissue	0.5
Testis	tissue	0.4
Ovary	tissue	0.4
Endometrium 1	tissue	0.4
Placenta	tissue	0.4
Thymus	tissue	0.4
Tonsil	tissue	0.4
Appendix	tissue	0.4
Pituitary gland	tissue	0.3
Lymph node	tissue	0.3

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Dorsal hippocampus (171.0), Ventral hippocampus (140.3), Subiculum (111.5), Temporal pole (96.5), Hippocampus, CA1 (92.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting GABRA2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 65 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-409-3P	99.50	66.33	1192

Functional genomics

gnomAD constraint: pLI 0.984, LOEUF 0.49, missense Z 3.41 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000381620 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈21% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
4:46,250,311–46,261,945	99 / 124.3	0.80	no
4:46,261,946–46,303,567	24 / 113.8	0.21	yes (p 3.9e-17)
4:46,303,568–46,386,149	113 / 257.1	0.44	no
4:46,386,150–46,388,706	39 / 40.5	0.96	no

Literature-anchored findings (GeneRIF, showing 40)

• GABRA2 might influence susceptibility to alcohol dependence by modulating the level of neural excitation (PMID:15024690)
• extracellular domain models show subunit arrangement of GABA-A receptors (PMID:15033447)
• A complex pattern of alternative splicing and alternative promoter use of the human GABRA2 mRNA was demonstrated. There are four major isoforms consisting of combinations of two alternative 5’ and 3’ exons. (PMID:15950776)
• Risk for alcohol dependence associated with GABRA2 is not evident until the mid-20s and then remains throughout adulthood, which is also associated with other drug dependence. (PMID:16557364)
• Results suggest an association between marijuana dependence, illicit drug dependence and alcoholism with single nucleotide polymorphismss in the GABRA2 gene. (PMID:16622805)
• A modest associations between GABRA2 genotypes and addiction phenotypes. (PMID:16894595)
• gabra2 gene is associated with risk for alcohol dependence. (PMID:17207817)
• The GABRA2 haplotype block may act in a dominant manner in relation to risk of alcohol dependence. (PMID:17507911)
• no evidence of a relationship between GABRA2 and alcohol dependence (PMID:17690794)
• The assessment of genetic vulnerability may be relevant to studies of the efficacy of psychosocial treatment: GABRA2 genotype modifies the variance in drinking and can therefore moderate power for resolving differences between treatments. (PMID:17949392)
• study of patterns of htSNPs & linkage disequilibrium (LD)in 6 populations; LD extended from most of the GABRA2 gene through the GABRG1 locus in the same GABAA cluster region suggesting possible association of these genes with alcohol dependence (PMID:17976953)
• GABRA2 mRNA levels significantly differed by GABRA2 genotype. GABRA2 single nucleotide polymorphisms were associated with sensitivity to the acute effects of alcohol. (PMID:18005236)
• GABRA2 variation contributes to genetic susceptibility to alcohol dependence. Allelic associations were found for body sway, motor coordination, pursuit rotor and arithmetical computation tasks and neuroticism. (PMID:18361719)
• Genes such as ELTD1 on chromosome 1, in addition to genes on chromosomes 4 (eg, GABRA2) and 6 (eg, CNR1), may be associated with the genetic risk for cannabis use disorders. (PMID:18519829)
• GABRA2 allelic associations found in clinical case-control studies have detectable but minor effects on DSM-defined alcohol dependence in the general community. (PMID:18727688)
• results demonstrated that GABRA2–originally associated with a diagnosis of alcohol dependence in adults–also predicted the onset of symptoms among subjects in their 20s (PMID:18781239)
• results suggest that there are likely to be independent, complex contributions from both GABRG1 and GABRA2 to alcoholism vulnerability based on the genotyping of 24 GABRG1 and GABRA2 SNPs in Finnish Caucasian men and Plains Indian men and women. (PMID:18818659)
• Data show that GABRA2 is significant reductions in parietal cortex in subjects with autism. (PMID:18821008)
• Of the 39 newly genotyped SNPs, 19 SNPs were associated with case status (FTND scores of 4+) at P-values less than 0.01. (PMID:19207358)
• examined whether risk for PTSD is associated with G x E interactions involving GABRA2 polymophism and childhood trauma exposure (PMID:19229201)
• The GABRA2 gene was associated with class membership, with subjects who showed persistent elevated trajectories of externalizing behavior more likely to carry the genotype previously associated with increased risk of adult alcohol dependence. (PMID:19487630)
• Genetic variation at or near the GABRA2 locus significantly affects vulnerability not only to alcohol dependence, but to other forms of substance use including nicotine dependence and cannabis dependence, and that the effects may be sex dependent. (PMID:19672139)
• No association between GABRA2 single nucleotide polymorphism and alcohol dependence in adolescents. (PMID:19783384)
• Together with childhood trauma, GABRA2 variation influences risk and resilience for all addiction but most strongly for heroin dependence. (PMID:19833324)
• These findings suggest that common variation in the GABRA2, GABRA3, GABRA6, and GABRG2 genes does not play a major role in liability to anxiety spectrum disorders. (PMID:19842164)
• In stroke case, the GABRA2 was down regulation in auditory cortex. (PMID:20048764)
• No evidence of an association is found at the allele, genotype, haplotype, or diplotype levels between the alpha-2 subunit of GABA receptor single nucleotide polymorphisms and alcoholism in Italian controls. (PMID:20102561)
• found specific markers and haplotypes of the GABRA2 gene to be associated with cocaine addiction (PMID:20133874)
• Study propose that the collybistin-gephyrin complex has an intimate role in the clustering of GABA(A)Rs containing the alpha2 subunit. (PMID:20622020)
• These are the first data to suggest that GABRA2 genotype could affect the brain’s responses to cues associated with alcohol. (PMID:20698837)
• conduct problems, and a conduct-problem-associated GABRA2 genotype, decrease the age-of-onset and/or increase the lifetime duration of obesity. (PMID:20716301)
• In subjects with schizophrenia, mean GABA(A) alpha2 receptor subunit mRNA expression is 14% higher in layer 2 of the dorsolateral prefrontal cortex. (PMID:20843900)
• 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. (PMID:21118274)
• results suggest that GABRA2 genetic variation is associated with Impulsiveness through variation of insula activity responses. (PMID:21483437)
• no evidence for an association between GABRA2 polymorphisms and alcohol dependence. (PMID:21683760)
• 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. (PMID:21751815)
• a highly significant difference was shown between alcohol dependence subjects and controls in the frequency of a single nucleotide polymorphisms GABRA2 haplotype (PMID:21919924)
• 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. (PMID:22047728)
• GABRA2 genotype, as well as the number of intake drug abuse problems and a younger age, were associated with an increased risk of relapse (PMID:22129841)
• Variation within GABRA2 is associated with attenuated negative responses to alcohol, a known risk factor for vulnerability to alcohol use disorders. (PMID:22501025)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabra2b	ENSDARG00000113737
mus_musculus	Gabra2	ENSMUSG00000000560
rattus_norvegicus	Gabra2	ENSRNOG00000002349

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090), GABRA5 (ENSG00000186297), ZACN (ENSG00000186919), GABRD (ENSG00000187730), CHRNG (ENSG00000196811), GABRQ (ENSG00000268089)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95614) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 27 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal GABA-mediated receptor currents	2
impaired behavioral response to xenobiotic	2
cornea opacity	1
increased anxiety-related response	1
hyperactivity	1
decreased locomotor activity	1
decreased exploration in new environment	1
trunk curl	1
limb grasping	1
decreased chemically-elicited antinociception	1
postnatal lethality	1
abnormal CNS synaptic transmission	1
increased thigmotaxis	1
abnormal conditioned emotional response	1
increased lean body mass	1
abnormal behavior	1
decreased heart rate	1
decreased survivor rate	1
decreased physiological sensitivity to xenobiotic	1
abnormal miniature inhibitory postsynaptic currents	1
enhanced contextual conditioning behavior	1
enhanced cued conditioning behavior	1
enhanced behavioral response to anesthetic	1
decreased total body fat amount	1
prolonged RR interval	1

+2 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca mulatta	D1LYT2	100.0%	Diamond
Drosophila melanogaster	P25123	99.8%	Diamond
Bos taurus	P57695	99.8%	Diamond
Macaca fascicularis	Q4R534	99.8%	Diamond
Pongo abelii	Q5RCC5	99.8%	Diamond
Drosophila simulans	Q9BLY8	99.8%	Diamond
Gallus gallus	P19150	96.9%	Diamond
Musca domestica	Q75NA5	84.3%	Diamond
Haemonchus contortus	P91730	81.4%	Diamond
Caenorhabditis elegans	Q17328	81.4%	Diamond
Lymnaea stagnalis	P26714	58.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GABRG1	protein-coding	2565
COX7B2	protein-coding	170712
GABRA4	protein-coding	2557

Protein

Protein identifiers

Gamma-aminobutyric acid receptor subunit alpha-2 — P47869 (reviewed: P47869)

Alternative names: GABA(A) receptor subunit alpha-2

All UniProt accessions (10): P47869, A0A0A0MTM5, D6RAA9, D6RB77, D6RBK9, D6RBL7, D6RCS5, E9PBQ7, G5E9Z6, H0Y9V8

UniProt curated annotations — full annotation on UniProt →

Function. Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain. GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interfaces. When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission. The alpha-2 subunit exhibits synaptogenic activity together with beta-2 and very little to no activity together with beta-3, the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation.

Subunit / interactions. Heteropentamer, formed by a combination of alpha (GABRA1-6), beta (GABRB1-3), gamma (GABRG1-3), delta (GABRD), epsilon (GABRE), rho (GABRR1-3), pi (GABRP) and theta (GABRQ) subunits, each subunit exhibiting distinct physiological and pharmacological properties. Interacts with UBQLN1. Interacts with KIF21B. Interacts with LHFPL4. Interacts with SHISA7; interaction leads to the regulation of GABA(A) receptor trafficking, channel deactivation kinetics and pharmacology.

Subcellular location. Postsynaptic cell membrane. Cell membrane. Cytoplasmic vesicle membrane. Cell projection. Dendrite.

Post-translational modifications. Glycosylated.

Disease relevance. Developmental and epileptic encephalopathy 78 (DEE78) [MIM:618557] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE78 is an autosomal dominant form characterized by onset of refractory seizures in the first days or months of life. Clinical features include severe developmental delay, hypotonia, microcephaly, cortical visual impairment and profound intellectual disability. Some patients manifest a less severe phenotype characterized by pharmacoresponsive epilepsy, autism spectrum disorder and moderate intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by pentobarbital. Inhibited by the antagonist bicuculline.

Domain organisation. The extracellular domain contributes to synaptic contact formation. The GABA-binding pockets are located at the interface between neighboring alpha and beta subunits. GABAARs subunits share a common topological structure: a peptide sequence made up of a long extracellular N-terminal, four transmembrane domains, intracellular or cytoplasmic domain located between the third and the fourth transmembrane domains.

Polymorphism. Genetic variations in GABRA2 determine the genetic susceptibility to alcoholism [MIM:103780].

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA2 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P47869-1	1	yes
P47869-2	2

RefSeq proteins (16): NP_000798, NP_001107647, NP_001273756, NP_001317619, NP_001364073, NP_001364074, NP_001364075, NP_001364076, NP_001364077, NP_001364078, NP_001364079, NP_001364080, NP_001364081, NP_001364082, NP_001364083, NP_001364084 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001390	GABAAa_rcpt	Family
IPR005432	GABBAa2_rcpt	Family
IPR006028	GABAA/Glycine_rcpt	Family
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR018000	Neurotransmitter_ion_chnl_CS	Conserved_site
IPR036719	Neuro-gated_channel_TM_sf	Homologous_superfamily
IPR036734	Neur_chan_lig-bd_sf	Homologous_superfamily
IPR038050	Neuro_actylchol_rec	Homologous_superfamily
IPR047023	Gabra-2_ECD	Domain
IPR047024	Gabra-1-6_TM	Domain

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea)

• chloride(in) = chloride(out) (RHEA:29823)

UniProt features (57 total): strand 15, helix 11, sequence variant 7, topological domain 5, turn 4, transmembrane region 4, binding site 2, glycosylation site 2, splice variant 2, sequence conflict 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

15 structures by resolution:

PDB	Title	Method	Resolution (Å)
9QJS	GABA-A receptor a2b3 (1:4) + a2NB16(silent) + b3Mb125 + GABA	ELECTRON MICROSCOPY	2.52
9QJX	GABA-A receptor a2b3g2 + a2NB00(PAM) + GABA	ELECTRON MICROSCOPY	2.7
9QJY	GABA-A receptor a2b3g2 + a2NB04(silent) + GABA	ELECTRON MICROSCOPY	2.78
9QJR	GABA-A receptor a2b3 (1:4) + a2NB29(near-silent) + b3Mb125 + GABA	ELECTRON MICROSCOPY	2.92
9QK0	GABA-A receptor a2b3g2 + a2NB25(inhibitor)	ELECTRON MICROSCOPY	3.01
9QK1	GABA-A receptor a2b3 (1:4) + a2NB06(silent) + b3Mb125 + GABA	ELECTRON MICROSCOPY	3.05
9CRV	Native human GABAA receptor of beta2-alpha1-gamma2-beta2-alpha2 assembly	ELECTRON MICROSCOPY	3.18
9CT0	Native human GABAA receptor of beta2-alpha1-beta2-alpha2-gamma2 assembly	ELECTRON MICROSCOPY	3.19
9CX7	Native human GABAA receptor of beta3-alpha1-gamma2-beta3-alpha2 assembly	ELECTRON MICROSCOPY	3.3
9CXC	Native human GABAA receptor of beta3-alpha1-gamma2-beta2-alpha2 assembly	ELECTRON MICROSCOPY	3.3
9CXB	Native human GABAA receptor of beta2-alpha1-beta1-alpha2-gamma2 assembly	ELECTRON MICROSCOPY	3.33
9CSB	Native human GABAA receptor of beta3-alpha1-beta2-alpha2-gamma2 assembly	ELECTRON MICROSCOPY	3.34
9CTV	Native human GABAA receptor of beta2-alpha1-gamma2-beta1-alpha2 assembly	ELECTRON MICROSCOPY	3.36
9QJV	GABA-A receptor a2b3 (1:4) + a2NB47(silent) + b3Mb125 + GABA	ELECTRON MICROSCOPY	3.45
9CTJ	Native human GABAA receptor of beta2-alpha1-beta3-alpha2-gamma2 assembly	ELECTRON MICROSCOPY	3.74

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P47869-F1	83.71	0.62

Antibody-complex structures (SAbDab)

7 antibodies co-crystallized with this protein: 9CRV, 9CT0, 9CTJ, 9CTV, 9CX7, 9CXB, 9CXC

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Epilepsy, Mental and behavioural disorders

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; nucleoplasm

Antibody reliability (HPA): IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2)

Position	Role
94	4-aminobutanoate
157	4-aminobutanoate

Disulfide bonds (1)

Type	Positions
Disulfide bond	166–180

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	38, 138

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-977443	GABA receptor activation	electronic
R-HSA-112316	Neuronal System	—
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission	—
R-HSA-112315	Transmission across Chemical Synapses	—

MSigDB gene sets: 283 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_SYNAPSE_ASSEMBLY, MODULE_563, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, MODULE_503, GOBP_CELL_CELL_SIGNALING, ATGTTAA_MIR302C, chr4p12, GOBP_CELL_JUNCTION_ORGANIZATION, MODULE_289, MODULE_195, GOBP_CHLORIDE_TRANSPORT

GO Biological Process (9): gamma-aminobutyric acid signaling pathway (GO:0007214), synaptic transmission, GABAergic (GO:0051932), chloride transmembrane transport (GO:1902476), inhibitory synapse assembly (GO:1904862), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220), regulation of postsynaptic membrane potential (GO:0060078), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (11): GABA-A receptor activity (GO:0004890), benzodiazepine receptor activity (GO:0008503), GABA-gated chloride ion channel activity (GO:0022851), ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential (GO:0099507), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), chloride channel activity (GO:0005254), protein binding (GO:0005515), signaling receptor activity (GO:0038023)

GO Cellular Component (16): plasma membrane (GO:0005886), axon (GO:0030424), synaptic vesicle membrane (GO:0030672), dendrite membrane (GO:0032590), chloride channel complex (GO:0034707), neuronal cell body (GO:0043025), inhibitory synapse (GO:0060077), postsynapse (GO:0098794), GABA-ergic synapse (GO:0098982), postsynaptic specialization membrane (GO:0099634), GABA-A receptor complex (GO:1902711), membrane (GO:0016020), dendrite (GO:0030425), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), postsynaptic membrane (GO:0045211)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Neurotransmitter receptors and postsynaptic signal transmission	1
Transmission across Chemical Synapses	1
Neuronal System	1

GO top-level categories

49 GO namespaces:

Category	Terms
synapse	3
GABA receptor activity	2
regulation of membrane potential	2
transmitter-gated monoatomic ion channel activity	2
ligand-gated monoatomic ion channel activity	2
neuron projection	2
cellular anatomical structure	2
synaptic membrane	2
cell-cell signaling	1
chemical synaptic transmission	1
chloride transport	1
monoatomic anion transmembrane transport	1
synapse assembly	1
transport	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
neurotransmitter receptor activity	1
chloride channel activity	1
ligand-gated monoatomic anion channel activity	1
presynaptic membrane	1
regulation of presynaptic membrane potential	1
regulation of postsynaptic membrane potential	1
signaling receptor activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
binding	1
molecular transducer activity	1
membrane	1
cell periphery	1
synaptic vesicle	1
exocytic vesicle membrane	1
dendrite	1
neuron projection membrane	1
monoatomic ion channel complex	1
somatodendritic compartment	1
cell body	1
postsynaptic membrane	1
postsynaptic specialization	1
GABA receptor complex	1
dendritic tree	1
vesicle membrane	1
cytoplasmic vesicle	1
cytoplasm	1
intracellular vesicle	1
postsynapse	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 36 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
chloride transmembrane transport	BP	direct assay
gamma-aminobutyric acid signaling pathway	BP	mutant phenotype
GABA-A receptor complex	CC	direct assay
synaptic vesicle membrane	CC	direct assay
GABA-gated chloride ion channel activity	MF	direct assay
benzodiazepine receptor activity	MF	mutant phenotype
ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	MF	direct assay
transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,192 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRA2	CHRM2	P08172	666
GABRA2	DRD2	P14416	582
GABRA2	OPRM1	P35372	562
GABRA2	PGM1	P36871	552
GABRA2	SLC6A4	P31645	550
GABRA2	ANKK1	Q8NFD2	548
GABRA2	ADH1B	P00325	547
GABRA2	GABBR2	O75899	523
GABRA2	SLC6A1	P30531	515
GABRA2	DRD4	P21917	513
GABRA2	COMT	P21964	503
GABRA2	GRIA3	P42263	501
GABRA2	SCN1A	P35498	485
GABRA2	GAD1	Q99259	481
GABRA2	GRIN2A	Q12879	480

IntAct

Human interaction partners of GABRA2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
EGFR	physical association	0.500	1
E7	physical association	0.370	1
MDM2	physical association	0.000	1

BioGRID (8 interactions; top human partners by supporting records): EGFR (Affinity Capture-Western; 2 records), CSK (Synthetic Lethality), GABRG2 (FRET), UBQLN1 (Two-hybrid)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
GABRA2	“form complex”	“GABA-A (a2-b1-g2) receptor”	binding
PCDH19	“up-regulates quantity by stabilization”	GABRA2	binding

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
GABRA2;GABRB3;GABRG2		Signaling by GABA

Disease & clinical

Genetic variants

Variant evidence for GABRA2: 383 ClinVar records (17 pathogenic / likely pathogenic); 2 PharmGKB clinical annotations; 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

383 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	11
Uncertain significance	161
Likely benign	161
Benign	16

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 17 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
3338107	NM_000807.4(GABRA2):c.988_989insTTATG (p.Glu330fs)	Pathogenic	criteria provided, single submitter	1
4526429	NM_000807.4(GABRA2):c.895A>C (p.Ser299Arg)	Pathogenic	criteria provided, single submitter	1
689387	NM_000807.4(GABRA2):c.875C>A (p.Thr292Lys)	Likely pathogenic	criteria provided, single submitter	2
976773	NM_000807.4(GABRA2):c.875C>T (p.Thr292Ile)	Likely pathogenic	criteria provided, single submitter	1
1919477	NM_000807.4(GABRA2):c.850G>A (p.Val284Met)	Likely pathogenic	criteria provided, single submitter	1
2635567	NM_000807.4(GABRA2):c.883A>T (p.Thr295Ser)	Likely pathogenic	criteria provided, single submitter	1
2718827	NM_000807.4(GABRA2):c.124T>A (p.Phe42Ile)	Likely pathogenic	criteria provided, single submitter	1
3338106	NM_000807.4(GABRA2):c.644T>C (p.Leu215Ser)	Likely pathogenic	criteria provided, single submitter	1
3338108	NM_000807.4(GABRA2):c.460C>G (p.Leu154Val)	Likely pathogenic	criteria provided, single submitter	1
3342660	NM_000807.4(GABRA2):c.197C>T (p.Thr66Ile)	Likely pathogenic	criteria provided, single submitter	1
3377080	NM_000807.4(GABRA2):c.850G>T (p.Val284Leu)	Likely pathogenic	criteria provided, single submitter	1
3602196	NM_000807.4(GABRA2):c.281G>A (p.Arg94Gln)	Likely pathogenic	criteria provided, single submitter	1
4074841	NM_000807.4(GABRA2):c.851T>G (p.Val284Gly)	Likely pathogenic	criteria provided, single submitter	1
689388	NM_000807.4(GABRA2):c.871C>G (p.Leu291Val)	Pathogenic	no assertion criteria provided	1
689389	NM_000807.4(GABRA2):c.788T>C (p.Met263Thr)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore GABRA2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 1,140):

Position(s)	Effect	Δscore	Sites
4:46312494–46312495	donor_loss	1.0000	3
4:46312717–46312718	acceptor_loss	1.0000	3
4:46386072–46386073	donor_loss	1.0000	5
4:46386076	donor_gain	1.0000
4:46388273	donor_gain	1.0000
4:46388719	acceptor_gain	1.0000
4:46388728–46388729	acceptor_gain	1.0000	2
4:46388734	acceptor_gain	1.0000
4:46262129–46262130	acceptor_loss	0.9900	6
4:46262301	donor_gain	0.9900

AlphaMissense

1,737 missense substitutions predicted likely pathogenic (of 2,985 scored), across 335 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M293	9	0.968	1.000
M85	9	0.960	0.999
M263	9	0.950	1.000
M168	9	0.940	0.998
M313	9	0.928	0.997
M158	9	0.923	0.992
M139	9	0.867	0.995
D99	8	0.999	1.000
D176	8	0.999	1.000
D314	8	0.999	1.000
D418	8	0.999	1.000
D54	8	0.998	1.000
D125	8	0.998	1.000
H137	8	0.998	1.000
F272	8	0.998	1.000
D90	8	0.996	0.999
F325	8	0.993	0.999
F285	8	0.992	0.998
F425	8	0.992	1.000
F429	8	0.990	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:137140 | disease phenotypes: MIM:618557, MIM:103780

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
developmental and epileptic encephalopathy, 78	Strong	Autosomal dominant	4
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
DDG2P	green
Early onset or syndromic epilepsy	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (4): developmental and epileptic encephalopathy, 78 (MONDO:0032812), alcohol dependence (MONDO:0007079), intellectual disability (MONDO:0001071), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

showing 60 of 62 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000817	Reduced eye contact
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001315	Diminished deep tendon reflex
HP:0001319	Neonatal hypotonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001426	Non-Mendelian inheritance
HP:0001508	Failure to thrive
HP:0001558	Decreased fetal movement
HP:0002020	Gastroesophageal reflux
HP:0002045	Hypothermia
HP:0002059	Cerebral atrophy
HP:0002063	Rigidity
HP:0002072	Chorea
HP:0002133	Status epilepticus
HP:0002317	Unsteady gait
HP:0002376	Developmental regression
HP:0002421	Poor head control
HP:0002509	Limb hypertonia
HP:0002521	Hypsarrhythmia
HP:0002540	Inability to walk
HP:0003429	CNS hypomyelination
HP:0004305	Involuntary movements
HP:0004322	Short stature
HP:0007018	Attention deficit hyperactivity disorder
HP:0010844	EEG with multifocal slow activity
HP:0011344	Severe global developmental delay
HP:0011443	Abnormality of coordination
HP:0011968	Feeding difficulties
HP:0012444	Brain atrophy
HP:0012447	Abnormal myelination
HP:0012547	Abnormal involuntary eye movements
HP:0030955	Addictive alcohol use
HP:0100021	Cerebral palsy
HP:0100660	Dyskinesia

GWAS associations

5 associations:

Study	Trait	p-value
GCST007325_236	General risk tolerance (MTAG)	2e-18
GCST007324_52	Adventurousness	1e-15
GCST006624_63	Systolic blood pressure	3e-11
GCST007353_6	Generalized epilepsy	4e-8
GCST002547_4	Epilepsy	2e-7

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0008579	risk-taking behaviour

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (10): CHEMBL2093872 (PROTEIN COMPLEX GROUP), CHEMBL2094130 (PROTEIN COMPLEX), CHEMBL2109243 (PROTEIN COMPLEX GROUP), CHEMBL2109244 (PROTEIN COMPLEX GROUP), CHEMBL2111413 (PROTEIN COMPLEX), CHEMBL3885571 (PROTEIN COMPLEX), CHEMBL4296064 (PROTEIN COMPLEX), CHEMBL4956 (SINGLE PROTEIN), CHEMBL5291949 (PROTEIN COMPLEX), CHEMBL5303741 (PROTEIN COMPLEX)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the GABRA2 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

3 curated-mechanism drugs:

Drug	Modality	Max phase
BROMAZEPAM	Small molecule	4
AZD7325	Small molecule	2
AZD6280	Small molecule	1

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes GABRA2 — the drug acts on the assembly or class, not necessarily on this subunit alone.

1 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
ZOPICLONE	GABA-A receptor; agonist GABA site	9	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 613,620 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

46 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL661	ALPRAZOLAM	4	131,051
CHEMBL3183409	APALUTAMIDE	4	4,347
CHEMBL3187365	ASENAPINE	4	146
CHEMBL639	AZELASTINE	4	16,951
CHEMBL297302	BENPERIDOL	4	3,436
CHEMBL207538	BREXANOLONE	4	1,647
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,240
CHEMBL515	CHLORAMBUCIL	4	173,945
CHEMBL451	CHLORDIAZEPOXIDE	4	36,835
CHEMBL452	CLONAZEPAM	4	33,611
CHEMBL42	CLOZAPINE	4	37,868
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL12	DIAZEPAM	4	92,923
CHEMBL1082407	ENZALUTAMIDE	4	10,210
CHEMBL1106	EPINASTINE	4	8,600
CHEMBL1522	ESZOPICLONE	4	6,627
CHEMBL681	ETOMIDATE	4	8,520
CHEMBL407	FLUMAZENIL	4	7,208
CHEMBL13280	FLUNITRAZEPAM	4	11,627
CHEMBL1568698	GANAXOLONE	4	1,695
CHEMBL146095	GLAFENINE	4
CHEMBL1544	LIOTHYRONINE	4
CHEMBL448	PENTOBARBITAL	4
CHEMBL526	PROPOFOL	4
CHEMBL1064	SIMVASTATIN	4
CHEMBL222559	TIPRANAVIR	4
CHEMBL646	TRIAZOLAM	4
CHEMBL408	TROGLITAZONE	4
CHEMBL1521	ZALEPLON	4
CHEMBL911	ZOLPIDEM	4
CHEMBL265502	SURAMIN	3
CHEMBL41632	TIRATRICOL	3
CHEMBL1783282	AZD7325	2
CHEMBL454095	ABECARNIL	2
CHEMBL190279	ALFAXALONE	2
CHEMBL8260	BAICALEIN	2
CHEMBL3681419	BASMISANIL	2
CHEMBL366947	BRETAZENIL	2
CHEMBL268254	DELORAZEPAM	2
CHEMBL275638	FLAVONE	2
CHEMBL200177	MK-0777	2
CHEMBL287631	PROGABIDE	2
CHEMBL285802	ZOTEPINE	2
CHEMBL1783256	AZD6280	1
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1
CHEMBL273481	MUSCIMOL	1

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

2 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs11503014	Toxicity	3	cocaine	Cocaine dependence
rs279858	Other	3	sevoflurane

PharmGKB variants

2 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11503014	GABRA2	3	2.00	1	cocaine
rs279858	GABRA2	3	1.00	1	sevoflurane

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

4 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs11503014	propofol	Other	Genotype CC is associated with decreased response to propofol as compared to genotypes CG + GG.	PMID:28611364
rs11503014	cocaine	Toxicity	Allele G is associated with increased severity of Cocaine-Related Disorders due to cocaine as compared to allele C.	PMID:22882391
rs279858	sevoflurane	Other	Genotypes CC + CT are associated with decreased mean arterial pressure when exposed to sevoflurane in people with otorhinolaryngology surgery as compared to genotype TT.	PMID:35943164
rs279847	dexmedetomidine	Toxicity	Genotype GG is associated with decreased heart rate when treated with dexmedetomidine in women as compared to genotypes GT + TT.	PMID:35873555

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: lgic — GABA_A receptors

Most potent curated ligand interactions (11 total), top 11:

Ligand	Action	Affinity	Parameter
CGS8216	Inverse agonist	10.1	pKi
AZD7325	Positive	9.52	pKi
triazolam	Positive	9.23	pKi
flumazenil	Allosteric modulator	9.05	pKi
clonazepam	Positive	8.77	pKi
darigabat	Positive	8.61	pKi
ZK93423	Partial agonist	8.4	pKi
flunitrazepam	Positive	8.28	pKi
alprazolam	Positive	7.92	pEC50
diazepam	Positive	7.77	pKi
zolpidem	Positive	6.12	pKi

Binding affinities (BindingDB)

1283 measured of 1404 human assays (1413 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(4-Ethynyl-phenyl)-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.03 nM
PHENAZEPAM	KI	0.05 nM
8-Ethynyl-2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.06 nM
4-amino-8-[2-fluoro-5-[(4-methoxy-2-pyridinyl)methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.07 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
2-Phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one (CGS 8216)	KI	0.08 nM
8-Bromo-2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.08 nM
CHEMBL5280240	KI	0.1 nM
PW-007A	KI	0.1 nM
4-amino-8-[2-fluoro-5-(pyridin-4-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.12 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
8-Chloro-2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.17 nM
4-amino-8-[5-[(2-cyano-3-pyridinyl)methoxy]-2-fluorophenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.17 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-[2-(1,2,4-triazol-4-yl)ethoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.17 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[5-[(4-cyano-2-pyridinyl)methoxy]-2-fluorophenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.19 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-(pyrimidin-5-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.2 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
2-(4-Bromo-phenyl)-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.21 nM
4-amino-8-(2,6-difluorophenyl)-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.21 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-(pyridazin-3-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.21 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-(6-methoxypyrazin-2-yl)-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.23 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-2-oxo-N-propyl-8-[6-(pyridin-3-ylmethoxy)-2-pyridinyl]-1H-quinoline-3-carboxamide	KI	0.23 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[5-[(5-cyano-2-pyridinyl)methoxy]-2-fluorophenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.24 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
7-cyclobutyl-6-(2-methyl-2H-1,2,4-trizol-3-ylmethoxy)-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine	KI	0.25 nM
4-amino-8-(6-ethoxy-3-fluoro-2-pyridinyl)-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.25 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
CHEMBL3274851	KI	0.26 nM
7-tert-butyl-6-((2-ethyl-2H-1,2,4-triazol-3-yl)methoxy)-3-(2-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine	KI	0.3 nM
4-amino-8-[2-fluoro-5-(pyridin-2-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.3 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-(1,3-oxazol-4-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.3 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-[(5-methyl-1,3,4-oxadiazol-2-yl)methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.3 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
CHEMBL1783282	KI	0.309 nM
4-amino-8-[2-fluoro-5-(1,3-thiazol-4-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.31 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-[(3-methylimidazol-4-yl)methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.37 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
CHEMBL1783284	KI	0.38 nM
4-amino-8-(3-fluoro-6-methoxy-2-pyridinyl)-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.38 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-(pyridin-3-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.39 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
3’-(7-methyl-imidazo[1,2-a]pyrimidin-3-yl)-biphenyl-2-carbonitrile	KI	0.4 nM
6-[[3-(5-chloro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-(oxan-4-yl)pyridazine-3-carboxamide	KI	0.4 nM	US-20240279218: ISOXAZOLYL ETHER DERIVATIVES AS GABA A ALPHA5 PAM
4-amino-8-(2-amino-5-fluoropyrimidin-4-yl)-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.4 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
CHEMBL1783283	KI	0.407 nM
4-amino-8-[2-fluoro-5-(pyridazin-4-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.41 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-(2-fluoro-5-methoxyphenyl)-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.43 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-[(5-methyl-2-pyridinyl)methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.44 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
8-Bromo-7-oxo-3b,4,5,6-tetrahydro-7H-2,6a,11b-triaza-benzo[g]cyclopenta[e]azulene-3-carboxylic acid tert-butyl ester	KI	0.45 nM
4-amino-8-[5-[(6-cyano-2-pyridinyl)methoxy]-2-fluorophenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.46 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-[(5-fluoro-2-pyridinyl)methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.48 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
CHEMBL1451229	KI	0.5 nM
4-amino-8-[2-fluoro-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.5 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
2-fluoro-5-(7-trifluoromethylimidazo[1,2-a]pyrimidin-3-yl)biphenyl-2-carbonitrile	KI	0.52 nM
4-amino-8-(5-fluoro-2-methoxypyrimidin-4-yl)-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.56 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
CHEMBL1783285	KI	0.562 nM
4-amino-8-[2-fluoro-5-[(6-methyl-3-pyridinyl)oxymethyl]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.57 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
3-(5-Methyl-isoxazol-3-yl)-6-(1-methyl-1H-[1,2,3]triazol-4-ylmethoxy)-[1,2,4]triazolo[3,4-a]phthalazine	KI	0.58 nM

ChEMBL bioactivities

1431 potent at pChembl≥5 of 1510 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	Ki	0.03	nM	CHEMBL3144849
10.22	Ki	0.06	nM	PHENAZEPAM
10.22	Ki	0.06	nM	CHEMBL3144696
10.10	Ki	0.08	nM	CGS-8216
10.10	Ki	0.08	nM	CHEMBL4243764
10.00	IC50	0.1	nM	CHEMBL454349
10.00	Ki	0.1	nM	CHEMBL3144841
9.82	Ki	0.15	nM	CHEMBL3274851
9.80	IC50	0.16	nM	CHEMBL309517
9.77	Ki	0.17	nM	CHEMBL3144615
9.70	IC50	0.2	nM	CHEMBL4747460
9.68	Ki	0.21	nM	CHEMBL3144698
9.62	IC50	0.24	nM	CHEMBL79037
9.60	Ki	0.25	nM	CHEMBL375742
9.52	Ki	0.3	nM	MK-0777
9.52	Ki	0.3	nM	AZD7325
9.52	Ki	0.3	nM	CHEMBL44533
9.51	Ki	0.31	nM	MK-0777
9.51	Ki	0.309	nM	AZD7325
9.42	Ki	0.3802	nM	CHEMBL1783284
9.40	IC50	0.3981	nM	CGS-8216
9.40	Ki	0.4	nM	CHEMBL199957
9.40	IC50	0.4	nM	CHEMBL1271047
9.39	Ki	0.4074	nM	CHEMBL1783283
9.34	IC50	0.46	nM	CHEMBL78730
9.31	IC50	0.49	nM	CHEMBL76263
9.30	IC50	0.5	nM	CHEMBL5266498
9.30	IC50	0.5	nM	CHEMBL5290464
9.30	IC50	0.5	nM	CHEMBL5280240
9.30	IC50	0.5	nM	CHEMBL49141
9.30	IC50	0.5	nM	CHEMBL1518572
9.28	Ki	0.52	nM	CHEMBL381380
9.25	Ki	0.5623	nM	CHEMBL1783285
9.24	Ki	0.58	nM	CHEMBL306422
9.23	Ki	0.59	nM	TRIAZOLAM
9.22	IC50	0.6026	nM	CGS-9896
9.22	IC50	0.6	nM	CHEMBL419096
9.22	Ki	0.6	nM	CHEMBL45198
9.22	Ki	0.6	nM	ALPRAZOLAM
9.22	Ki	0.6	nM	CHEMBL475204
9.19	Ki	0.64	nM	CHEMBL307111
9.19	Ki	0.64	nM	BRETAZENIL
9.15	Ki	0.7	nM	CHEMBL373250
9.15	Ki	0.7	nM	CHEMBL3246832
9.15	Ki	0.7	nM	CHEMBL299210
9.14	Ki	0.73	nM	CHEMBL369902
9.14	Ki	0.73	nM	CHEMBL224561
9.12	IC50	0.76	nM	CHEMBL540583
9.11	Ki	0.78	nM	CHEMBL199957
9.11	Ki	0.77	nM	CHEMBL4436326

PubChem BioAssay actives

1306 with measured affinity, of 3423 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-(4-ethynylphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	73089: Binding affinity to human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-2-beta-3-gamma-2	ki	<0.0001	uM
8-methoxy-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73089: Binding affinity to human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-2-beta-3-gamma-2	ki	0.0001	uM
2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	40988: Inhibition on Benzodiazepine receptor	ic50	0.0001	uM
8-ethynyl-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73089: Binding affinity to human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-2-beta-3-gamma-2	ki	0.0001	uM
7-bromo-5-(2-fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one	1889907: Displacement of [3H]flunitrazepam from human recombinant alpha2beta2gamma2 GABAA receptor expressed in HEK cell membrane by competitive radioligand binding assay	ki	0.0001	uM
7-bromo-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one	1889907: Displacement of [3H]flunitrazepam from human recombinant alpha2beta2gamma2 GABAA receptor expressed in HEK cell membrane by competitive radioligand binding assay	ki	0.0001	uM
2-phenyl-3aH-pyrazolo[4,3-c]quinolin-3-one	73089: Binding affinity to human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-2-beta-3-gamma-2	ki	0.0001	uM
8-bromo-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73089: Binding affinity to human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-2-beta-3-gamma-2	ki	0.0001	uM
8-chloro-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73089: Binding affinity to human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-2-beta-3-gamma-2	ki	0.0002	uM
ethyl 4-(methoxymethyl)-5-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0002	uM
2-(4-bromophenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	73089: Binding affinity to human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-2-beta-3-gamma-2	ki	0.0002	uM
13-(4-methyl-1,3-thiazol-2-yl)-15-phenyl-4,11-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2(7),3,5,13-pentaen-12-one	71234: Displacement of [3H]Ro-151788 from human GABA-A receptor alpha2 subunit expressed in L(tk) cells	ki	0.0003	uM
4-amino-8-(2-fluoro-6-methoxyphenyl)-N-propylcinnoline-3-carboxamide	1604528: Binding affinity to GABA-A alpha2 (unknown origin)	ki	0.0003	uM
7-cyclobutyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine	282666: Displacement of [3H]Ro 15-1788 from human recombinant GABAA alpha-2-beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0003	uM
7-tert-butyl-6-[(2-ethyl-1,2,4-triazol-3-yl)methoxy]-3-(2-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine	259130: Displacement of [3H]-Ro15-1788 from human recombinant GABAA alpha2 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0003	uM
ethyl 4-methyl-5-propan-2-yloxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0004	uM
4-amino-8-(2,4-dimethoxyphenyl)-7-fluoro-N-propylcinnoline-3-carboxamide	601106: Displacement of [3H]flunitrazepam from benzodiazepine binding site GABAA alpha2beta3gamma2 receptor expressed in Sf9 cells after 1 hr	ki	0.0004	uM
4-amino-N-cyclopropyl-8-(2,6-dimethoxy-3-pyridinyl)-7-fluorocinnoline-3-carboxamide	601106: Displacement of [3H]flunitrazepam from benzodiazepine binding site GABAA alpha2beta3gamma2 receptor expressed in Sf9 cells after 1 hr	ki	0.0004	uM
2-[3-(7-methylimidazo[1,2-a]pyrimidin-3-yl)phenyl]benzonitrile	260336: Displacement of [3H] Ro15-1788 from recombinant human GABAA alpha2 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0004	uM
ethyl 4-(methoxymethyl)-6-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
ethyl 4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
ethyl 6-methoxy-4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
ethyl 4-(methoxymethyl)-6-propoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
ethyl 6-hydroxy-4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
2-[2-fluoro-5-[7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]benzonitrile	259130: Displacement of [3H]-Ro15-1788 from human recombinant GABAA alpha2 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0005	uM
13-(4-methyl-1,3-thiazol-2-yl)-15-pyridin-4-yl-4,11-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2(7),3,5,13-pentaen-12-one	726245: Positive allosteric modulation of GABAA alpha2 (unknown origin)	ki	0.0006	uM
tert-butyl (7S)-14-bromo-12-oxo-2,4,11-triazatetracyclo[11.4.0.02,6.07,11]heptadeca-1(17),3,5,13,15-pentaene-5-carboxylate	73089: Binding affinity to human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-2-beta-3-gamma-2	ki	0.0006	uM
6-(2-chlorophenyl)-8-ethynyl-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine	1889907: Displacement of [3H]flunitrazepam from human recombinant alpha2beta2gamma2 GABAA receptor expressed in HEK cell membrane by competitive radioligand binding assay	ki	0.0006	uM
5-methyl-3-[6-[(2-methyltriazol-4-yl)methoxy]-[1,2,4]triazolo[3,4-a]phthalazin-3-yl]-1,2-oxazole	73082: Displacement of [3H]-Ro- 15-1788 from human GABA-A alpha-2-beta-3-gamma-2 receptor subunits expressed in Xenopus oocytes	ki	0.0006	uM
Alprazolam	1889907: Displacement of [3H]flunitrazepam from human recombinant alpha2beta2gamma2 GABAA receptor expressed in HEK cell membrane by competitive radioligand binding assay	ki	0.0006	uM
2-(4-chlorophenyl)-3aH-pyrazolo[4,3-c]quinolin-3-one	40988: Inhibition on Benzodiazepine receptor	ic50	0.0006	uM
4-amino-N-cyclopropyl-8-(3,6-dimethoxypyridazin-4-yl)-7-fluorocinnoline-3-carboxamide	601106: Displacement of [3H]flunitrazepam from benzodiazepine binding site GABAA alpha2beta3gamma2 receptor expressed in Sf9 cells after 1 hr	ki	0.0006	uM
Triazolam	73089: Binding affinity to human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-2-beta-3-gamma-2	ki	0.0006	uM
5-methyl-3-[6-[(1-methyltriazol-4-yl)methoxy]-[1,2,4]triazolo[3,4-a]phthalazin-3-yl]-1,2-oxazole	1604528: Binding affinity to GABA-A alpha2 (unknown origin)	ki	0.0006	uM
6-[(1-methylimidazol-2-yl)methoxy]-3-phenyl-[1,2,4]triazolo[3,4-a]phthalazine	72477: Binding affinity for human GABA-A receptor alpha-2-beta-3-gamma-2 subunits in L(tk-) cells	ki	0.0007	uM
7-cyclopentyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine	282666: Displacement of [3H]Ro 15-1788 from human recombinant GABAA alpha-2-beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0007	uM
8-bromo-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine	1889907: Displacement of [3H]flunitrazepam from human recombinant alpha2beta2gamma2 GABAA receptor expressed in HEK cell membrane by competitive radioligand binding assay	ki	0.0007	uM
5-fluoro-2-[2-fluoro-5-[7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]benzonitrile	260336: Displacement of [3H] Ro15-1788 from recombinant human GABAA alpha2 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0007	uM
7-tert-butyl-3-(2,5-difluorophenyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine	259130: Displacement of [3H]-Ro15-1788 from human recombinant GABAA alpha2 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0007	uM
5-[[3-(1,3-benzodioxol-5-yl)-6-iminopyridazin-1-yl]methyl]-1,2-thiazol-3-one;hydrobromide	72153: Affinity for gamma-aminobutyric-acid A receptor measured by its ability to displace [3H]gabazine antagonist from rat brain preparations.	ic50	0.0008	uM
propan-2-yl 16-(methoxymethyl)-3,6,11,14-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-1(10),2,4,6,8,12,14,16-octaene-15-carboxylate	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0008	uM
5-fluoro-2-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile	260336: Displacement of [3H] Ro15-1788 from recombinant human GABAA alpha2 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0008	uM
2-(4-chlorophenyl)-6,7,8,9-tetrahydro-1H-pyrazolo[4,3-c]quinolin-3-one	72479: In vitro displacement of [3H]Ro-151788 from human GABA-A receptor alpha-2-beta-3-gamma-2 subunits expressed in L(tk-) cells	ki	0.0008	uM
propan-2-yl 4-(methoxymethyl)-6,9,14,21-tetrazapentacyclo[11.8.0.02,10.03,8.015,20]henicosa-1(21),2,4,6,8,10,12,15(20)-octaene-5-carboxylate	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0008	uM
propan-2-yl 15-(methoxymethyl)-4-propan-2-yl-5-oxa-10,13-diazatetracyclo[7.7.0.02,6.011,16]hexadeca-1(9),2(6),3,7,11,13,15-heptaene-14-carboxylate	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0008	uM
Clonazepam	239299: Displacement of [3H]flumazenil from bovine benzodiazepine receptor GABA-A channel of brain membranes	ki	0.0008	uM
Flumazenil	1777984: Binding affinity to GABBA alpha2 (unknown origin)	ki	0.0008	uM
3-[3-tert-butyl-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]pyrazolo[1,5-d][1,2,4]triazin-7-yl]-5-methyl-1,2-oxazole	1604528: Binding affinity to GABA-A alpha2 (unknown origin)	ki	0.0008	uM
2-[7-(4-fluoro-3-pyridin-4-ylphenyl)imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol	262145: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha2 receptor plus beta-3-gamma-2 expressed in mouse L(tk-) cells	ki	0.0009	uM
15-(methoxymethyl)-14-(5-methyl-1,2-oxazol-3-yl)-4-propan-2-yl-5-oxa-3,10,13-triazatetracyclo[7.7.0.02,6.011,16]hexadeca-1(9),2(6),3,7,11,13,15-heptaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0009	uM

CTD chemical–gene interactions

53 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression	6
gamma-Aminobutyric Acid	decreases reaction, affects binding, increases activity, increases reaction	3
Carmustine	decreases expression, affects response to substance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Picrotoxin	affects binding, decreases reaction, increases activity	2
6-methoxyflavone	affects binding, increases activity, increases reaction	1
6-methoxyflavanone	affects binding, increases activity, increases reaction	1
tetramethylenedisulfotetramine	increases activity, increases response to substance, affects binding, decreases reaction	1
terbufos	increases methylation	1
sodium arsenite	decreases expression	1
picrotoxinin	increases activity, affects binding, decreases reaction	1
tert-butylbicyclophosphorothionate	affects binding, decreases reaction	1
tert-butylbicyclo-2-benzoate	affects binding, decreases reaction	1
tribromoethanol	affects binding, increases activity, increases reaction	1
fipronil	affects binding, decreases activity	1
1-(4-ethynylphenyl)-4-propyl-2,6,7-trioxabicyclo(2.2.2)octane	decreases reaction, affects binding	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	1
candoxin	increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
Sevoflurane	increases activity, increases reaction, affects binding	1
Temozolomide	affects response to substance	1
Felbamate	affects binding, increases activity	1
Cyclic AMP	affects cotreatment, increases expression	1
Ascorbic Acid	increases expression, affects cotreatment	1
Hexachlorocyclohexane	affects binding, decreases reaction	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Bicuculline	affects binding, decreases activity	1
Biological Factors	decreases expression	1
Chloral Hydrate	affects binding, increases activity, increases reaction	1

ChEMBL screening assays

385 unique, capped per target: 327 binding, 52 functional, 3 admet, 3 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3363914	Binding	Displacement of [3H]Muscimol from rat GABAA receptor at 10 uM after 90 mins by microbeta counting analysis	Griseorhodins D-F, neuroactive intermediates and end products of post-PKS tailoring modification in Griseorhodin biosynthesis. — *J Nat Prod*
CHEMBL4810229	ADMET	Inhibition of GABA A receptor (unknown origin) at 0.1 to 1 uM	Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. — *J Med Chem*
CHEMBL5335653	Toxicity	Antagonist activity at GABA-A (unknown origin)	Discovery of a Novel Bifunctional Steroid Analog, YXG-158, as an Androgen Receptor Degrader and CYP17A1 Inhibitor for the Treatment of Enzalutamide-Resistant Prostate Cancer. — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1KP	PrecisION hGABAA alpha2/beta3/gamma2-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00000437	Phase 4	COMPLETED	Tobacco Dependence in Alcoholism Treatment (Nicotine Patch/Naltrexone)
NCT00000438	Phase 4	COMPLETED	Naltrexone Treatment for Alcoholism
NCT00000441	Phase 4	COMPLETED	Drug Therapy for Alcohol Detoxification
NCT00000442	Phase 4	COMPLETED	Naltrexone for Relapse Prevention
NCT00000444	Phase 4	COMPLETED	Timing of Smoking Intervention in Alcohol Treatment (Nicotine Patch)
NCT00000445	Phase 4	COMPLETED	Use of Naltrexone in a Clinical Setting
NCT00000447	Phase 4	COMPLETED	Behavioral/Drug Therapy for Alcohol-Nicotine Dependence (Naltrexone/Nicotine Patch)
NCT00000448	Phase 4	COMPLETED	Naltrexone Treatment for Alcoholic Women
NCT00000449	Phase 4	COMPLETED	Behavior and Naltrexone Treatment for Alcoholics
NCT00000450	Phase 4	COMPLETED	Naltrexone Maintenance Treatment of Alcoholism
NCT00000452	Phase 4	COMPLETED	Naltrexone Treatment of Alcohol Dependence
NCT00000454	Phase 4	COMPLETED	Smoking Cessation in Alcoholism Treatment
NCT00000455	Phase 4	COMPLETED	Naltrexone for Early Problem Drinkers
NCT00000456	Phase 4	COMPLETED	Behavioral Therapy Plus Naltrexone for Alcoholism
NCT00004551	Phase 4	COMPLETED	Behavioral Counseling for Alcohol Dependent Smokers (Nicotine Patch)
NCT00004554	Phase 4	COMPLETED	Sertraline for Alcohol Dependence and Depression
NCT00006203	Phase 4	COMPLETED	Naltrexone, Craving, and Drinking
NCT00006204	Phase 4	COMPLETED	Drug Treatment for Depressed Alcoholics (Naltrexone/Fluoxetine)
NCT00006449	Phase 4	COMPLETED	Post-Treatment Effects of Naltrexone
NCT00006489	Phase 4	COMPLETED	Treatment for Alcoholism and Post-Traumatic Stress Disorder (Naltrexone)
NCT00018824	Phase 4	COMPLETED	Treating Alcohol Use In Older Adults With Depression
NCT00044434	Phase 4	COMPLETED	Bupropion as a Smoking Cessation Aid in Alcoholics
NCT00064844	Phase 4	COMPLETED	Combination Nicotine Replacement for Alcoholic Smokers
NCT00082199	Phase 4	COMPLETED	Study of Aripiprazole in Subjects With Alcoholism
NCT00115037	Phase 4	COMPLETED	Managing Alcoholism in People Who Do Not Respond to Naltrexone
NCT00120601	Phase 4	UNKNOWN	Trial for the Treatment of Alcohol Dependence
NCT00145847	Phase 4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148031	Phase 4	COMPLETED	Improving Hepatitis C Treatment in Injection Drug Users
NCT00159107	Phase 4	COMPLETED	Integrative Therapy in Alcoholism
NCT00167687	Phase 4	COMPLETED	Prazosin Alcohol Dependence IVR Study
NCT00223275	Phase 4	COMPLETED	Naltrexone for Bipolar Disorder and Alcohol Dependence
NCT00226109	Phase 4	SUSPENDED	Clinical Trial Studying the Effects of Spironolactone on Heart and Skeletal Muscle Function in Chronic Alcoholics
NCT00246441	Phase 4	COMPLETED	Paroxetine for Comorbid Social Anxiety Disorder and Alcoholism
NCT00249379	Phase 4	TERMINATED	Study of Acamprosate to Prevent Alcohol Relapse in Criminal Justice Supervisees
NCT00261872	Phase 4	COMPLETED	Treatment of Patients With Alcoholism and Attention Deficit Disorder
NCT00317031	Phase 4	COMPLETED	Individually Adapted Therapy of Alcoholism
NCT00325182	Phase 4	COMPLETED	The Effects of Levetiracetam on Alcohol Dependent Subjects
NCT00329407	Phase 4	COMPLETED	The Effects of Topiramate on Alcohol Use in Alcohol Dependent Subjects
NCT00330174	Phase 4	COMPLETED	Acamprosate in Alcoholics With Comorbid Anxiety or Depression
NCT00352469	Phase 4	COMPLETED	Trial of Seroquel SR for Alcohol Dependence and Comorbid Anxiety
NCT00366626	Phase 4	COMPLETED	Effectiveness of Naltrexone Versus Placebo to Reduce Craving for Alcohol With Evaluation of Genetic Variability.
NCT00368550	Phase 4	COMPLETED	Sertraline Pharmacotherapy for Alcoholism Subtypes
NCT00368862	Phase 4	COMPLETED	Efficacy Study of Memantine Hydrochloride and Escitalopram for the Treatment of Co-Morbid Depression and Alcoholism.
NCT00369408	Phase 4	COMPLETED	Targeted Naltrexone for Problem Drinkers
NCT00381043	Phase 4	COMPLETED	Study of Campral (Acamprosate) for Alcohol Dependence in a Family Medicine Clinic
NCT00419315	Phase 4	COMPLETED	A Randomized Clinical Trial of Alcohol Care Management
NCT00431262	Phase 4	UNKNOWN	Antabuse in Severe Alcoholism: an Open Controlled Study
NCT00435435	Phase 4	COMPLETED	Comparative Trial Of Disulfiram, Naltrexone And Acamprosate In The Treatment Of Alcohol Dependence
NCT00449007	Phase 4	TERMINATED	Fluoxetine and Bupropion to Treat Patients With Depression and Alcoholism
NCT00452543	Phase 4	COMPLETED	Acamprosate Added to Escitalopram and Behavioral Treatment for Comorbid Depression and Alcoholism
NCT00453609	Phase 4	COMPLETED	Injectable Naltrexone Treatment of Alcohol Dependence in Serious Mental Illness (SMI)
NCT00453804	Phase 4	COMPLETED	Injectable Versus Oral Naltrexone Treatment of Alcohol Dependence In Serious Mental Illness (SMI)
NCT00457197	Phase 4	COMPLETED	Quetiapine for Bipolar Disorder and Alcohol Dependence
NCT00461890	Phase 4	TERMINATED	Long-Acting Injectable Naltrexone Treatment of Alcohol Dependence in Primary Care vs. in Specialized Chemical Dependence Treatment: A Pilot Trial
NCT00466661	Phase 4	COMPLETED	Acamprosate vs. Placebo in Bipolar Alcoholics
NCT00511836	Phase 4	COMPLETED	ALK21-018: Effects of Medisorb® Naltrexone (VIVITROL®) on Alcohol Craving in Treatment-seeking, Alcohol-dependent Adults
NCT00568958	Phase 4	COMPLETED	Naltrexone for Heavy Drinking in Young Adults
NCT00572117	Phase 4	COMPLETED	Adjunctive Topiramate for Treatment of Alcohol Dependence in Patients With Bipolar Disorder
NCT00595556	Phase 4	COMPLETED	Zonisamide vs. Placebo in the Treatment of Alcohol Dependence
NCT00620750	Phase 4	COMPLETED	Extended-release Naltrexone for Alcohol Dependence in Primary Care

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for GABRA2 across ~30M SureChEMBL compounds — explore on Sugi Predict.