GABRG2

Summary

GABRG2 (gamma-aminobutyric acid type A receptor subunit gamma2, HGNC:4087) is a protein-coding gene on chromosome 5q34, encoding Gamma-aminobutyric acid receptor subunit gamma-2 (P18507). Gamma 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 gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammlian brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene have been associated with epilepsy and febrile seizures. Multiple transcript variants encoding different isoforms have been identified for this gene.

Source: NCBI Gene 2566 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epilepsy (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 796 total — 84 pathogenic, 52 likely-pathogenic
• Phenotypes (HPO): 143
• Druggable target: yes — 55 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_198904

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4087
Approved symbol	GABRG2
Name	gamma-aminobutyric acid type A receptor subunit gamma2
Location	5q34
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000113327
Ensembl biotype	protein_coding
OMIM	137164
Entrez	2566

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 18 protein_coding, 6 nonsense_mediated_decay, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000356592, ENST00000361925, ENST00000414552, ENST00000522053, ENST00000522990, ENST00000523372, ENST00000638253, ENST00000638552, ENST00000638660, ENST00000638772, ENST00000638782, ENST00000638877, ENST00000639046, ENST00000639111, ENST00000639213, ENST00000639278, ENST00000639384, ENST00000639424, ENST00000639549, ENST00000639554, ENST00000639683, ENST00000639975, ENST00000640500, ENST00000640574, ENST00000640739, ENST00000640757, ENST00000640910, ENST00000640985, ENST00000641017, ENST00000943443, ENST00000943444

RefSeq mRNA: 15 — MANE Select: NM_198904 NM_000816, NM_001375339, NM_001375340, NM_001375341, NM_001375342, NM_001375343, NM_001375344, NM_001375345, NM_001375346, NM_001375347, NM_001375348, NM_001375349, NM_001375350, NM_198903, NM_198904

CCDS: CCDS4358, CCDS4359, CCDS47333, CCDS93812, CCDS93813, CCDS93814, CCDS93815, CCDS93816

Canonical transcript exons

ENST00000639213 — 10 exons

Exon	Start	End
ENSE00001422058	162151730	162151753
ENSE00003477526	162095495	162095562
ENSE00003477712	162149108	162149313
ENSE00003535086	162097638	162097858
ENSE00003536104	162101235	162101317
ENSE00003610094	162142164	162142316
ENSE00003625954	162103889	162104026
ENSE00003654309	162093828	162093979
ENSE00003809373	162153093	162155526
ENSE00003809572	162067773	162068106

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 99.09.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 6.3357 / max 775.0952, expressed in 135 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59960	2.1026	112
59959	1.1804	104
59953	0.7889	101
59949	0.5050	96
59952	0.4074	93
59955	0.3138	65
59950	0.2774	74
59958	0.1633	66
59954	0.1569	59
59957	0.1387	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.09	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.46	gold quality
superior frontal gyrus	UBERON:0002661	96.66	gold quality
primary visual cortex	UBERON:0002436	96.52	gold quality
postcentral gyrus	UBERON:0002581	96.38	gold quality
parietal lobe	UBERON:0001872	96.23	gold quality
frontal pole	UBERON:0002795	96.18	gold quality
occipital lobe	UBERON:0002021	95.58	gold quality
pons	UBERON:0000988	95.34	gold quality
prefrontal cortex	UBERON:0000451	95.06	gold quality
endothelial cell	CL:0000115	94.93	gold quality
entorhinal cortex	UBERON:0002728	94.86	gold quality
superior vestibular nucleus	UBERON:0007227	94.74	gold quality
frontal cortex	UBERON:0001870	94.18	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.17	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.66	gold quality
cerebellar vermis	UBERON:0004720	93.56	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.50	gold quality
neocortex	UBERON:0001950	93.11	gold quality
cerebellar cortex	UBERON:0002129	92.48	gold quality
cerebellum	UBERON:0002037	92.43	gold quality
cerebral cortex	UBERON:0000956	92.41	gold quality
cerebellar hemisphere	UBERON:0002245	92.38	gold quality
right frontal lobe	UBERON:0002810	92.00	gold quality
paraflocculus	UBERON:0005351	91.75	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.71	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.57	gold quality
cingulate cortex	UBERON:0003027	90.34	gold quality
anterior cingulate cortex	UBERON:0009835	90.31	gold quality
telencephalon	UBERON:0001893	89.87	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	238.27
E-HCAD-35	yes	59.20
E-HCAD-25	yes	8.88
E-ANND-3	yes	7.45
E-GEOD-84465	yes	6.56
E-GEOD-137537	yes	6.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EPAS1, FOXO1, HIF1A, IKZF1

miRNA regulators (miRDB)

145 targeting GABRG2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus (PMID:11748509)
• The GABRG2 gene seems to confer a rare, rather than frequent, major susceptibility effect to common idiopathic absence epilepsy syndromes. (PMID:12117362)
• modeling of molecular configuration (PMID:12225856)
• using full-length or truncated chimeric subunits it was demonstrated that homologous sequences from gamma2 are important for assembly of GABA(A) receptors composed of alpha(1), beta(3), and gamma(2) subunits (PMID:12367595)
• GABRG2 gene might be neither a susceptibility gene for CAE nor in linkage disequilibrium with disease-predisposing sites in the Chinese population (PMID:12384214)
• GABRG2 gene might be one of the susceptibility factors for febrile seizures (PMID:12672902)
• No difference in allele frequency observed for severe myoclonic epilepsy of infancy patients compared to control population. (PMID:12694927)
• In the polymorphic SNPs, significant differences between methamphetamine users and controls were identified in the female sample of the GABA(A)alpha1 subunit gene, and novel SNP in GABA(A)gamma2 subunit gene. No associations were found in the male sample. (PMID:14569258)
• Ser171 and Tyr172 in the GABAA receptor gamma2 subunit constitute a critical motif for access to the cell surface (PMID:14593118)
• Properties of recombinant GABRG2 receptor vary significantly from one expression system to another most likely due to differences in endogenous modulators. (PMID:14625018)
• serine 171 may play a critical role in the formation and stabilization of an exposed turn structure that is part of the subunit interaction site. (PMID:14736867)
• Association of the GABA(B)R1 with the GABA(A) receptor gamma2S subunit robustly promotes cell surface expression of GABA(B)R1 in the absence of GABA(B)R2, that is usually required for efficient trafficking of GABA(B)R1 to the cell surface. (PMID:14966130)
• Human gamma 2L subunit is capable of forming fully functional GABA receptors by itself in Xenopus oocytes. (PMID:14981251)
• Two etomidate sites allosterically enhance GABA(A) receptor subunit gating independently of agonist binding. (PMID:15016806)
• extracellular domain models show subunit arrangement of GABA-A receptors (PMID:15033447)
• Gaba A receptor gamma 1/3 immunolabeling in prefrontal cortex of bipolar disorder subjects was more intense than controls and schizophrenics. There was a significant increase in gamma 1 subunit in bipolar subjects, with no difference in schizophrenics. (PMID:15257153)
• the GABAA receptor mutation linked to human epilepsy (gamma2R43Q) impairs cell surface expression of alphabetagamma receptors (PMID:15342642)
• The GABAA receptor gamma2 subunit R43Q mutation impaired GABA(A) receptor function by compromising receptor trafficking and reducing surface expression. (PMID:15470132)
• Models of GABA(A) receptors composed of alpha1 beta3 gamma2 subunits were generated and were used for predicting putative engineered cross-link sites between the alpha1 and the gamma2 subunit. (PMID:16412095)
• a conserved lysine in the TM2-3 of alpha1, beta2, and gamma2 of the GABA-A receptor has an asymmetric function in different GABAA subunits (PMID:16627470)
• Our results suggest that common variants of strong effect in GABRG2 do not appear to play a role in the development of common, complex forms of epilepsy. (PMID:16806831)
• alpha4beta3gamma2L receptors have unique kinetic properties that limit the range of GABA applications to which they can respond maximally. (PMID:17124266)
• the gamma2 subunit of the GABA receptor gene might be one of the susceptibility factors for idiopathic generalized epilepsies (PMID:17162195)
• In south china, the K289M mutation and single-nucleotide polymorphism rs211014 of the GABRD2 gene not releate to children with febrile seizures. (PMID:17641256)
• study found mutations of GABRA1, GABRB3, and GABRG2 appear not to play a major role in the development of familial primary dystonia (PMID:17880575)
• This suggests that mutations in the GABRG2 gene is not a prevalent cause of familial cases of FS and epilepsy or GEFS+ in Scandinavia. (PMID:17927801)
• 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)
• Febrile Seizure is not related to the most common mutations of GABRG2 in two Tunisian families (PMID:18175077)
• built homology models of the ion pores of alpha1beta2 and alpha1beta2gamma2 GABA(A)-R using coordinates of the nicotinic acetylcholine receptor as a template to determine details about the zinc binding site (PMID:18197653)
• Using wild type/mutated receptor subunits to identify compounds with anesthetic effect. (PMID:18292428)
• Novel ligand-gated gamma aminobutyric acid receptor(GABRG)2 and sodium channel voltage-gated type I alpha subunit (SCN1A) gene mutations are found in two unrelated Chinese families with generalized epilepsy with febrile seizures plus (GEFS+). (PMID:18566737)
• Seizure susceptibility was significantly reduced in mice where the GABRG2 Q43 allele was suppressed during development. (PMID:18825662)
• results of the present study suggest that hippocampal neurons expressing GABAAgamma receptor subunits resist the progression of neurofibrillary degeneration in Alzheimer disease hippocampus (PMID:19019179)
• the mutation of the GABA(A)-receptor gamma 2 subunit gene (GABRG2) in a Chinese family with generalized epilepsy with febrile seizures plus (GEFS+ ) and the genotype-phenotype correlations and its inheritance (PMID:19065515)
• Our results support that SCN1A is the responsible gene for GEFS+ in one of the two studied Tunisian families and suggest a positive association of an intronic SNP in the GABRG2 gene in both families. (PMID:19236456)
• 2(L287A) mutation introduced a modest defect in GABA-induced gating that simultaneously increased propofol potentiation. (PMID:19553237)
• These findings suggest that in the autistic group this downregulation of both benzodiazepine sites and GABA(A) receptors in the ACC. (PMID:19650112)
• The results of the present study suggest that GABRG2 may be involved in SCZ susceptibility, but further studies are required. (PMID:19682861)
• Report interaction of androsterone and progesterone with inhibitory ligand-gated ion channels: a patch clamp study. (PMID:19705103)
• 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)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabrg2	ENSDARG00000053665
mus_musculus	Gabrg2	ENSMUSG00000020436
rattus_norvegicus	Gabrg2	ENSRNOG00000003241

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), 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), 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 gamma-2 — P18507 (reviewed: P18507)

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

All UniProt accessions (20): A0A1W2PP56, A0A1W2PPN5, A0A1W2PPS4, A0A1W2PQ81, A0A1W2PQA6, A0A1W2PQR9, A0A1W2PQX1, A0A1W2PR49, A0A1W2PRM8, A0A1W2PRN4, A0A1W2PRU1, A0A1W2PRY3, A0A1W2PSF4, A0A1X7SBS5, A0A1X7SBZ8, A0A286YFI6, A8MWU7, P18507, E5RGJ0, E5RIG3

UniProt curated annotations — full annotation on UniProt →

Function. Gamma 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). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. Gamma-2/GABRG2-containing GABAARs are found at both synaptic and extrasynaptic sites. 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-2 or -3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation. Extrasynaptic gamma-2-containing receptors contribute to the tonic GABAergic inhibition. GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response in a gamma-2 subunit-controlled manner.

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. Interacts with GABARAP. Interacts with KIF21B. Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3. 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. Cell projection. Dendrite. Cytoplasmic vesicle membrane.

Post-translational modifications. Palmitoylated by ZDHHC3/GODZ; required for the accumulation of GABA(A) receptors at the postsynaptic membrane of inhibitory GABAergic synapses.

Disease relevance. Developmental and epileptic encephalopathy 74 (DEE74) [MIM:618396] 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. DEE74 is an autosomal dominant form with onset in the first year of life. The gene represented in this entry is involved in disease pathogenesis. Epilepsy, childhood absence 2 (ECA2) [MIM:607681] 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. Some individuals manifest febrile seizures. Absence seizures may either remit or persist into adulthood. Disease susceptibility is associated with variants affecting the gene represented in this entry. Febrile seizures, familial, 8 (FEB8) [MIM:607681] Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. The disease is caused by variants affecting the gene represented in this entry. Generalized epilepsy with febrile seizures plus 3 (GEFSP3) [MIM:607681] A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Allosterically activated by benzodiazepines. Activated by pentobarbital. Potentiated by etomidate, propofol, pregnanolone. Inhibited by the antagonist bicuculline. Inhibited by zinc ions. Potentiated by histamine.

Domain organisation. The extracellular domain contributes to synaptic contact formation. 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.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRG2 sub-subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P18507-2	1	yes
P18507-1	2
P18507-3	3

RefSeq proteins (15): NP_000807, NP_001362268, NP_001362269, NP_001362270, NP_001362271, NP_001362272, NP_001362273, NP_001362274, NP_001362275, NP_001362276, NP_001362277, NP_001362278, NP_001362279, NP_944493, NP_944494* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005437	GABRG-1/4	Family
IPR005439	GABBAg2_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 (65 total): strand 16, sequence variant 13, helix 8, topological domain 5, sequence conflict 5, turn 5, transmembrane region 4, glycosylation site 3, splice variant 2, signal peptide 1, chain 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

75 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8BHG	X-RAY DIFFRACTION	2.39
9EQG	ELECTRON MICROSCOPY	2.4
9FAS	ELECTRON MICROSCOPY	2.5
6X3T	ELECTRON MICROSCOPY	2.55
8VRN	ELECTRON MICROSCOPY	2.57
9FAJ	ELECTRON MICROSCOPY	2.6
9FAK	ELECTRON MICROSCOPY	2.6
9FGG	ELECTRON MICROSCOPY	2.6
8SGO	ELECTRON MICROSCOPY	2.65
7QNE	ELECTRON MICROSCOPY	2.7
9FG7	ELECTRON MICROSCOPY	2.7
9FG9	ELECTRON MICROSCOPY	2.7
8SID	ELECTRON MICROSCOPY	2.71
9FAP	ELECTRON MICROSCOPY	2.8
9FFV	ELECTRON MICROSCOPY	2.8
8VQY	ELECTRON MICROSCOPY	2.82
6X40	ELECTRON MICROSCOPY	2.86
8DD2	ELECTRON MICROSCOPY	2.9
8DD3	ELECTRON MICROSCOPY	2.9
9CRS	ELECTRON MICROSCOPY	2.9
9FAN	ELECTRON MICROSCOPY	2.9
9FAQ	ELECTRON MICROSCOPY	2.9
9FAR	ELECTRON MICROSCOPY	2.9
9FAW	ELECTRON MICROSCOPY	2.9
9FAX	ELECTRON MICROSCOPY	2.9
9FG8	ELECTRON MICROSCOPY	2.9
9FGF	ELECTRON MICROSCOPY	2.9
6X3X	ELECTRON MICROSCOPY	2.92
9DRX	ELECTRON MICROSCOPY	2.95
8SI9	ELECTRON MICROSCOPY	2.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18507-F1	77.41	0.59

Antibody-complex structures (SAbDab): 60 — 6D6T, 6D6U, 6HUG, 6HUJ, 6HUK, 6HUO, 6HUP, 6I53, 6X3S, 6X3T, 6X3U, 6X3V, 6X3W, 6X3X, 6X3Z, 6X40, 7QNA, 7QNB, 7QNE, 7T0W, 7T0Z, 8DD2, 8DD3, 8SGO, 8SI9 (+35 more)

Functional residue map

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

Disulfide bonds (1): 190–204

Glycosylation sites (3): 52, 129, 247

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: 465 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_274, GOBP_BEHAVIOR, GOBP_SYNAPSE_ASSEMBLY, LFA1_Q6, GOBP_ADULT_BEHAVIOR, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, TTGGGAG_MIR150, GOBP_CELL_CELL_SIGNALING, MODULE_66, PAX8_B, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (12): gamma-aminobutyric acid signaling pathway (GO:0007214), post-embryonic development (GO:0009791), adult behavior (GO:0030534), synaptic transmission, GABAergic (GO:0051932), cellular response to histamine (GO:0071420), chloride transmembrane transport (GO:1902476), inhibitory synapse assembly (GO:1904862), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), chemical synaptic transmission (GO:0007268), monoatomic ion transmembrane transport (GO:0034220), regulation of postsynaptic membrane potential (GO:0060078)

GO Molecular Function (9): GABA-A receptor activity (GO:0004890), chloride channel activity (GO:0005254), benzodiazepine receptor activity (GO:0008503), GABA-gated chloride ion channel activity (GO:0022851), 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), protein binding (GO:0005515)

GO Cellular Component (17): plasma membrane (GO:0005886), axon (GO:0030424), cytoplasmic vesicle membrane (GO:0030659), dendrite membrane (GO:0032590), chloride channel complex (GO:0034707), dendritic spine (GO:0043197), postsynaptic membrane (GO:0045211), 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 (GO:0031410), cell projection (GO:0042995), synapse (GO:0045202), synaptic membrane (GO:0097060)

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
synapse	3
cellular anatomical structure	3
GABA receptor activity	2
transmitter-gated monoatomic ion channel activity	2
neuron projection	2
dendrite	2
postsynapse	2
synaptic membrane	2
cell-cell signaling	1
multicellular organism development	1
multicellular organismal process	1
behavior	1
chemical synaptic transmission	1
response to histamine	1
cellular response to nitrogen compound	1
chloride transport	1
monoatomic anion transmembrane transport	1
synapse assembly	1
transport	1
monoatomic anion transport	1
inorganic anion transport	1
anterograde trans-synaptic signaling	1
monoatomic ion transport	1
transmembrane transport	1
regulation of membrane potential	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
neurotransmitter receptor activity	1
chloride channel activity	1
ligand-gated monoatomic anion channel activity	1
regulation of postsynaptic membrane potential	1
signaling receptor activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
ligand-gated monoatomic ion channel activity	1
binding	1
membrane	1
cell periphery	1
vesicle membrane	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

2346 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRG2	SCN1A	P35498	945
GABRG2	SCN1B	Q07699	943
GABRG2	CLCN2	P51788	892
GABRG2	SCN9A	Q15858	861
GABRG2	GPHN	Q9NQX3	739
GABRG2	CACNA1H	O95180	736
GABRG2	GABBR1	Q9UBS5	700
GABRG2	SCN2A	Q99250	697
GABRG2	GABARAP	O95166	687
GABRG2	SCN8A	Q9UQD0	682
GABRG2	PCDH19	Q8TAB3	676
GABRG2	SLC6A1	P30531	634
GABRG2	GAD1	Q99259	626
GABRG2	KCNQ2	O43526	614
GABRG2	PCDH10	Q9P2E7	603

IntAct

12 interactions, top by confidence:

A	B	Type	Score
GABRA1	GABRG2	psi-mi:“MI:0915”(physical association)	0.550
GABRG2	GPAA1	psi-mi:“MI:0914”(association)	0.530
GABRG2	NOVA1	psi-mi:“MI:0915”(physical association)	0.400
	GABRA1	psi-mi:“MI:0915”(physical association)	0.400
	GABRG2	psi-mi:“MI:0915”(physical association)	0.400
CFTR	GABRG2	psi-mi:“MI:0915”(physical association)	0.370
GABRG2	B4GALT5	psi-mi:“MI:0914”(association)	0.350
GABRA4	GABRG2	psi-mi:“MI:0915”(physical association)	0.320
GABRB3	GABRG2	psi-mi:“MI:0915”(physical association)	0.320

BioGRID (34): GABRG1 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), DNAJC18 (Affinity Capture-MS), BSCL2 (Affinity Capture-MS), B4GALT5 (Affinity Capture-MS), CANX (Affinity Capture-MS), GPAA1 (Affinity Capture-MS), LCLAT1 (Affinity Capture-MS), ABHD14A (Affinity Capture-MS), CPT1A (Affinity Capture-MS), GABRG2 (FRET), BSCL2 (Affinity Capture-MS), GABRG2 (Protein-peptide), USP33 (Affinity Capture-MS), GABRG1 (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: 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

7 interactions.

A	Effect	B	Mechanism
GABRG2	“form complex”	“GABA-A (a1-b1-g2) receptor”	binding
GABRG2	“form complex”	“GABA-A (a2-b1-g2) receptor”	binding
GABRG2	“form complex”	“GABA-A (a3-b1-g2) receptor”	binding
GABRG2	“form complex”	“GABA-A (a4-b1-g2) receptor”	binding
GABRG2	“form complex”	“GABA-A (a6-b1-g2) receptor”	binding
GABRG2	“form complex”	“GABA-A (a5-b1-g2) receptor”	binding
PRKCE	“down-regulates activity”	GABRG2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	84
Likely pathogenic	52
Uncertain significance	341
Likely benign	198
Benign	35

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1066278	NM_198904.4(GABRG2):c.769+1G>A	Pathogenic
1069676	NC_000005.9:g.(?161495006)(161580374_?)del	Pathogenic
1071103	NM_198904.4(GABRG2):c.429dup (p.Lys144fs)	Pathogenic
1073528	NM_198904.4(GABRG2):c.1277del (p.Phe426fs)	Pathogenic
1075793	NM_198904.4(GABRG2):c.1224_1225insCA (p.Asp409fs)	Pathogenic
127233	NM_198904.4(GABRG2):c.247C>T (p.Pro83Ser)	Pathogenic
1352245	NM_198904.4(GABRG2):c.917C>T (p.Ser306Phe)	Pathogenic
1385670	NC_000005.9:g.(?161569150)(161580374_?)del	Pathogenic
1457057	NM_198904.4(GABRG2):c.498del (p.Asn167fs)	Pathogenic
1457679	NC_000005.9:g.(?161520814)(161580374_?)del	Pathogenic
1459641	NC_000005.9:g.(?161495006)(161495132_?)del	Pathogenic
1459966	NC_000005.9:g.(?161495006)(161569342_?)del	Pathogenic
1460159	NC_000005.9:g.(?161495006)(161528343_?)del	Pathogenic
1460405	NC_000005.9:g.(?161495006)(161531052_?)del	Pathogenic
1508087	NM_198904.4(GABRG2):c.929C>T (p.Thr310Ile)	Pathogenic
1516815	NM_198904.4(GABRG2):c.940A>T (p.Thr314Ser)	Pathogenic
153230	GRCh38/hg38 5q34(chr5:161954028-162107018)x1	Pathogenic
16207	NM_198904.4(GABRG2):c.983A>T (p.Lys328Met)	Pathogenic
16208	NM_198904.4(GABRG2):c.245G>A (p.Arg82Gln)	Pathogenic
16209	NM_198904.4(GABRG2):c.1192C>T (p.Gln398Ter)	Pathogenic
16210	NM_198904.4(GABRG2):c.769+2T>G	Pathogenic
16211	NM_198904.4(GABRG2):c.529C>G (p.Arg177Gly)	Pathogenic
1685837	NM_198904.4(GABRG2):c.929C>G (p.Thr310Ser)	Pathogenic
1993170	NM_198904.4(GABRG2):c.386del (p.Asn129fs)	Pathogenic
2012801	NM_198904.4(GABRG2):c.570C>A (p.Cys190Ter)	Pathogenic
2018794	NM_198904.4(GABRG2):c.852_858del (p.Leu285fs)	Pathogenic
2027142	NM_198904.4(GABRG2):c.363G>A (p.Trp121Ter)	Pathogenic
205540	NM_198904.4(GABRG2):c.406C>T (p.Arg136Ter)	Pathogenic
205545	NM_198904.4(GABRG2):c.770-1G>A	Pathogenic
205546	NM_198904.4(GABRG2):c.844C>A (p.Pro282Thr)	Pathogenic

SpliceAI

1393 predictions. Top by Δscore:

Variant	Effect	Δscore
5:162093823:CTTA:C	acceptor_loss	1.0000
5:162093826:A:AG	acceptor_gain	1.0000
5:162093827:G:GG	acceptor_gain	1.0000
5:162093827:GCT:G	acceptor_gain	1.0000
5:162093827:GCTTC:G	acceptor_gain	1.0000
5:162093943:G:GT	donor_gain	1.0000
5:162093976:GGAG:G	donor_gain	1.0000
5:162093976:GGAGG:G	donor_loss	1.0000
5:162093977:G:GT	donor_gain	1.0000
5:162093977:GAGG:G	donor_loss	1.0000
5:162093978:AGGTT:A	donor_loss	1.0000
5:162093979:GGTT:G	donor_loss	1.0000
5:162093980:G:GA	donor_loss	1.0000
5:162095492:C:G	acceptor_gain	1.0000
5:162095492:CA:C	acceptor_loss	1.0000
5:162095493:A:AG	acceptor_gain	1.0000
5:162095493:AGT:A	acceptor_gain	1.0000
5:162095494:G:A	acceptor_loss	1.0000
5:162095494:G:GA	acceptor_gain	1.0000
5:162095494:GT:G	acceptor_gain	1.0000
5:162095494:GTG:G	acceptor_gain	1.0000
5:162095494:GTGA:G	acceptor_gain	1.0000
5:162095494:GTGAA:G	acceptor_gain	1.0000
5:162095559:TATGG:T	donor_loss	1.0000
5:162095561:TGGT:T	donor_loss	1.0000
5:162095562:GGTGA:G	donor_loss	1.0000
5:162095563:G:GA	donor_loss	1.0000
5:162095563:G:GG	donor_gain	1.0000
5:162095564:TGA:T	donor_loss	1.0000
5:162095565:GAG:G	donor_loss	1.0000

AlphaMissense

3087 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:162093938:T:C	L73P	1.000
5:162093962:T:C	L81P	1.000
5:162093967:C:T	P83S	1.000
5:162093968:C:A	P83H	1.000
5:162095539:G:C	G102R	1.000
5:162095562:G:A	M109I	1.000
5:162095562:G:C	M109I	1.000
5:162095562:G:T	M109I	1.000
5:162097666:A:C	Q119P	1.000
5:162097671:T:A	W121R	1.000
5:162097671:T:C	W121R	1.000
5:162097673:G:C	W121C	1.000
5:162097673:G:T	W121C	1.000
5:162097677:G:T	D123Y	1.000
5:162097678:A:T	D123V	1.000
5:162097684:G:C	R125P	1.000
5:162097687:T:C	L126S	1.000
5:162097692:T:C	F128L	1.000
5:162097694:T:A	F128L	1.000
5:162097694:T:G	F128L	1.000
5:162097746:T:A	W146R	1.000
5:162097746:T:C	W146R	1.000
5:162097747:G:C	W146S	1.000
5:162097748:G:C	W146C	1.000
5:162097748:G:T	W146C	1.000
5:162097752:C:T	P148S	1.000
5:162097753:C:A	P148Q	1.000
5:162097753:C:G	P148R	1.000
5:162097755:G:C	D149H	1.000
5:162097811:C:A	N167K	1.000

dbSNP variants (sampled 300 via entrez): RS1000003327 (5:162102918 A>T), RS1000013998 (5:162145946 A>G), RS1000047317 (5:162142682 A>G), RS1000103452 (5:162154368 T>C), RS1000149634 (5:162070486 T>A), RS1000152505 (5:162146299 A>C), RS1000152696 (5:162111051 C>A), RS1000155960 (5:162154041 A>C), RS1000177549 (5:162139360 G>GT), RS1000196892 (5:162092640 C>T), RS1000210968 (5:162096089 C>G), RS1000238043 (5:162135474 T>C), RS1000255870 (5:162092845 T>C,G), RS1000266086 (5:162090556 T>C), RS1000282926 (5:162116256 T>C)

Disease associations

OMIM: gene MIM:137164 | disease phenotypes: MIM:607681, MIM:611277, MIM:618396, MIM:118220, MIM:600513, MIM:308350, MIM:606369, MIM:117100, MIM:600669, MIM:611136

GenCC curated gene-disease

Disease	Classification	Inheritance
epilepsy	Definitive	Autosomal dominant
febrile seizures, familial, 8	Strong	Autosomal dominant
developmental and epileptic encephalopathy, 74	Strong	Autosomal dominant
self-limited epilepsy with centrotemporal spikes	Supportive	Autosomal dominant
Dravet syndrome	Supportive	Autosomal dominant
generalized epilepsy with febrile seizures plus	Supportive	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
epilepsy	Definitive	AD

Mondo (17): febrile seizures, familial, 8 (MONDO:0011891), developmental and epileptic encephalopathy, 74 (MONDO:0032725), Charcot-Marie-Tooth disease (MONDO:0015626), sudden unexplained death in childhood (MONDO:1010117), familial sleep-related hypermotor epilepsy (MONDO:0000030), genetic developmental and epileptic encephalopathy (MONDO:0100062), epilepsy (MONDO:0005027), Lennox-Gastaut syndrome (MONDO:0016532), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), intellectual disability (MONDO:0001071), idiopathic generalized epilepsy (MONDO:0005579), epilepsy, idiopathic generalized, susceptibility to, 13 (MONDO:0012627), esophageal atresia (MONDO:0001044), pyloric stenosis (MONDO:0001561), (MONDO:0011794)

Orphanet (8): Genetic epilepsy with febrile seizure plus (Orphanet:36387), Childhood absence epilepsy (Orphanet:64280), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Sleep-related hypermotor epilepsy (Orphanet:98784), Lennox-Gastaut syndrome (Orphanet:2382), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Juvenile myoclonic epilepsy (Orphanet:307), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

143 total (30 of 143 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000466	Limited neck range of motion
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:0000712	Emotional lability
HP:0000716	Depression
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000980	Pallor
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:0001266	Choreoathetosis
HP:0001268	Mental deterioration

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST003075_70	Cognitive decline rate in late mild cognitive impairment	6.000000e-07
GCST003123_15	Severe influenza A (H1N1) infection	2.000000e-13
GCST003265_56	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST004029_39	Angiotensin-converting enzyme inhibitor intolerance	8.000000e-09
GCST010105_171	Nicotine dependence symptom count	5.000000e-06
GCST010105_92	Nicotine dependence symptom count	5.000000e-06
GCST011140_3	Glucagon levels in response to oral glucose tolerance test (decremental area under the curve for 0-30 minutes)	3.000000e-06
GCST012490_440	Femur bone mineral density x serum urate levels interaction	3.000000e-08
GCST012490_54	Femur bone mineral density x serum urate levels interaction	2.000000e-11
GCST90000014_2	Parkinson’s disease motor subtype (tremor dominant vs postural instability/gait difficulty)	2.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:1001488	influenza A (H1N1)
EFO:0004713	FEV/FVC ratio
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0009262	nicotine dependence symptom count
EFO:0008463	glucagon measurement
EFO:0004531	urate measurement

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D004827	Epilepsy	C10.228.140.490
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D017219	Gastric Outlet Obstruction	C06.405.748.340
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
D011707	Pyloric Stenosis	C06.405.748.340.690
C579932	Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (supp.)
C567002	Epilepsy, Childhood Absence, Susceptibility To, 4 (supp.)
C562694	Epilepsy, Idiopathic Generalized (supp.)
C565811	Generalized Epilepsy With Febrile Seizures Plus, Type 3 (supp.)
C565808	Generalized Epilepsy with Febrile Seizures Plus (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (18): CHEMBL2093872 (PROTEIN COMPLEX GROUP), CHEMBL2094120 (PROTEIN COMPLEX), CHEMBL2094121 (PROTEIN COMPLEX), CHEMBL2094122 (PROTEIN COMPLEX), CHEMBL2094130 (PROTEIN COMPLEX), CHEMBL2095172 (PROTEIN COMPLEX), CHEMBL2095190 (PROTEIN COMPLEX), CHEMBL2109243 (PROTEIN COMPLEX GROUP), CHEMBL2111339 (PROTEIN COMPLEX), CHEMBL2111366 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

55 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 532,203 (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
CHEMBL451	CHLORDIAZEPOXIDE	4	36,533
CHEMBL646	TRIAZOLAM	4	21,589
CHEMBL911	ZOLPIDEM	4	17,821
CHEMBL15891	LINDANE	4	83,653
CHEMBL526	PROPOFOL	4	28,835
CHEMBL1521	ZALEPLON	4	9,958
CHEMBL1983350	STIRIPENTOL	4	2,890
CHEMBL4105630	ZURANOLONE	4	290
CHEMBL661	ALPRAZOLAM	4	130,677
CHEMBL681	ETOMIDATE	4	8,462
CHEMBL1522	ESZOPICLONE	4	6,548
CHEMBL448	PENTOBARBITAL	4
CHEMBL1014	CANDESARTAN CILEXETIL	4
CHEMBL1064	SIMVASTATIN	4
CHEMBL1106	EPINASTINE	4
CHEMBL146095	GLAFENINE	4
CHEMBL222559	TIPRANAVIR	4
CHEMBL297302	BENPERIDOL	4
CHEMBL3187365	ASENAPINE	4
CHEMBL408	TROGLITAZONE	4
CHEMBL42	CLOZAPINE	4

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs211037	GABRG2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

Binding affinities (BindingDB)

370 measured of 382 human assays (385 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

4309 potent at pChembl≥5 of 4573 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	PHENAZEPAM
10.30	Ki	0.05	nM	CGS-8216
10.30	Ki	0.05	nM	CHEMBL4243764
10.22	Ki	0.06	nM	PHENAZEPAM
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	CHEMBL487686
9.92	Ki	0.12	nM	CHEMBL488283
9.92	Ki	0.12	nM	CHEMBL469477
9.92	Ki	0.12	nM	PHENAZEPAM
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	CHEMBL487687
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	CHEMBL3274851
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	CHEMBL50763
9.77	Ki	0.17	nM	CHEMBL3144849
9.77	Ki	0.17	nM	CHEMBL3144615
9.77	Ki	0.17	nM	CHEMBL299210

PubChem BioAssay actives

2932 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
1,4,5,6-tetrahydropyrimidine-5-carboxylic acid	1184360: Agonist activity at human GABAAalpha1beta2gamma2S receptor expressed in tsA-201cells by FLIPR membrane potential blue assay	ec50	<0.0001	uM
6-amino-2-methylpyridine-3-carboxylic acid	1184360: Agonist activity at human GABAAalpha1beta2gamma2S receptor expressed in tsA-201cells by FLIPR membrane potential blue assay	ec50	<0.0001	uM
piperidine-4-carboxylic acid	1184360: Agonist activity at human GABAAalpha1beta2gamma2S receptor expressed in tsA-201cells by FLIPR membrane potential blue assay	ec50	<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
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
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
7-bromo-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one	1889906: Displacement of [3H]flunitrazepam from human recombinant alpha1beta2gamma2 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	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	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
[7-chloro-3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-4H-imidazo[1,5-a]quinoxalin-5-yl]-morpholin-4-ylmethanone	72905: Displacement of [3H]flunitrazepam from GABA-A receptor alpha-1-beta-2-gamma-2 subunits expressed in Sf9 cells	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
[3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-6-fluoro-4H-imidazo[1,5-a]quinoxalin-5-yl]-morpholin-4-ylmethanone	72906: Displacement of [3H]Flunitrazepam from GABA-A receptor alpha-1-beta-2-gamma-2 subunits expressed in Sf9 cells	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
Flumazenil	1798656: Radioligand Binding Assay from Article 10.1021/jm800889m: “Structural Requirements for Eszopiclone and Zolpidem Binding to the gamma-Aminobutyric Acid Type-A (GABAA) Receptor Are Different.”	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

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

Chemical	Actions (top 5)	PubMed papers
gamma-Aminobutyric Acid	increases reaction, affects binding, decreases reaction, increases activity, affects cotreatment (+1 more)	17
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Propofol	increases reaction, affects reaction, affects cotreatment, affects binding, decreases reaction (+1 more)	4
1-(3-chlorophenyl)piperazine	increases reaction, affects cotreatment, affects reaction, increases activity, affects binding (+2 more)	3
Hexachlorocyclohexane	affects binding, decreases reaction, increases activity, increases reaction	3
Diazepam	affects binding, increases activity, increases reaction, affects response to substance	3
2,4,2’,4’-tetrachlorobiphenyl	decreases reaction, affects binding, increases activity, affects cotreatment, increases reaction	2
tert-butylbicyclophosphorothionate	affects binding, decreases reaction	2
delta-hexachlorocyclohexane	decreases activity, affects binding, affects cotreatment, increases activity, increases reaction (+1 more)	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Flunitrazepam	increases reaction, increases activity, affects reaction, affects binding	2
Methamphetamine	decreases reaction, increases activity, increases response to substance, affects cotreatment	2
Pentobarbital	affects binding, decreases reaction, increases activity, increases reaction, affects cotreatment	2
Picrotoxin	decreases reaction, increases activity, affects binding	2
3,4-Methylenedioxyamphetamine	affects cotreatment, affects reaction, increases activity, affects binding, decreases activity (+1 more)	2
6-methoxyflavone	affects binding, increases activity, increases reaction	1
6-methoxyflavanone	increases activity, increases reaction, affects binding	1
beta-thujone	affects binding, decreases reaction, increases activity	1
1-benzylpiperazine	decreases reaction, increases activity, affects binding	1
bisphenol A	affects cotreatment, increases methylation	1
carvone	affects binding, increases activity, increases reaction	1
2,5,2’,5’-tetrachlorobiphenyl	affects binding, affects cotreatment, increases activity	1
tetramethylenedisulfotetramine	affects binding, decreases reaction, increases activity, increases reaction	1
trichostatin A	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects binding, decreases reaction, increases activity	1
arsenite	increases methylation	1
bromoform	affects activity, affects binding	1
sodium arsenite	increases expression	1
1-(3-trifluoromethylphenyl)piperazine	increases activity, affects binding, decreases reaction	1
menthone	affects binding, increases activity, increases reaction	1

ChEMBL screening assays

1155 unique, capped per target: 940 binding, 201 functional, 10 admet, 4 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

14 cell lines: 7 transformed cell line, 3 cancer cell line, 3 spontaneously immortalized cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AY57	GM25431	Finite cell line	Female
CVCL_B8GM	Abcam HCT 116 GABRG2 KO	Cancer cell line	Male
CVCL_B8W7	Abcam MCF-7 GABRG2 KO	Cancer cell line	Female
CVCL_B9IV	Abcam A-549 GABRG2 KO	Cancer cell line	Male
CVCL_C0XQ	B’SYS CHO alpha1beta2gamma2 GABA(A)	Spontaneously immortalized cell line	Female
CVCL_C0YP	CHO-K1 GABA(A)R alpha1beta2gamma2L	Spontaneously immortalized cell line	Female
CVCL_C5TV	GABAA1-CHO	Spontaneously immortalized cell line	Female
CVCL_C9E7	B’SYS LTK alpha1beta2gamma2 GABA(A)	Transformed cell line	Male
CVCL_D1JK	PrecisION hGABAA alpha1/beta3/gamma2-HEK	Transformed cell line	Female
CVCL_D1JL	PrecisION hGABAA alpha3/beta3/gamma2-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy