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): 373 total — 6 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes — 46 molecules with ChEMBL bioactivity
• 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: 25 — 19 protein_coding, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

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

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
ENSE00001919244	46243548	46250604
ENSE00003458320	46310173	46310255
ENSE00003494083	46386074	46386189
ENSE00003496336	46312496	46312716
ENSE00003531854	46303460	46303612
ENSE00003558735	46388636	46388716
ENSE00003654430	46261926	46262128

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.

FANTOM5 promoters (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

284 total, 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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting GABRA2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

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

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

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabra2a	ENSDARG00000091459
danio_rerio		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)

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), 1 shown:

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

UniProt features (56 total): strand 15, helix 10, 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)

8 structures.

PDB	Method	Resolution (Å)
9CRV	ELECTRON MICROSCOPY	3.18
9CT0	ELECTRON MICROSCOPY	3.19
9CX7	ELECTRON MICROSCOPY	3.3
9CXC	ELECTRON MICROSCOPY	3.3
9CXB	ELECTRON MICROSCOPY	3.33
9CSB	ELECTRON MICROSCOPY	3.34
9CTV	ELECTRON MICROSCOPY	3.36
9CTJ	ELECTRON MICROSCOPY	3.74

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab): 7 — 9CRV, 9CT0, 9CTJ, 9CTV, 9CX7, 9CXB, 9CXC

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): 94; 157

Disulfide bonds (1): 166–180

Glycosylation sites (2): 38, 138

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-977443	GABA receptor activation

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 (18): 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), cell projection (GO:0042995), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Neurotransmitter receptors and postsynaptic signal transmission	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synapse	3
cellular anatomical structure	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
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

Protein interactions and networks

STRING

1492 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRA2	CHRM2	P08172	808
GABRA2	ACADM	P11310	705
GABRA2	DRD2	P14416	600
GABRA2	SLC6A4	P31645	595
GABRA2	ADH1B	P00325	582
GABRA2	OPRM1	P35372	579
GABRA2	ANKK1	Q8NFD2	574
GABRA2	GABBR2	O75899	571
GABRA2	DRD4	P21917	561
GABRA2	PGM1	P36871	548
GABRA2	GABRB1	P18505	517
GABRA2	GRIA3	P42263	517
GABRA2	ALDH2	P05091	513
GABRA2	COMT	P21964	511
GABRA2	ADH7	P40394	507

IntAct

5 interactions, top by confidence:

A	B	Type	Score
EGFR	NDUFA4	psi-mi:“MI:0914”(association)	0.530
EGFR	GABRA2	psi-mi:“MI:0915”(physical association)	0.500
GABRA2	E7	psi-mi:“MI:0915”(physical association)	0.370
GABRA2	MDM2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): GABRA2 (Synthetic Lethality), GABRG2 (FRET), GABRA2 (Affinity Capture-Western), GABRA2 (Affinity Capture-MS), GABRA2 (Two-hybrid), GABRA2 (Two-hybrid), GABRA2 (Two-hybrid), GABRA2 (Two-hybrid)

ESM2 similar proteins: D1LYT2, O94925, P08219, P08220, P0C2W5, P10063, P10064, P14867, P15431, P16305, P18505, P18507, P18508, P19019, P19150, P19969, P20236, P21548, P22300, P22723, P23574, P23576, P24045, P26048, P26049, P27681, P28472, P28473, P30191, P31644, P34903, P47869, P47870, P50571, P62812, P62813, P63079, P63080, P63137, P63138

Diamond homologs: A8MPY1, D1LYT2, F1R8P4, G5EBR3, O00591, O09028, O14764, O18276, O75311, O93430, P07727, P08219, P08220, P0C2W5, P10063, P10064, P14867, P15431, P16305, P18505, P18506, P18507, P18508, P19019, P19150, P19969, P20236, P20237, P20781, P21548, P22300, P22723, P22771, P22933, P23415, P23416, P23574, P23576, P24045, P24046

SIGNOR signaling

2 interactions.

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	11
Uncertain significance	152
Likely benign	160
Benign	18

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1675200	NM_000807.4(GABRA2):c.855del (p.Phe285fs)	Pathogenic
3338107	NM_000807.4(GABRA2):c.988_989insTTATG (p.Glu330fs)	Pathogenic
4526429	NM_000807.4(GABRA2):c.895A>C (p.Ser299Arg)	Pathogenic
689388	NM_000807.4(GABRA2):c.871C>G (p.Leu291Val)	Pathogenic
689389	NM_000807.4(GABRA2):c.788T>C (p.Met263Thr)	Pathogenic
689390	NM_000807.4(GABRA2):c.975C>A (p.Phe325Leu)	Pathogenic
1919477	NM_000807.4(GABRA2):c.850G>A (p.Val284Met)	Likely pathogenic
2635567	NM_000807.4(GABRA2):c.883A>T (p.Thr295Ser)	Likely pathogenic
2718827	NM_000807.4(GABRA2):c.124T>A (p.Phe42Ile)	Likely pathogenic
3338106	NM_000807.4(GABRA2):c.644T>C (p.Leu215Ser)	Likely pathogenic
3338108	NM_000807.4(GABRA2):c.460C>G (p.Leu154Val)	Likely pathogenic
3342660	NM_000807.4(GABRA2):c.197C>T (p.Thr66Ile)	Likely pathogenic
3377080	NM_000807.4(GABRA2):c.850G>T (p.Val284Leu)	Likely pathogenic
3602196	NM_000807.4(GABRA2):c.281G>A (p.Arg94Gln)	Likely pathogenic
4074841	NM_000807.4(GABRA2):c.851T>G (p.Val284Gly)	Likely pathogenic
689387	NM_000807.4(GABRA2):c.875C>A (p.Thr292Lys)	Likely pathogenic
976773	NM_000807.4(GABRA2):c.875C>T (p.Thr292Ile)	Likely pathogenic

SpliceAI

2274 predictions. Top by Δscore:

Variant	Effect	Δscore
4:46262126:CTC:C	acceptor_gain	1.0000
4:46305707:TGCAT:T	acceptor_gain	1.0000
4:46305709:CAT:C	acceptor_gain	1.0000
4:46305712:C:CC	acceptor_gain	1.0000
4:46310171:A:AC	donor_gain	1.0000
4:46310172:C:CC	donor_gain	1.0000
4:46310172:CAG:C	donor_gain	1.0000
4:46312491:CATA:C	donor_loss	1.0000
4:46312492:ATAC:A	donor_loss	1.0000
4:46312494:A:C	donor_loss	1.0000
4:46312495:C:CT	donor_loss	1.0000
4:46312495:CCT:C	donor_gain	1.0000
4:46312712:TATTC:T	acceptor_gain	1.0000
4:46312714:TTC:T	acceptor_gain	1.0000
4:46312715:TC:T	acceptor_gain	1.0000
4:46312716:CC:C	acceptor_gain	1.0000
4:46312716:CCT:C	acceptor_loss	1.0000
4:46312717:C:CC	acceptor_gain	1.0000
4:46312718:T:A	acceptor_loss	1.0000
4:46368846:AACCC:A	donor_gain	1.0000
4:46386068:TTTTA:T	donor_loss	1.0000
4:46386069:TTTAC:T	donor_loss	1.0000
4:46386070:TTA:T	donor_loss	1.0000
4:46386071:TA:T	donor_loss	1.0000
4:46386072:A:AG	donor_loss	1.0000
4:46386075:T:TA	donor_gain	1.0000
4:46386076:C:A	donor_gain	1.0000
4:46388273:G:C	donor_gain	1.0000
4:46388727:CCA:C	acceptor_gain	1.0000
4:46388728:C:CT	acceptor_gain	1.0000

AlphaMissense

2985 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:46250355:A:G	W437R	1.000
4:46250355:A:T	W437R	1.000
4:46250365:A:C	N433K	1.000
4:46250365:A:T	N433K	1.000
4:46250377:A:C	F429L	1.000
4:46250377:A:T	F429L	1.000
4:46250379:A:G	F429L	1.000
4:46250387:G:C	P426R	1.000
4:46250387:G:T	P426Q	1.000
4:46250389:A:C	F425L	1.000
4:46250389:A:T	F425L	1.000
4:46250391:A:G	F425L	1.000
4:46250398:T:A	R422S	1.000
4:46250398:T:G	R422S	1.000
4:46250411:T:A	D418V	1.000
4:46250411:T:G	D418A	1.000
4:46250412:C:G	D418H	1.000
4:46261980:A:C	N335K	1.000
4:46261980:A:T	N335K	1.000
4:46261984:A:T	V334D	1.000
4:46261990:G:T	A332E	1.000
4:46261991:C:G	A332P	1.000
4:46261992:A:C	F331L	1.000
4:46261992:A:T	F331L	1.000
4:46261993:A:C	F331C	1.000
4:46261993:A:G	F331S	1.000
4:46261994:A:G	F331L	1.000
4:46261994:A:T	F331I	1.000
4:46261995:T:A	E330D	1.000
4:46261995:T:G	E330D	1.000

dbSNP variants (sampled 300 via entrez): RS1000087494 (4:46306360 G>A), RS1000106884 (4:46306102 A>G), RS1000125527 (4:46322774 T>C), RS1000128358 (4:46266883 A>G), RS1000132891 (4:46258968 AAG>A), RS1000138581 (4:46298846 T>C), RS1000150554 (4:46279037 A>G), RS1000157098 (4:46271894 T>G), RS1000161149 (4:46319132 T>C,G), RS1000181840 (4:46361218 G>A), RS1000210146 (4:46272157 T>C), RS1000234181 (4:46361549 C>G,T), RS1000241452 (4:46311899 G>A,T), RS1000284495 (4:46299213 T>C), RS1000287907 (4:46353158 T>G)

Disease associations

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

GenCC curated gene-disease

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

Mondo (5): developmental and epileptic encephalopathy, 78 (MONDO:0032812), alcohol dependence (MONDO:0007079), intellectual disability (MONDO:0001071), developmental and epileptic encephalopathy (MONDO:0100620), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

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

HPO phenotypes

62 total (30 of 62 shown, 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	Reduced tendon reflexes
HP:0001319	Neonatal hypotonia
HP:0001336	Myoclonus

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002547_4	Epilepsy	2.000000e-07
GCST006624_8	Systolic blood pressure	3.000000e-11
GCST007324_61	Adventurousness	1.000000e-15
GCST007325_64	General risk tolerance (MTAG)	2.000000e-18
GCST007353_6	Generalized epilepsy	4.000000e-08

EFO canonical traits (2, from GWAS)

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

MeSH disease descriptors (1)

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)

Molecules with ChEMBL bioactivity

46 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 629,660 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1082407	ENZALUTAMIDE	4	9,652
CHEMBL12	DIAZEPAM	4	92,281
CHEMBL1544	LIOTHYRONINE	4	23,700
CHEMBL1568698	GANAXOLONE	4	1,657
CHEMBL207538	BREXANOLONE	4	1,585
CHEMBL3183409	APALUTAMIDE	4	4,076
CHEMBL407	FLUMAZENIL	4	7,150
CHEMBL452	CLONAZEPAM	4	33,297
CHEMBL13280	FLUNITRAZEPAM	4	11,549
CHEMBL1521	ZALEPLON	4	9,958
CHEMBL451	CHLORDIAZEPOXIDE	4	36,533
CHEMBL646	TRIAZOLAM	4	21,589
CHEMBL911	ZOLPIDEM	4	17,821
CHEMBL526	PROPOFOL	4	28,835
CHEMBL1522	ESZOPICLONE	4	6,548
CHEMBL448	PENTOBARBITAL	4	49,933
CHEMBL661	ALPRAZOLAM	4	130,677
CHEMBL681	ETOMIDATE	4	8,462
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1106	EPINASTINE	4
CHEMBL146095	GLAFENINE	4
CHEMBL222559	TIPRANAVIR	4
CHEMBL297302	BENPERIDOL	4
CHEMBL3187365	ASENAPINE	4
CHEMBL408	TROGLITAZONE	4
CHEMBL42	CLOZAPINE	4
CHEMBL515	CHLORAMBUCIL	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL639	AZELASTINE	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11503014	GABRA2	3	2.00	1	cocaine
rs279858	GABRA2	3	1.00	1	sevoflurane
rs279847	GABRA2		0.00	0

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)

393 measured of 410 human assays (420 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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
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
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
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
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
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
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
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
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
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
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
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
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
4-amino-8-(3-fluoro-6-methyl-2-pyridinyl)-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.59 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-[(6-methyl-3-pyridinyl)methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.59 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-[[5-(trifluoromethyl)-2-pyridinyl]methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.61 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-[(1-methyltriazol-4-yl)methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.65 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-[(5-methyl-1,2,4-oxadiazol-3-yl)methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.65 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-[[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.66 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-(5-fluoro-2-methyl-4-pyridinyl)-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.67 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
Halcion	KI	0.68 nM
FG 8205	KI	0.68 nM
4-amino-8-(5-fluoro-2-methoxy-4-pyridinyl)-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.68 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-[[4-(hydroxymethyl)-2-pyridinyl]methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.7 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-(oxan-4-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.7 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[5-[(5-chloro-2-pyridinyl)methoxy]-2-fluorophenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.72 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[5-[(2-cyano-4-fluorophenyl)methoxy]-2-fluorophenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.73 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-(1H-pyrazol-5-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.78 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-2-oxo-N-propyl-8-[6-(trifluoromethoxy)-2-pyridinyl]-1H-quinoline-3-carboxamide	KI	0.79 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-(3,5-difluoro-2-pyridinyl)-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.87 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
US20250197368, Example 122	KI	0.89 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-(oxetan-3-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.9 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-[(5-methoxy-2-pyridinyl)methoxy]phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.92 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-(1H-imidazol-5-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.98 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS

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

1297 with measured affinity, of 3399 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	affects cotreatment, increases expression, affects expression, decreases methylation	6
gamma-Aminobutyric Acid	affects binding, increases activity, increases reaction, decreases 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	increases activity, increases reaction, affects binding	1
6-methoxyflavanone	increases reaction, affects binding, increases activity	1
tetramethylenedisulfotetramine	increases response to substance, affects binding, decreases reaction, increases activity	1
terbufos	increases methylation	1
sodium arsenite	decreases expression	1
picrotoxinin	decreases reaction, increases activity, affects binding	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	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
candoxin	increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
Sevoflurane	increases reaction, affects binding, increases activity	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)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00000437	PHASE4	COMPLETED	Tobacco Dependence in Alcoholism Treatment (Nicotine Patch/Naltrexone)
NCT00000438	PHASE4	COMPLETED	Naltrexone Treatment for Alcoholism
NCT00000441	PHASE4	COMPLETED	Drug Therapy for Alcohol Detoxification
NCT00000442	PHASE4	COMPLETED	Naltrexone for Relapse Prevention
NCT00000444	PHASE4	COMPLETED	Timing of Smoking Intervention in Alcohol Treatment (Nicotine Patch)
NCT00000445	PHASE4	COMPLETED	Use of Naltrexone in a Clinical Setting
NCT00000447	PHASE4	COMPLETED	Behavioral/Drug Therapy for Alcohol-Nicotine Dependence (Naltrexone/Nicotine Patch)
NCT00000448	PHASE4	COMPLETED	Naltrexone Treatment for Alcoholic Women
NCT00000449	PHASE4	COMPLETED	Behavior and Naltrexone Treatment for Alcoholics
NCT00000450	PHASE4	COMPLETED	Naltrexone Maintenance Treatment of Alcoholism
NCT00000452	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Dependence
NCT00000454	PHASE4	COMPLETED	Smoking Cessation in Alcoholism Treatment
NCT00000455	PHASE4	COMPLETED	Naltrexone for Early Problem Drinkers
NCT00000456	PHASE4	COMPLETED	Behavioral Therapy Plus Naltrexone for Alcoholism
NCT00004551	PHASE4	COMPLETED	Behavioral Counseling for Alcohol Dependent Smokers (Nicotine Patch)
NCT00004554	PHASE4	COMPLETED	Sertraline for Alcohol Dependence and Depression
NCT00006203	PHASE4	COMPLETED	Naltrexone, Craving, and Drinking
NCT00006204	PHASE4	COMPLETED	Drug Treatment for Depressed Alcoholics (Naltrexone/Fluoxetine)
NCT00006449	PHASE4	COMPLETED	Post-Treatment Effects of Naltrexone
NCT00006489	PHASE4	COMPLETED	Treatment for Alcoholism and Post-Traumatic Stress Disorder (Naltrexone)
NCT00018824	PHASE4	COMPLETED	Treating Alcohol Use In Older Adults With Depression
NCT00044434	PHASE4	COMPLETED	Bupropion as a Smoking Cessation Aid in Alcoholics
NCT00064844	PHASE4	COMPLETED	Combination Nicotine Replacement for Alcoholic Smokers
NCT00082199	PHASE4	COMPLETED	Study of Aripiprazole in Subjects With Alcoholism
NCT00115037	PHASE4	COMPLETED	Managing Alcoholism in People Who Do Not Respond to Naltrexone
NCT00120601	PHASE4	UNKNOWN	Trial for the Treatment of Alcohol Dependence
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148031	PHASE4	COMPLETED	Improving Hepatitis C Treatment in Injection Drug Users
NCT00159107	PHASE4	COMPLETED	Integrative Therapy in Alcoholism
NCT00167687	PHASE4	COMPLETED	Prazosin Alcohol Dependence IVR Study
NCT00223275	PHASE4	COMPLETED	Naltrexone for Bipolar Disorder and Alcohol Dependence
NCT00226109	PHASE4	SUSPENDED	Clinical Trial Studying the Effects of Spironolactone on Heart and Skeletal Muscle Function in Chronic Alcoholics
NCT00246441	PHASE4	COMPLETED	Paroxetine for Comorbid Social Anxiety Disorder and Alcoholism
NCT00249379	PHASE4	TERMINATED	Study of Acamprosate to Prevent Alcohol Relapse in Criminal Justice Supervisees
NCT00261872	PHASE4	COMPLETED	Treatment of Patients With Alcoholism and Attention Deficit Disorder
NCT00317031	PHASE4	COMPLETED	Individually Adapted Therapy of Alcoholism
NCT00325182	PHASE4	COMPLETED	The Effects of Levetiracetam on Alcohol Dependent Subjects
NCT00329407	PHASE4	COMPLETED	The Effects of Topiramate on Alcohol Use in Alcohol Dependent Subjects
NCT00330174	PHASE4	COMPLETED	Acamprosate in Alcoholics With Comorbid Anxiety or Depression
NCT00352469	PHASE4	COMPLETED	Trial of Seroquel SR for Alcohol Dependence and Comorbid Anxiety