GABRB3

Summary

GABRB3 (gamma-aminobutyric acid type A receptor subunit beta3, HGNC:4083) is a protein-coding gene on chromosome 15q12, encoding Gamma-aminobutyric acid receptor subunit beta-3 (P28472). Beta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

This gene encodes a member of the ligand-gated ionic channel family. The encoded protein is one the subunits of a multi-subunit chloride channel that serves as the receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter of the mammalian nervous system. This gene is located on the long arm of chromosome 15 in a cluster with two other genes encoding related subunits of the family. This gene may be associated with the pathogenesis of several disorders including Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. Alternatively spliced transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 2562 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 781 total — 47 pathogenic, 46 likely-pathogenic
• Phenotypes (HPO): 58
• Druggable target: yes — 32 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000814

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4083
Approved symbol	GABRB3
Name	gamma-aminobutyric acid type A receptor subunit beta3
Location	15q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166206
Ensembl biotype	protein_coding
OMIM	137192
Entrez	2562

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 12 protein_coding_CDS_not_defined, 7 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron

ENST00000299267, ENST00000311550, ENST00000400188, ENST00000541819, ENST00000545868, ENST00000554556, ENST00000554722, ENST00000555094, ENST00000555632, ENST00000556166, ENST00000556636, ENST00000557641, ENST00000557765, ENST00000621499, ENST00000635832, ENST00000635994, ENST00000636466, ENST00000636512, ENST00000636690, ENST00000637226, ENST00000637293, ENST00000637893, ENST00000638099, ENST00000638149

RefSeq mRNA: 5 — MANE Select: NM_000814 NM_000814, NM_001191320, NM_001191321, NM_001278631, NM_021912

CCDS: CCDS10018, CCDS10019, CCDS53920, CCDS53921

Canonical transcript exons

ENST00000311550 — 9 exons

Exon	Start	End
ENSE00002209380	26543552	26548134
ENSE00002510502	26772883	26773066
ENSE00003471865	26583332	26583414
ENSE00003477610	26772402	26772469
ENSE00003577196	26580319	26580456
ENSE00003578006	26772681	26772772
ENSE00003642556	26567581	26567733
ENSE00003648318	26560932	26561176
ENSE00003673107	26621314	26621534

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 98.03.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1029 / max 118.0079, expressed in 590 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149032	3.5849	389
149034	0.7019	204
149028	0.4361	199
149033	0.1688	56
149027	0.0632	24
149030	0.0536	21
149029	0.0477	17
149036	0.0318	16
149039	0.0119	4
149038	0.0029	3

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	98.03	gold quality
cortical plate	UBERON:0005343	97.24	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.85	gold quality
entorhinal cortex	UBERON:0002728	96.51	gold quality
endothelial cell	CL:0000115	95.63	gold quality
parietal lobe	UBERON:0001872	95.17	gold quality
postcentral gyrus	UBERON:0002581	94.93	gold quality
superior frontal gyrus	UBERON:0002661	94.93	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.84	gold quality
islet of Langerhans	UBERON:0000006	93.35	gold quality
prefrontal cortex	UBERON:0000451	92.00	gold quality
occipital lobe	UBERON:0002021	91.99	gold quality
primary visual cortex	UBERON:0002436	91.65	gold quality
lateral globus pallidus	UBERON:0002476	91.00	gold quality
nucleus accumbens	UBERON:0001882	90.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.95	gold quality
frontal cortex	UBERON:0001870	90.87	gold quality
frontal lobe	UBERON:0016525	90.86	gold quality
cerebral cortex	UBERON:0000956	90.38	gold quality
ganglionic eminence	UBERON:0004023	90.27	gold quality
neocortex	UBERON:0001950	90.16	gold quality
right frontal lobe	UBERON:0002810	89.95	gold quality
temporal lobe	UBERON:0001871	89.84	gold quality
telencephalon	UBERON:0001893	89.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.33	gold quality
forebrain	UBERON:0001890	88.89	gold quality
Ammon’s horn	UBERON:0001954	88.55	gold quality
brain	UBERON:0000955	87.86	gold quality
caudate nucleus	UBERON:0001873	87.64	gold quality
cerebellar cortex	UBERON:0002129	87.56	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	91.41
E-HCAD-25	yes	88.56
E-GEOD-137537	yes	13.75
E-MTAB-5061	yes	13.35
E-GEOD-81547	yes	7.51
E-ANND-3	yes	6.35
E-GEOD-81608	yes	5.40
E-CURD-11	no	115.48
E-GEOD-83139	no	4.01
E-MTAB-4850	no	0.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATOH7, EGR3, FOSL1, HOXD3, JUND, MEF2A, MYOD1, NR1I3, PITX2, REST, SP1, TCF12, TCF3

miRNA regulators (miRDB)

183 targeting GABRB3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4692	100.00	67.32	2066
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• linkage disequilibrium in cleft lip +/- cleft palate (PMID:11810291)
• Association between a GABRB3 polymorphism and autism (PMID:11920158)
• The presence of inherited insomnia in the family of the affected individual suggests a possible link between insomnia and the mutation beta3(R192H). (PMID:12189488)
• modeling of molecular configuration (PMID:12225856)
• using full-length or truncated chimeric subunits it was demonstrated that homologous sequences from beta 3 are important for assembly of GABA(A) receptors composed of alpha(1), beta(3), and gamma(2) subunits (PMID:12367595)
• Lack of anomalies in 15q11-q13 region may be related to small number of probands, heterogenity of studied group, and small number of studied loci and markers. (PMID:12491987)
• This report indicates pronounced adaptive changes in the expression of these GABA(A) receptor subunits related to seizure activity and indicates altered assembly of GABA(A) receptors in temporal lobe epilepsy. (PMID:14503638)
• No significant difference in mRNA expression is found between the control and alcoholic case groups in either the superior frontal or motor cortex for the GABA A beta 3 isoform (PMID:15337300)
• Reduced expression of GABRB3 is associated with Rett, Angelman and autism (PMID:15615769)
• the expression of the GABAA receptor pi subunit may play an important role in the pathogenesis of pancreatic cancer (PMID:15767729)
• Our data indicated that the haplotype ‘GACTCT’ (p = 0.00215, frequency = 53.6%) was overtransmitted which suggests that GABRB2 is in linkage disequilibrium with schizophrenia in the Chinese Han population. (PMID:16023997)
• Reduced expression of the GABRB3 gene could therefore be one potential cause for the development of Childhood Absence Epilepsy. (PMID:16835263)
• alpha4beta3gamma2L receptors have unique kinetic properties that limit the range of GABA applications to which they can respond maximally. (PMID:17124266)
• study failed to replicate an association of the common GABRB3 exon 1a promoter SNP rs4906902 with childhood absence epilepsy. no evidence that the common functional C-variant confers a substantial epileptogenic effect to a broad spectrum of IGE syndromes (PMID:17215107)
• Altered crosstalk between RA, GABAergic, and TGF-beta signaling systems could be involved in human cleft palate fibroblast phenotype. (PMID:17225872)
• finding suggested that single-nucleotide polymorphisms in GABRB3 may play a significant role in the genetic predisposition to autism spectrum disorders in the Korean population (PMID:17230033)
• The results indicate that human hepatocellular carcinoma (HCC) tissues are depolarized compared with adjacent nontumor tissues, and hepatic GABAA-beta3 receptor expression is down-regulated in human HCC. (PMID:17326191)
• These results suggest that MeCP2 acts as a chromatin organizer for optimal expression of both alleles of GABRB3 in neurons. (PMID:17339270)
• Subjects with schizophrenia exhibited expression deficits in GABRB3. (PMID:17471287)
• study found mutations of GABRA1, GABRB3, and GABRG2 appear not to play a major role in the development of familial primary dystonia (PMID:17880575)
• observed no significant difference in allelic frequencies or genotypic distributions of the 11 SNPs of intron 3 of GABRB3 between patients and controls (PMID:17957331)
• In the SNr GABA(A) receptors contain alpha(1), alpha(3), beta(2,3), and gamma(2) subunits and are localized in a weblike network over the cell soma, dendrites, and spines of SNr parvalbumin-positive nonpigmented neurons. (PMID:18085588)
• histamine modulates heteromultimeric GABA(A) receptors and may thus represent an endogenous ligand for an allosteric site (PMID:18281286)
• The G1- alleles of the GABRB3 in children of alcoholics were significantly higher than nonCOAs. (PMID:18358985)
• gene is involved in the pathogenesis of cleft lip with or without cleft palate in the Japanese population (PMID:18452349)
• Mutated GABRB3 could cause absence seizures through a gain in glycosylation of mutated exon 1a and exon 2, affecting maturation and trafficking of GABAR from endoplasmic reticulum to cell surface and resulting in reduced GABA-evoked currents. (PMID:18514161)
• three distinct sets of amino acid residues in the N-terminal extracellular domain of the hbeta1 subunit, which when mutated to the homologous residue in hbeta3 allow expression as a functional homomeric receptor (PMID:18650446)
• Data show that GABRB3 is significantly altered in cerebellum and significant reductions in parietal cortex in subjects with autism. (PMID:18821008)
• GABRB3 may contribute differently to the cleft phenotype in Iowans and in Filipinos, with a stronger effect in cases with palate involvement in Iowa, versus an effect in cases with involvement only of the lip in the Philippines. (PMID:18837046)
• The data provide preliminary evidence that GABRB3 gene is associated with autism spectrum disorders in Korea. (PMID:19430570)
• This study provides evidence of an association between a specific GABA(A) receptor defect and autism, direct evidence that this defect causes synaptic dysfunction that is autism relevant and maternal risk effect in the 15q11-q13 autism duplication region. (PMID:19935738)
• Gaba (A) beta1 and beta3 receptor subunit mRNA levels in the dorsolateral prefrontal cortex are not altered in schizophrenia. (PMID:20843900)
• Our data suggest the K289M mutation in gamma2 confers GABA(A)Rs with enhanced sensitivity of their membrane diffusion to neuronal activity (PMID:21908847)
• In comparison to healthy donors, chronic hepatitis C patients were found to present an increase in the expression of gamma-aminobutyric acid A receptor alpha1 subunit and a decrease in the expression of beta3 subunit in their blood mononuclear leukocytes. (PMID:22080424)
• Photoaffinity labeling and pepetide mapping data suggest that a homologous etomidate/general anesthetic binding site exists at the beta3-beta3 subunit interface in alpha1beta3 GABA receptor type A, specifically involving beta3-Met227. (PMID:22243422)
• Our results suggest both a mechanism for mutation-induced hyperexcitability and a novel role for the GABRB3 subunit N-terminal alpha-helix in receptor assembly and gating. (PMID:22303015)
• results provide additional evidence that GABRB3 and MAOB/NDP gene regions might constitute risk factors for hallucinations and delusions in schizophrenia. (PMID:22414661)
• The haplotype of C-A in rs4906902 and rs8179184 loci in the promoter of GABRB3 gene may be maternally inherited and positively associated with schizophrenia. (PMID:22812221)
• With a weak association, data do not support the hypothesis that the GABRB3 variants are a cause of nonsyndromic cleft lip and/or palate (PMID:23438326)
• Specificity of intersubunit general anesthetic-binding sites in the transmembrane domain of the human alpha1beta3gamma2 gamma-aminobutyric acid type A (GABAA) receptor. (PMID:23677991)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabrb3	ENSDARG00000023771
mus_musculus	Gabrb3	ENSMUSG00000033676
rattus_norvegicus	Gabrb3	ENSRNOG00000060599

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), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), 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 beta-3 — P28472 (reviewed: P28472)

Alternative names: GABA(A) receptor subunit beta-3

All UniProt accessions (8): A0A1B0GU30, A0A1B0GVW3, P28472, F5H7N0, G3V373, G3V4W7, H0YJU6, X5DQY4

UniProt curated annotations — full annotation on UniProt →

Function. Beta 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 interface(s). GABAARs containing beta-3/GABRB3 subunit are found at both synaptic and extrasynaptic sites. 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. GABAARs containing alpha-1 and beta-3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation. Extrasynaptic beta-3 receptors contribute to the tonic GABAergic inhibition. GABAARs containing alpha-1, beta-3 and epsilon subunits may also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings. Beta-containing GABAARs can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness. Plays an important role in somatosensation and in the production of antinociception.

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) chains, each subunit exhibiting distinct physiological and pharmacological properties. Can form functional homopentamers (in vitro). Interacts with UBQLN1. May interact with KIF21B. Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3. Interacts with LHFPL4. Interacts with GIT1; this interaction is required for synaptic GABRB3 surface stability and inhibitory synapse strength.

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

Disease relevance. Epilepsy, childhood absence 5 (ECA5) [MIM:612269] A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Absence seizures may either remit or persist into adulthood. Disease susceptibility is associated with variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 43 (DEE43) [MIM:617113] 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. DEE43 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Potentiated by histamine.

Domain organisation. 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. GABRB3 variants may be associated with insomnia, a condition of inability to initiate or maintain sleep [MIM:137192].

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB3 sub-subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
P28472-1	1	yes
P28472-2	2
P28472-3	3
P28472-4	4

RefSeq proteins (5): NP_000805, NP_001178249, NP_001178250, NP_001265560, NP_068712 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002289	GABAAb_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

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (76 total): sequence variant 17, strand 13, helix 11, binding site 10, topological domain 5, turn 5, transmembrane region 4, glycosylation site 3, splice variant 3, sequence conflict 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

95 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7A5V	ELECTRON MICROSCOPY	1.7
9EQG	ELECTRON MICROSCOPY	2.4
6QFA	ELECTRON MICROSCOPY	2.49
7QN5	ELECTRON MICROSCOPY	2.5
9FAS	ELECTRON MICROSCOPY	2.5
9FEU	ELECTRON MICROSCOPY	2.5
9FFU	ELECTRON MICROSCOPY	2.5
9G2E	ELECTRON MICROSCOPY	2.5
9FEX	ELECTRON MICROSCOPY	2.6
8PET	ELECTRON MICROSCOPY	2.6
9FGG	ELECTRON MICROSCOPY	2.6
9FAJ	ELECTRON MICROSCOPY	2.6
9FAK	ELECTRON MICROSCOPY	2.6
7QNE	ELECTRON MICROSCOPY	2.7
9FG7	ELECTRON MICROSCOPY	2.7
9FG9	ELECTRON MICROSCOPY	2.7
9G2D	ELECTRON MICROSCOPY	2.7
7PBZ	ELECTRON MICROSCOPY	2.79
9FF2	ELECTRON MICROSCOPY	2.8
9FFL	ELECTRON MICROSCOPY	2.8
9FFV	ELECTRON MICROSCOPY	2.8
9FAP	ELECTRON MICROSCOPY	2.8
7QN6	ELECTRON MICROSCOPY	2.9
7QN9	ELECTRON MICROSCOPY	2.9
7QNC	ELECTRON MICROSCOPY	2.9
9FEY	ELECTRON MICROSCOPY	2.9
9FG8	ELECTRON MICROSCOPY	2.9
9FGF	ELECTRON MICROSCOPY	2.9
9FAQ	ELECTRON MICROSCOPY	2.9
9FAW	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28472-F1	80.64	0.63

Antibody-complex structures (SAbDab): 57 — 5O8F, 5OJM, 6A96, 6HUG, 6HUJ, 6HUK, 6HUO, 6HUP, 6I53, 6QFA, 7A5V, 7PBD, 7PBZ, 7PC0, 7QN5, 7QN6, 7QN7, 7QN8, 7QN9, 7QNA, 7QNB, 7QNC, 7QND, 7QNE, 8PET (+32 more)

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 (10): 120–122; 122 (in chain a); 122 (in chain b); 180–182; 180 (in chain a); 181–182 (in chain b); 182 (in chain a); 225; 227 (in chain a); 227 (in chain b)

Disulfide bonds (1): 161–175

Glycosylation sites (3): 33, 105, 174

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1236394	Signaling by ERBB4
R-HSA-977443	GABA receptor activation

MSigDB gene sets: 430 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_CIRCADIAN_RHYTHM, GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, E2F_Q4, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_COGNITION, GOBP_RESPONSE_TO_ZINC_ION, MODULE_274, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_BEHAVIOR, E2F4DP1_01

GO Biological Process (30): signal transduction (GO:0007165), gamma-aminobutyric acid signaling pathway (GO:0007214), learning (GO:0007612), memory (GO:0007613), response to xenobiotic stimulus (GO:0009410), reproductive behavior (GO:0019098), cerebellum development (GO:0021549), social behavior (GO:0035176), exploration behavior (GO:0035640), circadian sleep/wake cycle, REM sleep (GO:0042747), synaptic transmission, GABAergic (GO:0051932), roof of mouth development (GO:0060021), hard palate development (GO:0060022), inhibitory postsynaptic potential (GO:0060080), inner ear receptor cell development (GO:0060119), innervation (GO:0060384), motor behavior (GO:0061744), cellular response to zinc ion (GO:0071294), cellular response to histamine (GO:0071420), response to anesthetic (GO:0072347), cochlea development (GO:0090102), chloride transmembrane transport (GO:1902476), inhibitory synapse assembly (GO:1904862), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), chemical synaptic transmission (GO:0007268), nervous system development (GO:0007399), brain development (GO:0007420), monoatomic ion transmembrane transport (GO:0034220), neuron development (GO:0048666)

GO Molecular Function (9): GABA-A receptor activity (GO:0004890), GABA-gated chloride ion channel activity (GO:0022851), identical protein binding (GO:0042802), 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), signaling receptor activity (GO:0038023)

GO Cellular Component (12): plasma membrane (GO:0005886), cell surface (GO:0009986), cytoplasmic vesicle membrane (GO:0030659), chloride channel complex (GO:0034707), dendritic spine (GO:0043197), postsynaptic membrane (GO:0045211), GABA-ergic synapse (GO:0098982), postsynaptic specialization membrane (GO:0099634), GABA-A receptor complex (GO:1902711), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	1
Neurotransmitter receptors and postsynaptic signal transmission	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
behavior	4
anatomical structure development	3
GABA receptor activity	2
learning or memory	2
response to chemical	2
regulation of postsynaptic membrane potential	2
transmitter-gated monoatomic ion channel activity	2
cellular anatomical structure	2
postsynapse	2
synaptic membrane	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell-cell signaling	1
multicellular organismal reproductive process	1
metencephalon development	1
biological process involved in intraspecies interaction between organisms	1
circadian sleep/wake cycle process	1
circadian sleep/wake cycle, sleep	1
chemical synaptic transmission	1
secondary palate development	1
chemical synaptic transmission, postsynaptic	1
neuron development	1
inner ear receptor cell differentiation	1
nerve development	1
multicellular organismal process	1
response to zinc ion	1
cellular response to metal ion	1
response to histamine	1
cellular response to nitrogen compound	1
chloride channel activity	1
ligand-gated monoatomic anion channel activity	1
protein binding	1
signaling receptor activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
ligand-gated monoatomic ion channel activity	1
monoatomic anion channel activity	1

Protein interactions and networks

STRING

1922 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRB3	UBE3A	P78355	867
GABRB3	SNRPN	P14648	845
GABRB3	ATP10A	O60312	825
GABRB3	GAD1	Q99259	792
GABRB3	MECP2	P51608	779
GABRB3	MKRN3	Q13064	746
GABRB3	SHANK3	Q9BYB0	746
GABRB3	GABBR2	O75899	724
GABRB3	CDKL5	O76039	707
GABRB3	NDN	Q99608	705
GABRB3	CLCN2	P51788	686
GABRB3	CACNA1H	O95180	671
GABRB3	GRIA2	P42262	634
GABRB3	GAD2	Q05329	634
GABRB3	SCN1A	P35498	632

IntAct

28 interactions, top by confidence:

A	B	Type	Score
GABRB3	GABRB3	psi-mi:“MI:0407”(direct interaction)	0.620
GABRA1	GABRG2	psi-mi:“MI:0915”(physical association)	0.550
MCOLN3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
	GABRA1	psi-mi:“MI:0915”(physical association)	0.400
	GABRG2	psi-mi:“MI:0915”(physical association)	0.400
GABRB3	MEOX2	psi-mi:“MI:0915”(physical association)	0.370
GABRB3	GABRA5	psi-mi:“MI:0407”(direct interaction)	0.360
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNB4	GPR89A	psi-mi:“MI:0914”(association)	0.350
GLRA3	GCNT3	psi-mi:“MI:0914”(association)	0.350
GABRA6	HMGCR	psi-mi:“MI:0914”(association)	0.350
GABRB2	GABRB3	psi-mi:“MI:0914”(association)	0.350
GABRA4	GABRG2	psi-mi:“MI:0915”(physical association)	0.320
GABRA4	GABRD	psi-mi:“MI:0915”(physical association)	0.320
GABRB3	GABRG2	psi-mi:“MI:0915”(physical association)	0.320
GABRB3	GABRD	psi-mi:“MI:0915”(physical association)	0.320
Arfgef2	GABRA1	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (22): GABRB3 (Affinity Capture-MS), GABRB3 (Affinity Capture-MS), GABRB3 (Affinity Capture-MS), GABRB3 (Affinity Capture-MS), GABRB3 (Affinity Capture-MS), AKAP5 (Reconstituted Complex), AKAP5 (Affinity Capture-Western), PRKCA (Reconstituted Complex), PRKACA (Reconstituted Complex), GABRB3 (Affinity Capture-RNA), GABRB3 (Affinity Capture-MS), GABRB3 (Affinity Capture-MS), GABRB3 (Affinity Capture-MS), GABRB3 (Affinity Capture-MS), GABRB3 (Affinity Capture-MS)

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: A0A1S4H2E2, A8MPY1, D1LYT2, G5EBR3, O14764, O75311, O93430, P0C2W5, P15431, P18505, P18506, P19019, P20781, P22771, P22933, P23416, P24045, P25123, P28472, P47870, P48167, P48168, P63079, P63080, P63137, P63138, Q08832, Q61603, Q75NA5, Q7TNC8, Q94900, Q9BLY8, Q9GJS9, Q9V9Y4, F1R8P4, O00591, O09028, O18276, P07727, P08219

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GABRB3	“form complex”	“GABA-A (a4-b3-d) receptor”	binding
GABRB3	“form complex”	“GABA-A (a6-b3-d) receptor”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
GABA receptor activation	6	135.9×	5e-11

GO biological processes:

GO term	Partners	Fold	FDR
gamma-aminobutyric acid signaling pathway	7	237.8×	2e-14
inhibitory synapse assembly	6	234.1×	2e-12
synaptic transmission, GABAergic	7	216.8×	2e-14
chloride transmembrane transport	8	118.7×	2e-14

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	47
Likely pathogenic	46
Uncertain significance	311
Likely benign	260
Benign	51

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069296	NM_000814.6(GABRB3):c.288G>T (p.Arg96Ser)	Pathogenic
1069675	NC_000015.9:g.(?26792940)(27020442_?)del	Pathogenic
1164045	NM_000814.6(GABRB3):c.675C>G (p.Phe225Leu)	Pathogenic
1315905	NM_000814.6(GABRB3):c.240+2T>C	Pathogenic
1364700	NM_000814.6(GABRB3):c.923T>G (p.Met308Arg)	Pathogenic
1452714	NM_000814.6(GABRB3):c.374del (p.Asn125fs)	Pathogenic
1453717	NM_000814.6(GABRB3):c.860C>T (p.Thr287Ile)	Pathogenic
1456555	NM_000814.6(GABRB3):c.405_406del (p.Val136fs)	Pathogenic
1460165	NM_000814.6(GABRB3):c.470C>T (p.Thr157Met)	Pathogenic
153815	GRCh38/hg38 15q11.2-13.1(chr15:23328044-28315123)x1	Pathogenic
1723205	NM_000814.6(GABRB3):c.580C>T (p.Arg194Ter)	Pathogenic
2003106	NM_000814.6(GABRB3):c.6G>A (p.Trp2Ter)	Pathogenic
2423402	NC_000015.9:g.(?26866441)(26866701_?)del	Pathogenic
2500725	NM_000814.6(GABRB3):c.929T>G (p.Leu310Arg)	Pathogenic
254262	NM_000814.6(GABRB3):c.545A>T (p.Tyr182Phe)	Pathogenic
254263	NM_000814.6(GABRB3):c.745C>A (p.Gln249Lys)	Pathogenic
254264	NM_000814.6(GABRB3):c.913G>A (p.Ala305Thr)	Pathogenic
2921785	NM_000814.6(GABRB3):c.927C>A (p.Tyr309Ter)	Pathogenic
2947142	NM_000814.6(GABRB3):c.987C>G (p.Tyr329Ter)	Pathogenic
2947221	NM_000814.6(GABRB3):c.817G>A (p.Ala273Thr)	Pathogenic
2949842	NM_000814.6(GABRB3):c.238A>C (p.Met80Leu)	Pathogenic
3243811	NC_000015.9:g.(?26792940)(27018109_?)del	Pathogenic
3243812	NC_000015.9:g.(?27017529)(27018109_?)del	Pathogenic
3243813	NC_000015.9:g.(?26792940)(26866701_?)del	Pathogenic
3243815	NC_000015.9:g.(?26792940)(26828581_?)del	Pathogenic
3251936	NM_000814.6(GABRB3):c.76C>T (p.Gln26Ter)	Pathogenic
3340580	NM_000814.6(GABRB3):c.550T>C (p.Tyr184His)	Pathogenic
3342557	NM_021912.5(GABRB3):c.39G>A (p.Trp13Ter)	Pathogenic
3384351	NM_000814.6(GABRB3):c.229G>A (p.Glu77Lys)	Pathogenic
3391509	NM_000814.6(GABRB3):c.239T>A (p.Met80Lys)	Pathogenic

SpliceAI

4460 predictions. Top by Δscore:

Variant	Effect	Δscore
15:26561174:TCC:T	acceptor_gain	1.0000
15:26561174:TCCCT:T	acceptor_loss	1.0000
15:26561175:CC:C	acceptor_gain	1.0000
15:26561175:CCC:C	acceptor_gain	1.0000
15:26561176:CC:C	acceptor_gain	1.0000
15:26561176:CCTAG:C	acceptor_loss	1.0000
15:26561177:C:CC	acceptor_gain	1.0000
15:26561177:CTA:C	acceptor_loss	1.0000
15:26561178:T:A	acceptor_loss	1.0000
15:26567575:ACAT:A	donor_loss	1.0000
15:26567576:CATA:C	donor_loss	1.0000
15:26567577:ATAC:A	donor_loss	1.0000
15:26567578:TA:T	donor_loss	1.0000
15:26567579:A:AC	donor_gain	1.0000
15:26567580:C:CC	donor_gain	1.0000
15:26567734:C:CC	acceptor_gain	1.0000
15:26580314:CTCA:C	donor_loss	1.0000
15:26580315:TCACC:T	donor_loss	1.0000
15:26580316:CA:C	donor_loss	1.0000
15:26580317:ACCTG:A	donor_loss	1.0000
15:26580318:C:T	donor_loss	1.0000
15:26580452:GCCAT:G	acceptor_gain	1.0000
15:26580453:CCAT:C	acceptor_gain	1.0000
15:26580453:CCATC:C	acceptor_gain	1.0000
15:26580454:CAT:C	acceptor_gain	1.0000
15:26580454:CATC:C	acceptor_gain	1.0000
15:26580455:AT:A	acceptor_gain	1.0000
15:26580455:ATCT:A	acceptor_loss	1.0000
15:26580456:TCTG:T	acceptor_loss	1.0000
15:26580457:C:CC	acceptor_gain	1.0000

AlphaMissense

3106 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:26547869:T:A	D449V	1.000
15:26547869:T:G	D449A	1.000
15:26547870:C:G	D449H	1.000
15:26561028:G:C	N328K	1.000
15:26561028:G:T	N328K	1.000
15:26561038:G:T	A325D	1.000
15:26561042:A:G	Y324H	1.000
15:26561047:A:G	L322P	1.000
15:26561050:A:G	L321P	1.000
15:26561050:A:T	L321H	1.000
15:26561053:G:T	A320D	1.000
15:26561058:G:C	F318L	1.000
15:26561058:G:T	F318L	1.000
15:26561060:A:G	F318L	1.000
15:26561075:A:G	C313R	1.000
15:26561083:A:G	L310P	1.000
15:26561092:T:A	D307V	1.000
15:26561092:T:G	D307A	1.000
15:26561093:C:G	D307H	1.000
15:26561100:T:A	K304N	1.000
15:26561100:T:G	K304N	1.000
15:26561119:G:T	P298H	1.000
15:26561158:G:T	T285K	1.000
15:26561161:A:C	L284R	1.000
15:26561161:A:G	L284P	1.000
15:26561161:A:T	L284Q	1.000
15:26561164:A:T	V283E	1.000
15:26561176:C:T	G279E	1.000
15:26567581:C:A	G279W	1.000
15:26567581:C:G	G279R	1.000

dbSNP variants (sampled 300 via entrez): RS1000004673 (15:26546511 G>A), RS1000009059 (15:26630226 A>G), RS1000016919 (15:26552325 C>T), RS1000023925 (15:26676934 C>A), RS1000026523 (15:26733141 T>A), RS1000033739 (15:26632204 C>A,T), RS1000055841 (15:26670537 A>T), RS1000056365 (15:26732853 C>A), RS1000060223 (15:26579618 T>C), RS1000077152 (15:26591454 T>A), RS1000122231 (15:26580171 A>G), RS1000133990 (15:26695082 T>C), RS1000140318 (15:26770086 C>A,G,T), RS1000158007 (15:26672119 A>C), RS1000192968 (15:26693139 C>A,T)

Disease associations

OMIM: gene MIM:137192 | disease phenotypes: MIM:612269, MIM:617113, MIM:600131, MIM:181500, MIM:308350

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 43	Definitive	Autosomal dominant
genetic developmental and epileptic encephalopathy	Definitive	Autosomal dominant
epilepsy, childhood absence, susceptibility to, 5	Definitive	Autosomal dominant
Lennox-Gastaut syndrome	Supportive	Autosomal dominant
childhood absence epilepsy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Definitive	AD

Mondo (12): epilepsy, childhood absence, susceptibility to, 5 (MONDO:0012843), developmental and epileptic encephalopathy, 43 (MONDO:0014921), epilepsy, childhood absence, susceptibility to, 1 (MONDO:0020759), insomnia (MONDO:0013600), schizophrenia (MONDO:0005090), myoepithelial tumor (MONDO:0002380), epilepsy (MONDO:0005027), intellectual disability (MONDO:0001071), developmental and epileptic encephalopathy, 1 (MONDO:0010632), genetic developmental and epileptic encephalopathy (MONDO:0100062), Lennox-Gastaut syndrome (MONDO:0016532), childhood absence epilepsy (MONDO:0010826)

Orphanet (3): Childhood absence epilepsy (Orphanet:64280), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

58 total (30 of 58 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000737	Irritability
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000752	Hyperactivity
HP:0000980	Pallor
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001328	Specific learning disability
HP:0001336	Myoclonus
HP:0002069	Bilateral tonic-clonic seizure
HP:0002121	Generalized non-motor (absence) seizure
HP:0002123	Generalized myoclonic seizure
HP:0002321	Vertigo
HP:0002353	EEG abnormality
HP:0002360	Sleep disturbance
HP:0002363	Abnormal brainstem morphology
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002376	Developmental regression
HP:0002521	Hypsarrhythmia

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000477_24	Cognitive performance	2.000000e-06
GCST000785_3	Longevity	1.000000e-06
GCST002408_14	Response to methotrexate in juvenile idiopathic arthritis	3.000000e-06
GCST004904_176	Body mass index	3.000000e-08
GCST008170_3	Thyroglobulin plasma levels	2.000000e-06
GCST008181_11	Spontaneous preterm birth without premature rupture of membranes	5.000000e-06
GCST009196_7	Pericalcarine cortex volume	7.000000e-06
GCST010002_162	Refractive error	4.000000e-11
GCST010396_211	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-06
GCST011050_4	Postprandial triglyceride response	3.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0004340	body mass index
EFO:0010050	thyroglobulin measurement
EFO:0006917	spontaneous preterm birth
EFO:0007874	gut microbiome measurement
EFO:0004530	triglyceride measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065768	Lennox Gastaut Syndrome	C10.228.140.490.493.750; C16.320.495
D009208	Myoepithelioma	C04.557.435.585
D007319	Sleep Initiation and Maintenance Disorders	C10.886.425.800.800; F03.870.400.800.800

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (19): CHEMBL1847 (SINGLE PROTEIN), CHEMBL2093872 (PROTEIN COMPLEX GROUP), CHEMBL2094120 (PROTEIN COMPLEX), CHEMBL2094121 (PROTEIN COMPLEX), CHEMBL2094122 (PROTEIN COMPLEX), CHEMBL2094130 (PROTEIN COMPLEX), CHEMBL2095190 (PROTEIN COMPLEX), CHEMBL2109244 (PROTEIN COMPLEX GROUP), CHEMBL2111366 (PROTEIN COMPLEX), CHEMBL3430899 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

32 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 527,705 (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
CHEMBL15891	LINDANE	4	83,653
CHEMBL448	PENTOBARBITAL	4	49,933
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
CHEMBL451	CHLORDIAZEPOXIDE	4	36,533
CHEMBL646	TRIAZOLAM	4	21,589
CHEMBL911	ZOLPIDEM	4	17,821
CHEMBL526	PROPOFOL	4	28,835
CHEMBL1521	ZALEPLON	4	9,958
CHEMBL4105630	ZURANOLONE	4	290
CHEMBL268254	DELORAZEPAM	2	1,308
CHEMBL275638	FLAVONE	2	88,985
CHEMBL287631	PROGABIDE	2	3,853
CHEMBL454095	ABECARNIL	2
CHEMBL8260	BAICALEIN	2
CHEMBL200177	MK-0777	2
CHEMBL3647536	DARIGABAT	2
CHEMBL366947	BRETAZENIL	2
CHEMBL1397886	LORECLEZOLE	2
CHEMBL190279	ALFAXALONE	2
CHEMBL3681419	BASMISANIL	2
CHEMBL1783282	AZD7325	2
CHEMBL273481	MUSCIMOL	1

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4906902	Toxicity	3	opioids	Opioid-Related Disorders

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4906902	GABRB3	3	2.00	1	opioids

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
etazolate	Binding	5.46	pIC50

Binding affinities (BindingDB)

369 measured of 380 human assays (381 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-5,6-dihydropyridin-2(1H)-one	KI	0.27 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
(R)-8-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)hexahydro-2H-pyrazino[1,2-a]pyrazin-1(6H)-one	KI	0.39 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-((1-(5-Chloropyridin-2-yl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)piperazin-2-one	KI	0.46 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-[5-[[3-[4-(difluoromethyl)phenyl]-5-methyltriazol-4-yl]methoxy]pyrido[2,3-d]pyridazin-8-yl]piperazin-2-one	KI	0.49 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
1-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)imidazolidin-2-one	KI	0.52 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
(S)-8-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-2-fluoro-7,8,9,10-tetrahydro-5H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-6(6aH)-one	KI	0.54 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
(9aR)-8-[6-[[3-[4-(difluoromethyl)phenyl]-5-methyltriazol-4-yl]methoxy]pyridazin-3-yl]-1,3,4,7,9,9a-hexahydropyrazino[2,1-c][1,4]oxazin-6-one	KI	0.55 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-[6-[[3-[4-(difluoromethyl)phenyl]-5-methyltriazol-4-yl]methoxy]-5-methylpyridazin-3-yl]piperazin-2-one	KI	0.56 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-3-methylpiperazin-2-one	KI	0.58 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
7-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine	KI	0.6 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-[6-[[3-[4-(difluoromethyl)phenyl]-5-methyltriazol-4-yl]methoxy]-4-methylpyridazin-3-yl]piperazin-2-one	KI	0.63 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
(S)-8-(5-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyrido[2,3-d]pyridazin-8-yl)hexahydro-2H-pyrazino[1,2-a]pyrazin-1(6H)-one	KI	0.64 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-1-(2-morpholinoethyl)piperazin-2-one	KI	0.67 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
1-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-N-ethyl-1,2,5,6-tetrahydropyridine-3-carboxamide	KI	0.67 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
Halcion	KI	0.68 nM
(9aR)-8-[6-[[5-chloro-3-[4-(difluoromethyl)phenyl]triazol-4-yl]methoxy]pyridazin-3-yl]-1,3,4,7,9,9a-hexahydropyrazino[2,1-c][1,4]oxazin-6-one	KI	0.71 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
3-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)-6-(5,6-dihydro-2H-pyran-3-yl)pyridazine	KI	0.75 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
(S)-8-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-7,8,9,10-tetrahydro-5H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-6(6aH)-one	KI	0.8 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-1-(1-methyl-1H-pyrazol-3-yl)piperazin-2-one	KI	0.81 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-((1-(4-(Difluoromethyl)phenyl)-4-(hydroxymethyl)-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)piperazin-2-one	KI	0.82 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
2-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)hexahydro-1H-pyrazino[1,2-a]pyrazin-4-(6H)-one	KI	0.84 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
1H-2-imidazolyl[6-phenyl-4,5,7,8-tetraazatetracyclo[9.2.2.02,10.03,7]pentadeca-2(10),3,5,8-tetraen-9-yloxy]methane	KI	0.87 nM
7-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-4,7-diazaspiro[2.5]octan-5-one	KI	0.89 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
1-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-N,N-dimethylpyrrolidin-3-amine	KI	0.89 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
2-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-8-methylhexahydro-1H-pyrazino[1,2-a]pyrazin-4(6H)-one	KI	0.9 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-6-methylpiperazin-2-one	KI	0.91 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-1-(1-methyl-1H-pyrazol-4-yl)piperazin-2-one	KI	0.93 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)piperazine-2,6-dione	KI	0.96 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-((4-(Difluoromethyl)-1-(4-(difluoromethyl)phenyl)-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)piperazin-2-one	KI	0.96 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-6,6-dimethylpiperazin-2-one	KI	1 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-[6-[[3-[4-(difluoromethyl)phenyl]-5-methyltriazol-4-yl]methoxy]-4-methoxypyridazin-3-yl]piperazin-2-one	KI	1.05 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
1-(4-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)piperazin-1-yl)ethan-1-one	KI	1.07 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-((1-(4-(Difluoromethyl)-2-fluorophenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)piperazin-2-one	KI	1.08 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
1-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-N-phenylazetidine-3-carboxamide	KI	1.1 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
1-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-N-(pyridin-4-yl)azetidine-3-carboxamide	KI	1.1 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
2-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-8-(pyrimidin-2-ylmethyl)octahydro-4H-pyrazino[1,2-a]pyrazin-4-one	KI	1.1 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
1-(Cyclopropylmethyl)-4-(6-((1-(4-(difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)piperazin-2-one	KI	1.11 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(5-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyrazin-2-yl)piperazin-2-one	KI	1.11 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
2-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-8-(2,2,2-trifluoroethyl)octahydro-4H-pyrazino[1,2-a]pyrazin-4-one	KI	1.13 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
1-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-N-(1-methyl-1H-pyrazol-3-yl)azetidine-3-carboxamide	KI	1.15 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
1-(1-(Difluoromethyl)-1H-pyrazol-4-yl)-4-(6-((1-(4-(difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)piperazin-2-one	KI	1.17 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-1-(2,2,2-trifluoroethyl)piperazin-2-one	KI	1.18 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
2-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)hexahydro-3H-imidazo[5,1-c][1,4]oxazin-3-one	KI	1.19 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
(S)-8-(6-((4-Chloro-1-(4-(difluoromethyl)phenyl)-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)hexahydro-2H-pyrazino[1,2-a]pyrazin-1(6H)-one	KI	1.21 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
(S)-2-(6-((1-(4-(difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)hexahydropyrrolo[1,2-a]pyrazin-4(1H)-one	KI	1.24 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
4-(6-[(1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy]pyridin-3-yl)piperazin-2-one	KI	1.24 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
9-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-6-oxa-2-thia-9-azaspiro[4.5]decane 2,2-dioxide	KI	1.24 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
2-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-N-ethyl-2-azabicyclo[2.1.1]hexane-1-carboxamide	KI	1.25 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
(3S,9aR)-8-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)tetrahydro-1H-3,9a-methanopyrazino[2,1-c][1,4]oxazin-6(7H)-one	KI	1.26 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
1-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-N-(1-methyl-1H-pyrazol-4-yl)azetidine-3-carboxamide	KI	1.27 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF

ChEMBL bioactivities

3874 potent at pChembl≥5 of 4004 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	Ki	0.02	nM	CHEMBL3144696
10.52	Ki	0.03	nM	CHEMBL3144849
10.40	Ki	0.04	nM	CHEMBL3144849
10.30	Ki	0.05	nM	CGS-8216
10.30	Ki	0.05	nM	CHEMBL4243764
10.22	Ki	0.06	nM	CHEMBL3144696
10.22	Ki	0.06	nM	CHEMBL4243764
10.15	Ki	0.07	nM	CHEMBL3144849
10.10	Ki	0.08	nM	CHEMBL3144696
10.10	Ki	0.08	nM	CGS-8216
10.10	Ki	0.08	nM	CHEMBL4243764
10.05	Ki	0.09	nM	CHEMBL3144841
10.00	IC50	0.1	nM	CHEMBL454349
10.00	Ki	0.1	nM	CHEMBL436768
10.00	Ki	0.1	nM	CHEMBL202696
10.00	Ki	0.1	nM	CHEMBL203286
10.00	Ki	0.1	nM	CHEMBL378761
10.00	Ki	0.1	nM	CHEMBL211704
10.00	Ki	0.1	nM	CHEMBL3144841
9.96	Ki	0.11	nM	CHEMBL380110
9.96	Ki	0.11	nM	CHEMBL3144841
9.92	Ki	0.12	nM	CHEMBL199957
9.92	Ki	0.12	nM	CHEMBL4476044
9.92	Ki	0.12	nM	CHEMBL3144615
9.92	Ki	0.12	nM	CGS-8216
9.92	Ki	0.12	nM	CHEMBL4243764
9.85	Ki	0.14	nM	CHEMBL383677
9.85	Ki	0.14	nM	CHEMBL212008
9.85	Ki	0.14	nM	CHEMBL225631
9.85	Ki	0.14	nM	CHEMBL1644826
9.85	Ki	0.14	nM	CHEMBL130609
9.85	Ki	0.14	nM	CHEMBL10483
9.82	Ki	0.15	nM	CHEMBL202343
9.82	Ki	0.15	nM	CHEMBL206587
9.82	Ki	0.15	nM	CHEMBL300615
9.80	IC50	0.16	nM	CHEMBL309517
9.80	Ki	0.16	nM	CHEMBL206380
9.77	Ki	0.17	nM	CHEMBL375742
9.77	Ki	0.17	nM	CHEMBL3144849
9.77	Ki	0.17	nM	CHEMBL3144615
9.77	Ki	0.17	nM	CHEMBL299210
9.74	Ki	0.18	nM	DARIGABAT
9.74	Ki	0.18	nM	CHEMBL323805
9.74	Ki	0.18	nM	CHEMBL3144698
9.72	Ki	0.19	nM	CHEMBL361129
9.72	Ki	0.19	nM	CHEMBL206380
9.72	Ki	0.19	nM	CHEMBL4436326
9.70	Ki	0.2	nM	CHEMBL178677
9.70	Ki	0.2	nM	MK-0777
9.70	Ki	0.2	nM	CHEMBL381380

PubChem BioAssay actives

3443 with measured affinity, of 6100 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-ethynyl-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73244: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-3-beta-3-gamma-2	ki	<0.0001	uM
8-methoxy-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-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
5-fluoro-2-[2-fluoro-5-[7-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]benzonitrile	259132: Displacement of [3H]Ro-151788 from human recombinant GABAA alpha5 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0001	uM
8-chloro-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73244: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-3-beta-3-gamma-2	ki	0.0001	uM
tert-butyl 8-hydroxy-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	ki	0.0001	uM
3-phenyl-6-(pyridazin-3-ylmethoxy)-[1,2,4]triazolo[3,4-a]phthalazine	72625: Binding affinity for human GABA-A receptor alpha-5-beta-3-gamma-2 subunits in L(tk-) cells	ki	0.0001	uM
2-[5-(7-ethyl-8-oxoimidazo[1,2-a]pyrazin-3-yl)-2-fluorophenyl]-5-fluorobenzonitrile	262297: Displacement of [3H]Ro-151788 from human recombinant GABA-Aalpha5 receptor plus beta3gamma2	ki	0.0001	uM
3,5-difluoro-2-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile	260334: Displacement of [3H]Ro 15-1788 from recombinant human GABAA alpha-1 receptor plus beta3gamma2 expressed in L(tk-) cells	ki	0.0001	uM
7-tert-butyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine	282667: Displacement of [3H]Ro 15-1788 from human recombinant GABAA alpha-3-beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
3-(2,6-difluorophenyl)-5-[4-fluoro-3-(3-fluoro-2-pyridinyl)phenyl]pyridazine	262644: Displacement of [3H]Ro-151788 from recombinant human GABA-Aalpha1 receptor plus beta3gamma2	ki	0.0001	uM
ethyl 6-methoxy-4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate	219791: Binding affinity measured using LtK- cell membranes expressing GABA alpha-1-beta-3-gamma-2 receptor	ki	0.0001	uM
2-(4-methylphenyl)-9-(2-thiophen-3-ylethyl)-6H-[1,2,4]triazolo[4,3-c]quinazoline-3,5-dione	552801: Displacement of [3H]flumazenil human recombinant alpha1beta3gamma2 GABA(A) receptor expressed in HEK293 cells after 30 mins by glass fiber filtration assay	ki	0.0001	uM
7-(2-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-thiophen-3-ylpyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
2-[3-[5-(2-hydroxypropan-2-yl)benzimidazol-1-yl]phenyl]benzonitrile	1604549: Displacement of [3H]-Ro15-1788 from human GABAA alpha5beta3gamma2 expressed in HEK293 cell membranes incubated for 40 or 90 mins by liquid scintillation counting method	ki	0.0001	uM
7-(2-fluorophenyl)-3-(furan-2-yl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]pyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
7-(2-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-thiophen-2-ylpyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
2-phenyl-3aH-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	ki	0.0001	uM
8-bromo-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	ki	0.0001	uM
4-[2-fluoro-5-[7-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]pyridine-3-carbonitrile	262147: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha5 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0001	uM
7-(2-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-pyridin-4-ylpyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
2-[2-fluoro-5-[8-fluoro-7-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]benzonitrile	262219: Displacement of [3H]Ro 15-1788 from human GABA-Aalpha1 receptor plus beta-3-gamma-2 expressed in mouse L(tk-) cells	ki	0.0002	uM
8-chloro-2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	1388015: Displacement of [3H]Ro15-1788 from human GABAA receptor alpha1beta3gamma2 expressed in LTK cells preincubated for 30 secs measured every 15 mins at -60 mV holding potential by two-electrode voltage clamp assay	ki	0.0002	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	73244: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-3-beta-3-gamma-2	ki	0.0002	uM
6-phenyl-9-[(2-propyl-1,2,4-triazol-3-yl)methoxy]-4,5,7,8-tetrazatetracyclo[9.2.2.02,10.03,7]pentadeca-2(10),3,5,8-tetraene	239566: Inhibition of [3H]Ro-151788 binding to recombinant human gamma-aminobutyric-acid A receptor alpha-5-beta-3-gamma-2 subtype expressed in L (tk-) cells	ki	0.0002	uM
9-[(1-benzylimidazol-2-yl)methoxy]-6-phenyl-4,5,7,8-tetrazatetracyclo[9.2.2.02,10.03,7]pentadeca-2(10),3,5,8-tetraene	239566: Inhibition of [3H]Ro-151788 binding to recombinant human gamma-aminobutyric-acid A receptor alpha-5-beta-3-gamma-2 subtype expressed in L (tk-) cells	ki	0.0002	uM
6-[(1-methylimidazol-2-yl)methoxy]-3-phenyl-[1,2,4]triazolo[3,4-a]phthalazine	72620: Binding affinity for human GABA-A receptor alpha-3-beta-3-gamma-2 subunits in L(tk-) cells	ki	0.0002	uM
9-[(3,5-dimethyl-2-pyridinyl)methoxy]-6-phenyl-4,5,7,8-tetrazatetracyclo[9.2.2.02,10.03,7]pentadeca-2(10),3,5,8-tetraene	239566: Inhibition of [3H]Ro-151788 binding to recombinant human gamma-aminobutyric-acid A receptor alpha-5-beta-3-gamma-2 subtype expressed in L (tk-) cells	ki	0.0002	uM
ethyl 15-methoxy-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carboxylate	448426: Binding affinity to GABAA alpha-5-beta-3-gamma-2 receptor	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-chlorophenyl)-6,7,8,9-tetrahydro-1H-pyrazolo[4,3-c]quinolin-3-one	221780: In vitro binding affinity against gamma-aminobutyric acid A receptor, alpha 1 expressed in L(tk) cells by displacement of [3H]Ro-151788	ki	0.0002	uM
2-(4-bromophenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	ki	0.0002	uM
3-(2,5-difluorophenyl)-7-(2-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]pyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0002	uM
3-(15-fluoro-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaen-5-yl)-5-methyl-1,2,4-oxadiazole	468635: Displacement of [3H]Flumazenil from cloned human GABA alpha-5-beta-3-gamma-2 receptor expressed in HEK293 cells	ki	0.0002	uM
ethyl 2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(17),3,5,9,11,13,15-heptaene-5-carboxylate	448426: Binding affinity to GABAA alpha-5-beta-3-gamma-2 receptor	ki	0.0002	uM
ethyl 15-chloro-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carboxylate	448426: Binding affinity to GABAA alpha-5-beta-3-gamma-2 receptor	ki	0.0002	uM
ethyl 15-fluoro-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carboxylate	468641: Displacement of [3H]Flumazenil from human GABA alpha-5-beta-3-gamma-2 receptor expressed in insect SF9 cells	ki	0.0002	uM
7-cyclobutyl-3-(2,6-difluorophenyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine	1604538: Displacement of [3H]-flumazenil from human GABAA alpha1beta3gamma2 expressed in Ltk cells	ki	0.0002	uM
15-(4-chlorophenyl)-13-(4-methyl-1,3-thiazol-2-yl)-4,11-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2(7),3,5,13-pentaen-12-one	72914: Displacement of [3H]Ro-151788 from human GABA-A receptor alpha-1-beta-3-gamma-2 subunits expressed in L(tk) cells	ki	0.0002	uM
2-(4-chlorophenyl)-8-(pyridin-4-ylmethyl)-1,5a,6,7,9,9a-hexahydropyrazolo[4,3-c][1,6]naphthyridin-3-one	221780: In vitro binding affinity against gamma-aminobutyric acid A receptor, alpha 1 expressed in L(tk) cells by displacement of [3H]Ro-151788	ki	0.0002	uM
3-fluoro-2-[2-fluoro-5-(7-methyl-8-oxoimidazo[1,2-a]pyrazin-3-yl)phenyl]benzonitrile	262295: Displacement of [3H]Ro-151788 from human recombinant GABA-Aalpha1 receptor plus beta3gamma2	ki	0.0002	uM
5-ethoxy-2,4,8,9-tetrazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(17),3,5,9,11,13,15-heptaene	448426: Binding affinity to GABAA alpha-5-beta-3-gamma-2 receptor	ki	0.0002	uM
7-ethyl-4-[3-(4-ethylsulfonyl-2-methoxyphenyl)-4-fluorophenyl]imidazo[4,5-c]pyridazine	1553920: Displacement of [3H]-flumazenil from human GABAA alpha1beta3gamma2 receptor expressed in HEK293 cell membranes measured after 2 hrs by liquid scintillation counting method	ki	0.0002	uM
4-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]pyridine-3-carbonitrile	262147: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha5 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0003	uM
4-fluoro-2-[2-fluoro-5-[7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]benzonitrile	259132: Displacement of [3H]Ro-151788 from human recombinant GABAA alpha5 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0003	uM
2-[3-(4-fluoro-3-pyridin-4-ylphenyl)imidazo[1,2-a]pyrimidin-7-yl]propan-2-ol	262147: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha5 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0003	uM
7-methoxy-2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	ki	0.0003	uM
tert-butyl 8-azido-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	ki	0.0003	uM
ethyl (7S)-14-bromo-11-oxo-2,4,10-triazatetracyclo[10.4.0.02,6.07,10]hexadeca-1(16),3,5,12,14-pentaene-5-carboxylate	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	ki	0.0003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	8
gamma-Aminobutyric Acid	affects binding, increases activity, increases reaction, affects cotreatment, decreases reaction (+1 more)	6
methylmercuric chloride	increases expression, affects cotreatment	4
fipronil	decreases activity, affects binding, decreases reaction	4
1-(4-ethynylphenyl)-4-propyl-2,6,7-trioxabicyclo(2.2.2)octane	affects binding, decreases activity, decreases reaction, increases reaction	4
Hexachlorocyclohexane	affects binding, decreases reaction, increases activity, increases reaction	4
trichostatin A	affects cotreatment, increases expression	3
loreclezole	increases transport, affects binding, affects cotreatment, increases activity, increases reaction (+1 more)	3
Endosulfan	decreases reaction, affects binding	3
Propofol	affects cotreatment, affects binding, decreases reaction, increases activity, increases reaction (+1 more)	3
picrotoxinin	affects binding, decreases reaction, increases activity, increases response to substance	2
tert-butylbicyclophosphorothionate	affects binding, decreases reaction	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	affects cotreatment, decreases expression, increases expression	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	decreases expression, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Flunitrazepam	affects binding, increases reaction, increases activity, affects reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	affects methylation, decreases expression, increases methylation	2
4-chloro-N-(2-(2-thienyl)imidazo(1,2-a)pyridin-3-yl)benzamide	affects binding, increases activity	1
bisphenol A	affects cotreatment, decreases methylation	1
tetramethylenedisulfotetramine	increases response to substance, affects binding, decreases reaction, increases activity	1
sodium arsenite	affects methylation	1
butyraldehyde	decreases expression	1
CL 218872	affects binding, increases activity	1
benzamide	increases reaction, affects binding, increases activity	1
alpha-hexachlorocyclohexane	increases reaction, affects binding, decreases reaction, increases activity	1
Ro 15-4513	affects binding, increases activity, increases reaction	1

ChEMBL screening assays

887 unique, capped per target: 722 binding, 156 functional, 6 admet, 3 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2167730	Binding	Inhibition of [3H]R-(-)-14-induced receptor photolabeling at human FLAG-tagged beta3 GABA A receptor expressed in HEK293S cells at 200 uM relative to untreated control	Allyl m-trifluoromethyldiazirine mephobarbital: an unusually potent enantioselective and photoreactive barbiturate general anesthetic. — J Med Chem
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

8 cell lines: 6 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1JK	PrecisION hGABAA alpha1/beta3/gamma2-HEK	Transformed cell line	Female
CVCL_D1JL	PrecisION hGABAA alpha3/beta3/gamma2-HEK	Transformed cell line	Female
CVCL_D1JM	PrecisION hGABAA alpha4/beta3/gamma2-HEK	Transformed cell line	Female
CVCL_D1JN	PrecisION hGABAA alpha5/beta3/gamma2-HEK	Transformed cell line	Female
CVCL_D1JP	PrecisION hGABAA alpha6/beta3/gamma2-HEK	Transformed cell line	Female
CVCL_D1KP	PrecisION hGABAA alpha2/beta3/gamma2-HEK	Transformed cell line	Female
CVCL_SP45	HAP1 GABRB3 (-) 1	Cancer cell line	Male
CVCL_SP46	HAP1 GABRB3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01370486	PHASE4	WITHDRAWN	Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects
NCT02731300	PHASE4	COMPLETED	Transcranial Direct Current Stimulation, Treatment of Childhood Drug-Resistant Lennox-Gastaut Syndrome, A Pilot Study
NCT04133480	PHASE4	WITHDRAWN	Investigation of Cognitive Outcomes With Cannabidiol Oral Solution
NCT05044819	PHASE4	ACTIVE_NOT_RECRUITING	Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution
NCT06924827	PHASE4	NOT_YET_RECRUITING	A Study to Investigate the Transition of Children From ‘Artisanal Cannabidiol (CBD) to Epidiolex
NCT00124384	PHASE4	COMPLETED	The Effects of Modafinil on Waking Function and on Sleep in Individuals With Primary Insomnia
NCT00156533	PHASE4	COMPLETED	Long Term Treatment With Zolpidem: Nightly and Intermittent Dosing
NCT00178048	PHASE4	COMPLETED	Paroxetine in the Treatment of Chronic Primary Insomnia
NCT00235508	PHASE4	COMPLETED	Safety and Efficacy of Eszopiclone in Patients With Generalized Anxiety Disorder
NCT00252278	PHASE4	UNKNOWN	Effect of Atomoxetine on ADHD-Related Insomnia in Children and Adolescents
NCT00283790	PHASE4	COMPLETED	Residual Effects of Zolpidem Tartrate Extended Release and Eszopiclone Vs Placebo
NCT00287391	PHASE4	COMPLETED	Sleep Disorders and Gastroesophageal Reflux Disease (GERD)
NCT00295386	PHASE4	COMPLETED	Cognitive-Behavioural and Hypnotic Treatment of Chronic Primary Insomnia Among the Elderly
NCT00296179	PHASE4	COMPLETED	Ambien CR For Treatment Of Insomnia Associated With Depression When Used Concomitantly With Lexapro
NCT00296790	PHASE4	COMPLETED	Ambien CR vs. Placebo For Treatment Of Insomnia Associated With Anxiety When Used Concomitantly With Escitalopram (Lexapro)
NCT00337272	PHASE4	TERMINATED	Treating Chronic Insomnia in Breast Cancer Patients
NCT00359229	PHASE4	COMPLETED	Stilnox Treatment in Elderly Patients With Insomnia
NCT00365976	PHASE4	COMPLETED	Study of the Insomnia in Patients With Low Back Pain
NCT00386334	PHASE4	COMPLETED	A Long-Term Safety and Efficacy Study of Eszopiclone in Elderly With Primary Chronic Insomnia
NCT00392041	PHASE4	COMPLETED	Eszopiclone in the Treatment of Insomnia and Fibromyalgia
NCT00414037	PHASE4	TERMINATED	How do Sleeping Pills Affect Pain in the Brain?
NCT00414102	PHASE4	COMPLETED	Subjective Efficacy of Ramelteon on Sleep in Adults With Chronic Insomnia.
NCT00432198	PHASE4	COMPLETED	Zolpidem Postmarketing Study in Adolescent Patients With Insomnia
NCT00465972	PHASE4	COMPLETED	The Treatment of Insomnia in Patients With HIV Disease
NCT00492232	PHASE4	COMPLETED	Facilitation of Zolpidem (≥10 mg) Discontinuation Through Use of Ramelteon in Subjects With Chronic Insomnia
NCT00507546	PHASE4	COMPLETED	Functional Melatonin Replacement for Sleep Disruptions in Individuals With Tetraplegia
NCT00511134	PHASE4	TERMINATED	Study of Lunesta Versus Placebo for Sleep Problems Related to Smoking Cessation and Zyban
NCT00566371	PHASE4	COMPLETED	The Effect of a Once Daily Dose of Atomoxetine (ATX) on ADHD-Related Insomnia in Children and Adolescents
NCT00568789	PHASE4	COMPLETED	Safety of Ramelteon in Elderly Subjects
NCT00626210	PHASE4	TERMINATED	Modafinil Treatment for Sleep/Wake Disturbances in Older Adults
NCT00628914	PHASE4	UNKNOWN	Brain Mechanisms and Targeting Insomnia in Major Depression
NCT00653562	PHASE4	COMPLETED	Zolpidem (Myslee) Post Marketing Study in Adolescent Patients With Insomnia - Evaluation With Polysomnography
NCT00666796	PHASE4	COMPLETED	A Study to Assess the Pharmacodynamic Interaction Between Gabapentin and Ethanol in Healthy Subjects
NCT00723970	PHASE4	COMPLETED	Quetiapine Extended Release (XR) for the Treatment of Menopausal Depression
NCT00724282	PHASE4	COMPLETED	Treatment of Insomnia and Glucose Metabolism
NCT00812214	PHASE4	COMPLETED	Treatment of Insomnia in Migraineurs
NCT00813735	PHASE4	COMPLETED	Eszopiclone Co-Administered With Escitalopram for Insomnia in Elderly Adults With Major Depressive Disorder
NCT00826111	PHASE4	COMPLETED	The Effects of Eszopiclone and Lexapro on Prefrontal Glutamate and GABA in Depression With Anxiety and Insomnia
NCT00869934	PHASE4	COMPLETED	Cognitive-Behavior Therapy for Insomnia
NCT00889200	PHASE4	COMPLETED	Eszopiclone Treatment & Cortisol Responsivity