GABRA5

Summary

GABRA5 (gamma-aminobutyric acid type A receptor subunit alpha5, HGNC:4079) is a protein-coding gene on chromosome 15q12, encoding Gamma-aminobutyric acid receptor subunit alpha-5 (P31644). Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. Transcript variants utilizing three different alternative non-coding first exons have been described.

Source: NCBI Gene 2558 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 79 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 140 total — 8 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 60
• Druggable target: yes — 27 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000810

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4079
Approved symbol	GABRA5
Name	gamma-aminobutyric acid type A receptor subunit alpha5
Location	15q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000186297
Ensembl biotype	protein_coding
OMIM	137142
Entrez	2558

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000335625, ENST00000355395, ENST00000400081, ENST00000554038, ENST00000554083, ENST00000554596, ENST00000554599, ENST00000555060, ENST00000555182, ENST00000557449, ENST00000557484, ENST00000879566, ENST00000951856

RefSeq mRNA: 2 — MANE Select: NM_000810 NM_000810, NM_001165037

CCDS: CCDS45194

Canonical transcript exons

ENST00000335625 — 11 exons

Exon	Start	End
ENSE00001333513	26937185	26937328
ENSE00001372316	26914803	26914885
ENSE00001387903	26868729	26868793
ENSE00001430185	26883166	26883233
ENSE00001783227	26939925	26940077
ENSE00002440125	26867062	26867111
ENSE00002493541	26943215	26943426
ENSE00003566900	26869175	26869334
ENSE00003631305	26880846	26880967
ENSE00003784216	26883337	26883557
ENSE00003846485	26947934	26949208

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 95.91.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6591 / max 243.8537, expressed in 308 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
145575	0.8893	199
145578	0.4155	89
145584	0.2520	61
145580	0.2466	58
145573	0.1970	88
145579	0.1147	48
145576	0.1115	60
207444	0.0943	42
145583	0.0669	38
145574	0.0665	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	95.91	gold quality
prefrontal cortex	UBERON:0000451	93.91	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.09	gold quality
cingulate cortex	UBERON:0003027	92.99	gold quality
anterior cingulate cortex	UBERON:0009835	92.95	gold quality
orbitofrontal cortex	UBERON:0004167	92.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.95	gold quality
Ammon’s horn	UBERON:0001954	91.40	gold quality
frontal cortex	UBERON:0001870	91.17	gold quality
CA1 field of hippocampus	UBERON:0003881	90.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.69	gold quality
frontal pole	UBERON:0002795	90.56	gold quality
caudate nucleus	UBERON:0001873	90.54	gold quality
neocortex	UBERON:0001950	90.42	gold quality
cerebral cortex	UBERON:0000956	90.20	gold quality
cortical plate	UBERON:0005343	89.78	gold quality
telencephalon	UBERON:0001893	89.46	gold quality
right frontal lobe	UBERON:0002810	89.37	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.75	gold quality
amygdala	UBERON:0001876	88.29	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.58	gold quality
putamen	UBERON:0001874	87.40	gold quality
temporal lobe	UBERON:0001871	87.39	gold quality
entorhinal cortex	UBERON:0002728	86.65	gold quality
superior frontal gyrus	UBERON:0002661	86.17	gold quality
forebrain	UBERON:0001890	85.10	gold quality
postcentral gyrus	UBERON:0002581	82.11	gold quality
parietal lobe	UBERON:0001872	81.56	gold quality
hypothalamus	UBERON:0001898	80.61	gold quality
middle frontal gyrus	UBERON:0002702	80.32	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

131 targeting GABRA5, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
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-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-141-3P	99.94	72.79	2421

Literature-anchored findings (GeneRIF, showing 26)

• extracellular domain models show subunit arrangement of GABA-A receptors (PMID:15033447)
• These results suggest that the GABRA5 gene may confer susceptibility to bipolar I disorder. (PMID:15882799)
• GABA(A) receptor alpha5 subunit as a candidate gene for autism and bipolar disorder; observations suggest parent-of-origin and gain-of-function effects (PMID:17353214)
• The ratios of beta(3)/beta(2) and alpha(5)/alpha(1) subunit protein expression in Angelman syndrome cortex were significantly decreased when compared with controls. (PMID:20692323)
• In subjects with schizophrenia, mean GABA (A) alpha5 rerceptor subunit mRNA expression is 15% lower in layer 4 of the dorsolateral prefrontal cortex. (PMID:20843900)
• Data indicate the selectivity of some selected compounds were assessed in recombinant alpha(1)beta(2)gamma(2)L, alpha(2)beta(1)gamma(2)L, and alpha(5)beta(2)gamma(2)L GABA(A) receptors. (PMID:21751815)
• These results provide initial evidence of a GABAA alpha5 deficit in autism spectrum disorder and support further investigations of the GABA system in this disorder. (PMID:22546616)
• The alpha5 nicotinic receptor GABAergic neurons form a link from the medial habenula to the serotonergic brain centers. (PMID:24227714)
• Findings provide genetic evidence for the involvement of the genes GABRB3 and GABRA5 in the susceptibility to panic disorder (PMID:24755890)
• 1,2-dichlorohexafluorocyclobutane enhancement of GABRA5 activity is abolished by GABRB3 mutations. (PMID:25211390)
• This study showed that in male groups, the expression of GABRA5 was generally lower in schizophrenia cases compared to the control. (PMID:25660468)
• Study found that a significant portion of GABAergic postsynaptic compartments contain the alpha5 GABAAR subunit, both in vitro and in vivo (PMID:25663431)
• Report benzodiazepine derivative as GABA-site inhibitor of extra-synaptic GABAA alpha5 receptors. (PMID:26169564)
• Study found a significant reduction in [(11)C]Ro15 4513 binding in the nucleus accumbens in an opiate-dependent compared with the healthy control group. Study suggests that reduced GABA A receptor alpha5 levels in the nucleus accumbens are associated with addiction. (PMID:26876472)
• GABAA receptor gene polymorphisms can predict symptom-based and developmental deficits in autistic spectrum disorders individuals. (PMID:28607477)
• Meta-analysis showed that GABRA5 polymorphisms are not significantly associated with autism. (PMID:29725984)
• Low GABRA5 expression typified hyperproliferative tumors, and loss of taurine signaling correlated with reduced patient survival, suggesting this tumor suppressive mechanism operates in vivo. (PMID:29787571)
• The GABRA5 p.V294L variant produced receptors that were 10-times more sensitive to GABA but had reduced maximal GABA-evoked current due to increased receptor desensitization. (PMID:29961870)
• cryo-EM structure of the human alpha5beta3 GABAA receptor (PMID:30140029)
• both total GABAA and GABAA alpha5 receptor availability in two positron emission tomography imaging studies, are reported. (PMID:30282698)
• study identified GABRA5 as a causative gene for early onset epileptic encephalopathy and expands the mutant GABRA1 phenotypic spectrum, supporting growing evidence that defects in GABAergic neurotransmission contribute to early onset epileptic encephalopathy phenotypes. (PMID:31056671)
• Sex Differences in the Expression of the alpha5 Subunit of the GABAA Receptor in Alcoholics with and without Cirrhosis of the Liver. (PMID:31840824)
• An association study in the Taiwan Biobank elicits the GABAA receptor genes GABRB3, GABRA5, and GABRG3 as candidate loci for sleep duration in the Taiwanese population. (PMID:34530807)
• GABA Receptor SNPs and Elevated Plasma GABA Levels Affect the Severity of the Indian ASD Probands. (PMID:35562522)
• Effects of alpha5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer’s disease. (PMID:35822698)
• Novel variants in GABAA receptor subunits: A possible association with benzodiazepine resistance in patients with drug-resistant epilepsy. (PMID:36469977)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabra5	ENSDARG00000070730
mus_musculus	Gabra5	ENSMUSG00000055078
rattus_norvegicus	Gabra5	ENSRNOG00000010803

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), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038)

Protein

Protein identifiers

Gamma-aminobutyric acid receptor subunit alpha-5 — P31644 (reviewed: P31644)

Alternative names: GABA(A) receptor subunit alpha-5

All UniProt accessions (7): P31644, G3V296, G3V2G8, G3V2K2, G3V2Q9, G3V2Y5, G3V408

UniProt curated annotations — full annotation on UniProt →

Function. Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain. GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. GABAARs containing alpha-5/GABRA5 subunits are mainly extrasynaptic and contribute to the tonic GABAergic inhibition in the hippocampus. Extrasynaptic alpha-5-containing GABAARs in CA1 pyramidal neurons play a role in learning and memory processes.

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.

Subcellular location. Postsynaptic cell membrane. Cell membrane.

Disease relevance. Developmental and epileptic encephalopathy 79 (DEE79) [MIM:618559] 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. DEE79 is an autosomal dominant form characterized by onset of refractory seizures in the first months of life. Brain imaging may show hypomyelination, cerebral atrophy and thinning of the corpus callosum. The disease is caused by variants affecting the gene represented in this entry.

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.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA5 sub-subfamily.

RefSeq proteins (2): NP_000801, NP_001158509 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001390	GABAAa_rcpt	Family
IPR005435	GABBAa5_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
IPR047024	Gabra-1-6_TM	Domain

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (54 total): strand 15, helix 9, turn 7, topological domain 5, glycosylation site 4, transmembrane region 4, sequence variant 3, binding site 2, signal peptide 1, chain 1, region of interest 1, disulfide bond 1, cross-link 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
8BHG	X-RAY DIFFRACTION	2.39
8BHB	ELECTRON MICROSCOPY	2.54
8BGI	X-RAY DIFFRACTION	2.56
8BHA	ELECTRON MICROSCOPY	2.67
8BHI	ELECTRON MICROSCOPY	2.67
8BHO	ELECTRON MICROSCOPY	2.93
8BHM	ELECTRON MICROSCOPY	2.95
9HNS	ELECTRON MICROSCOPY	3.1
9RL5	ELECTRON MICROSCOPY	3.1
9RPB	ELECTRON MICROSCOPY	3.1
9HAA	ELECTRON MICROSCOPY	3.14
9HNR	ELECTRON MICROSCOPY	3.17
5O8F	X-RAY DIFFRACTION	3.2
8BEJ	ELECTRON MICROSCOPY	3.24
8BHS	ELECTRON MICROSCOPY	3.24
5OJM	X-RAY DIFFRACTION	3.3
8BHK	ELECTRON MICROSCOPY	3.3
8BHQ	ELECTRON MICROSCOPY	3.3
9HNT	ELECTRON MICROSCOPY	3.32
9HUM	ELECTRON MICROSCOPY	3.35
8BHR	ELECTRON MICROSCOPY	3.38
6A96	ELECTRON MICROSCOPY	3.51
9HNQ	ELECTRON MICROSCOPY	3.81

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31644-F1	81.67	0.61

Antibody-complex structures (SAbDab): 3 — 5O8F, 5OJM, 6A96

Functional residue map

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

Ligand- & substrate-binding residues (2): 101; 164

Post-translational modifications (1): 355

Disulfide bonds (1): 173–187

Glycosylation sites (4): 45, 145, 207, 236

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-977443	GABA receptor activation

MSigDB gene sets: 274 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_EPITHELIUM_DEVELOPMENT, TAATAAT_MIR126, GOBP_COGNITION, MODULE_274, GOBP_BEHAVIOR, GOBP_SYNAPSE_ASSEMBLY, GOBP_ASSOCIATIVE_LEARNING, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, GOBP_NEUROGENESIS, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, GOBP_CELL_CELL_SIGNALING, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (17): behavioral fear response (GO:0001662), signal transduction (GO:0007165), gamma-aminobutyric acid signaling pathway (GO:0007214), associative learning (GO:0008306), synaptic transmission, GABAergic (GO:0051932), inner ear receptor cell development (GO:0060119), innervation (GO:0060384), 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), monoatomic ion transmembrane transport (GO:0034220), neuron development (GO:0048666), regulation of postsynaptic membrane potential (GO:0060078), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (11): GABA-A receptor activity (GO:0004890), GABA-gated chloride ion channel activity (GO:0022851), signaling receptor activity (GO:0038023), GABA receptor binding (GO:0050811), ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential (GO:0099507), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), chloride channel activity (GO:0005254), benzodiazepine receptor activity (GO:0008503)

GO Cellular Component (17): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), dendrite membrane (GO:0032590), neuronal cell body membrane (GO:0032809), chloride channel complex (GO:0034707), presynaptic membrane (GO:0042734), 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), signaling receptor complex (GO:0043235), cell body (GO:0044297), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Neurotransmitter receptors and postsynaptic signal transmission	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
synaptic membrane	3
GABA receptor activity	2
regulation of membrane potential	2
transmitter-gated monoatomic ion channel activity	2
ligand-gated monoatomic ion channel activity	2
synapse	2
behavioral defense response	1
fear response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell-cell signaling	1
learning	1
chemical synaptic transmission	1
neuron development	1
inner ear receptor cell differentiation	1
nerve development	1
multicellular organismal process	1
inner ear development	1
anatomical structure development	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
neuron differentiation	1
cell development	1
chloride channel activity	1
ligand-gated monoatomic anion channel activity	1
molecular transducer activity	1
signaling receptor binding	1
presynaptic membrane	1
regulation of presynaptic membrane potential	1

Protein interactions and networks

STRING

1896 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRA5	SLC6A1	P30531	857
GABRA5	SLC6A13	Q9NSD5	811
GABRA5	SLC6A11	P48066	736
GABRA5	UBE3A	P78355	736
GABRA5	GABBR1	Q9UBS5	641
GABRA5	ATP10A	O60312	609
GABRA5	GABBR2	O75899	585
GABRA5	MKRN3	Q13064	571
GABRA5	SNRPN	P14648	571
GABRA5	MECP2	P51608	560
GABRA5	MAGEL2	Q9UJ55	555
GABRA5	CFAP74	Q9C0B2	545
GABRA5	GAD1	Q99259	536
GABRA5	GRIA3	P42263	535
GABRA5	SCN1A	P35498	524

IntAct

4 interactions, top by confidence:

A	B	Type	Score
GABRA3	HLA-C	psi-mi:“MI:0914”(association)	0.530
GABRB3	GABRA5	psi-mi:“MI:0407”(direct interaction)	0.360
GABRA3	GPAA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): GABRA5 (Affinity Capture-MS), GABRA5 (Proximity Label-MS), GABRA5 (Proximity Label-MS), GABRA5 (Proximity Label-MS), GABRA5 (Proximity Label-MS), GABRA5 (Proximity Label-MS), GABRA5 (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

2 interactions.

A	Effect	B	Mechanism
GABRA5	“form complex”	“GABA-A (a5-b1-g2) receptor”	binding
PCDH19	“up-regulates quantity by stabilization”	GABRA5	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	1
Uncertain significance	78
Likely benign	32
Benign	12

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1456510	NC_000015.9:g.(?26792940)(28544682_?)del	Pathogenic
395546	GRCh37/hg19 15q11.2-13.1(chr15:23707452-28406650)x1	Pathogenic
441588	GRCh37/hg19 15q11.2-13.1(chr15:22770421-29062203)x1	Pathogenic
443863	GRCh37/hg19 15q11.2-13.1(chr15:23615769-28561097)x3	Pathogenic
625713	GRCh37/hg19 15q11.2-13.1(chr15:22770994-29050198)	Pathogenic
689391	NM_000810.4(GABRA5):c.880G>C (p.Val294Leu)	Pathogenic
689392	NM_000810.4(GABRA5):c.880G>T (p.Val294Phe)	Pathogenic
689393	NM_000810.4(GABRA5):c.1238C>T (p.Ser413Phe)	Pathogenic
1207653	NM_000810.4(GABRA5):c.871G>C (p.Val291Leu)	Likely pathogenic

SpliceAI

2077 predictions. Top by Δscore:

Variant	Effect	Δscore
15:26869173:A:AG	acceptor_gain	1.0000
15:26869174:G:GG	acceptor_gain	1.0000
15:26869260:A:T	donor_gain	1.0000
15:26880841:A:AG	acceptor_gain	1.0000
15:26880842:A:G	acceptor_gain	1.0000
15:26880843:A:G	acceptor_gain	1.0000
15:26880844:A:AG	acceptor_gain	1.0000
15:26880845:G:GG	acceptor_gain	1.0000
15:26880845:GC:G	acceptor_gain	1.0000
15:26880845:GCT:G	acceptor_gain	1.0000
15:26880845:GCTT:G	acceptor_gain	1.0000
15:26880845:GCTTT:G	acceptor_gain	1.0000
15:26880963:GGGAG:G	donor_gain	1.0000
15:26880964:GGAG:G	donor_gain	1.0000
15:26880964:GGAGG:G	donor_gain	1.0000
15:26880965:GAG:G	donor_gain	1.0000
15:26880965:GAGG:G	donor_gain	1.0000
15:26880966:AGGTG:A	donor_loss	1.0000
15:26880968:G:GG	donor_gain	1.0000
15:26880968:GT:G	donor_loss	1.0000
15:26880969:T:G	donor_loss	1.0000
15:26883233:GGTA:G	donor_loss	1.0000
15:26883234:GTAG:G	donor_loss	1.0000
15:26883332:A:AG	acceptor_gain	1.0000
15:26883332:ACTAG:A	acceptor_gain	1.0000
15:26883333:C:G	acceptor_gain	1.0000
15:26883333:CTA:C	acceptor_loss	1.0000
15:26883334:TAG:T	acceptor_loss	1.0000
15:26883335:A:AG	acceptor_gain	1.0000
15:26883335:AG:A	acceptor_gain	1.0000

AlphaMissense

3066 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:26880926:T:C	L56P	1.000
15:26880940:G:C	D61H	1.000
15:26880950:T:C	L64P	1.000
15:26880956:C:A	P66H	1.000
15:26883199:T:A	V81D	1.000
15:26883210:G:C	G85R	1.000
15:26883211:G:A	G85D	1.000
15:26883233:G:A	M92I	1.000
15:26883233:G:C	M92I	1.000
15:26883233:G:T	M92I	1.000
15:26883362:G:C	R101P	1.000
15:26883365:A:C	Q102P	1.000
15:26883370:T:A	W104R	1.000
15:26883370:T:C	W104R	1.000
15:26883371:G:C	W104S	1.000
15:26883372:G:C	W104C	1.000
15:26883372:G:T	W104C	1.000
15:26883376:G:C	D106H	1.000
15:26883376:G:T	D106Y	1.000
15:26883377:A:C	D106A	1.000
15:26883377:A:T	D106V	1.000
15:26883383:G:C	R108T	1.000
15:26883383:G:T	R108M	1.000
15:26883384:G:C	R108S	1.000
15:26883384:G:T	R108S	1.000
15:26883386:T:A	L109H	1.000
15:26883386:T:C	L109P	1.000
15:26883391:T:C	F111L	1.000
15:26883393:T:A	F111L	1.000
15:26883393:T:G	F111L	1.000

dbSNP variants (sampled 300 via entrez): RS1000053755 (15:26927019 A>G), RS1000059583 (15:26934116 G>A,T), RS1000066454 (15:26902859 A>C), RS1000066966 (15:26931739 G>A), RS1000152265 (15:26908667 A>G), RS1000183816 (15:26908939 G>C), RS1000197103 (15:26865916 A>G), RS1000201059 (15:26889647 T>C), RS1000233648 (15:26897205 A>C,G), RS1000248374 (15:26878396 T>C), RS1000331993 (15:26928427 C>T), RS1000413733 (15:26864826 T>TC), RS1000424452 (15:26927902 C>T), RS1000451575 (15:26868701 C>T), RS1000467522 (15:26910128 C>G,T)

Disease associations

OMIM: gene MIM:137142 | disease phenotypes: MIM:618559, MIM:612269, MIM:600131, MIM:181500, MIM:105830, MIM:176270

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 79	Strong	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

Mondo (9): developmental and epileptic encephalopathy, 79 (MONDO:0032813), epilepsy, childhood absence, susceptibility to, 5 (MONDO:0012843), epilepsy, childhood absence, susceptibility to, 1 (MONDO:0020759), schizophrenia (MONDO:0005090), autism spectrum disorder (MONDO:0005258), Angelman syndrome (MONDO:0007113), Prader-Willi syndrome (MONDO:0008300), focal epilepsy (MONDO:0005384), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (5): Childhood absence epilepsy (Orphanet:64280), Angelman syndrome (Orphanet:72), Prader-Willi syndrome (Orphanet:739), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

60 total (30 of 60 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001270	Motor delay
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001315	Reduced tendon reflexes
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001508	Failure to thrive
HP:0001558	Decreased fetal movement

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004904_176	Body mass index	3.000000e-08
GCST008170_3	Thyroglobulin plasma levels	2.000000e-06
GCST009391_2078	Metabolite levels	6.000000e-06
GCST010577_16	Crohn’s disease	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0010050	thyroglobulin measurement
EFO:0010372	phosphatidylcholine 32:0 measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D017204	Angelman Syndrome	C10.228.662.075; C16.131.077.095; C16.131.260.040; C16.320.180.040; C16.320.447.250
D004828	Epilepsies, Partial	C10.228.140.490.360
D011218	Prader-Willi Syndrome	C10.597.606.360.690; C16.131.077.730; C16.131.260.700; C16.320.180.700; C16.320.447.500; C18.654.726.750.500.740
C531619	Happy puppet syndrome (formerly) (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (9): CHEMBL2093872 (PROTEIN COMPLEX GROUP), CHEMBL2094122 (PROTEIN COMPLEX), CHEMBL2109243 (PROTEIN COMPLEX GROUP), CHEMBL2109244 (PROTEIN COMPLEX GROUP), CHEMBL3885576 (PROTEIN COMPLEX), CHEMBL3885577 (PROTEIN COMPLEX), CHEMBL4296057 (PROTEIN COMPLEX), CHEMBL4523641 (PROTEIN COMPLEX), CHEMBL5112 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

27 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 506,110 (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
CHEMBL526	PROPOFOL	4	28,835
CHEMBL661	ALPRAZOLAM	4	130,677
CHEMBL268254	DELORAZEPAM	2	1,308
CHEMBL275638	FLAVONE	2	88,985
CHEMBL287631	PROGABIDE	2	3,853
CHEMBL454095	ABECARNIL	2	566
CHEMBL8260	BAICALEIN	2	8,592
CHEMBL200177	MK-0777	2	87
CHEMBL3647536	DARIGABAT	2	138
CHEMBL366947	BRETAZENIL	2
CHEMBL3681419	BASMISANIL	2
CHEMBL1783282	AZD7325	2
CHEMBL73416	SARIPIDEM	2
CHEMBL273481	MUSCIMOL	1
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1
CHEMBL1783256	AZD6280	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

Most potent curated ligand interactions (10 total), top 10:

Ligand	Action	Affinity	Parameter
CGS8216	Inverse agonist	9.6	pKi
flumazenil	Allosteric modulator	9.22	pKi
[3H]RY80	Binding	9.2	pKd
ZK93423	Partial agonist	8.4	pKi
triazolam	Positive	8.4	pKd
compound 20 [PMID: 35584373]	Negative	8.39	pKd
basmisanil	Negative	8.33	pKi
flunitrazepam	Positive	8.26	pKi
ONO-8590580	Negative	8.1	pKi
alprazolam	Positive	8.0	pEC50

Binding affinities (BindingDB)

927 measured of 938 human assays (946 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-[2-[[3-(5-chloro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-2-hydroxyethyl]pyridine-3-carboxamide	KI	0.1 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[1-[[3-(5-chloro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-2,2,2-trifluoroethyl]pyridine-3-carboxamide	KI	0.2 nM	US-8846719: Isoxazolo-pyridine derivatives
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
3-[7-chloro-8-(trifluoromethyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-6-yl]-4-fluoro-phenol	KI	0.27 nM	US-12344614: Benzodiazepine derivatives as GABA a GAMMA1 PAM
6-[[3-(5-fluoro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide	KI	0.3 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[[3-(5-chloro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-(oxan-4-yl)pyridine-3-carboxamide	KI	0.3 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[[3-(5-chloro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-propan-2-ylpyridine-3-carboxamide	KI	0.3 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[[3-(5-chloro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-cyclopropylpyridine-3-carboxamide	KI	0.3 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[[3-(5-fluoropiperidin-2-yl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-propan-2-ylpyridine-3-carboxamide	KI	0.3 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[[3-(5-chloro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy-cyclopropylmethyl]pyridine-3-carboxamide	KI	0.3 nM	US-8846719: Isoxazolo-pyridine derivatives
3-(6-((3-(4-fluorophenyl)-5-methylisoxazol-4-yl) methoxy)pyridazin-3-yl)-5,6-dihydro- 8H-[1,2,4]triazolo[3,4-c][1,4]oxazine	KI	0.32 nM	US-20250215016: ISOXAZOLE-HETEROCYCLIC DERIVATIVE, PHARMACEUTICAL COMPOSITION AND USE
3-(7,8-dichloro-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-6-yl)-4-fluoro-phenol	KI	0.36 nM	US-12344614: Benzodiazepine derivatives as GABA a GAMMA1 PAM
4-fluoro-3-[(4S)-7,8-dichloro-1,4-dimethyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-6-yl]phenol	KI	0.38 nM	US-12344614: Benzodiazepine derivatives as GABA a GAMMA1 PAM
(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
(5S)-8,9-dichloro-7-(2-fluoro-5-hydroxy-phenyl)-5-methyl-5H-pyrimido[1,2-a][1,4]benzodiazepin-3-one	KI	0.39 nM	US-12344614: Benzodiazepine derivatives as GABA a GAMMA1 PAM
8,9-dichloro-7-(2-fluoro-5-hydroxy-phenyl)-5H-pyrimido[1,2-a][1,4]benzodiazepin-3-one	KI	0.39 nM	US-12344614: Benzodiazepine derivatives as GABA a GAMMA1 PAM
6-[[3-(5-fluoro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-(2-hydroxyethyl)pyridine-3-carboxamide	KI	0.4 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[[3-(5-fluoropiperidin-2-yl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-(oxan-4-yl)pyridine-3-carboxamide	KI	0.4 nM	US-8846719: Isoxazolo-pyridine derivatives
N-(cyclopropylmethyl)-6-[[3-(5-fluoropiperidin-2-yl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridine-3-carboxamide	KI	0.4 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[[3-(4-chloro-2-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-propan-2-ylpyridine-3-carboxamide	KI	0.4 nM	US-8846719: Isoxazolo-pyridine derivatives
[6-[[3-(5-chloro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-3-pyridinyl]-thiomorpholin-4-ylmethanone	KI	0.4 nM	US-8846719: Isoxazolo-pyridine derivatives
3-(7,8-dichloro-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-6-yl)-2,4-difluoro-phenol	KI	0.4 nM	US-12344614: Benzodiazepine derivatives as GABA a GAMMA1 PAM
6-chloro-5-(2-fluoro-5-hydroxy-phenyl)-1-methyl-7-(trifluoromethyl)-3H-1,4-benzodiazepin-2-one	KI	0.44 nM	US-12344614: Benzodiazepine derivatives as GABA a GAMMA1 PAM
8-Bromo-7-oxo-3b,4,5,6-tetrahydro-7H-2,6a,11b-triaza-benzo[g]cyclopenta[e]azulene-3-carboxylic acid tert-butyl ester	KI	0.45 nM
4-(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
6,7-dichloro-5-(2,6-difluoro-3-hydroxy-phenyl)-1-methyl-3H-1,4-benzodiazepin-2-one	KI	0.46 nM	US-12344614: Benzodiazepine derivatives as GABA a GAMMA1 PAM
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
N-ethyl-6-[[3-(5-fluoro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridine-3-carboxamide	KI	0.5 nM	US-8846719: Isoxazolo-pyridine derivatives
N-(2-hydroxyethyl)-6-[(5-methyl-3-piperidin-2-yl-1,2-oxazol-4-yl)methoxy]pyridine-3-carboxamide	KI	0.5 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[[3-(4-chlorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-[(2S)-1-hydroxypropan-2-yl]pyridine-3-carboxamide	KI	0.5 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[[3-(4-chlorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-[(1S,2S)-2-hydroxycyclopentyl]pyridine-3-carboxamide	KI	0.5 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[[3-(5-fluoro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide	KI	0.5 nM	US-8846719: Isoxazolo-pyridine derivatives
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
4-(((6-(6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol- 3-yl)pyridazin-3-yl)oxy)methyl)- 3-(4-fluorophenyl)-5-methylisoxazole	KI	0.54 nM	US-20250215016: ISOXAZOLE-HETEROCYCLIC DERIVATIVE, PHARMACEUTICAL COMPOSITION AND USE
(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
N-cyclopropyl-6-[[3-(5-fluoropiperidin-2-yl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridine-3-carboxamide	KI	0.6 nM	US-8846719: Isoxazolo-pyridine derivatives
[6-[[3-(5-chloropiperidin-3-yl)-5-methyl-1,2-oxazol-4-yl]methoxy]-3-pyridinyl]-(1,1-dioxo-1,4-thiazinan-4-yl)methanone	KI	0.6 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[(5-methyl-3-phenyl-1,2-oxazol-4-yl)methoxy]-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-carboxamide	KI	0.6 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[(5-methyl-3-pyridin-2-yl-1,2-oxazol-4-yl)methoxy]-N-propan-2-ylpyridine-3-carboxamide	KI	0.6 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[1-[[3-(5-chloro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-1-hydroxy-2-methylpropan-2-yl]pyridine-3-carboxamide	KI	0.6 nM	US-8846719: Isoxazolo-pyridine derivatives
6-[[3-(5-fluoro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxymethyl]pyridine-3-carboxamide	KI	0.6 nM	US-8846719: Isoxazolo-pyridine derivatives
[6-[[3-(5-chloro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-3-pyridinyl]-morpholin-4-ylmethanone	KI	0.6 nM	US-8846719: Isoxazolo-pyridine derivatives
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
3-(6-((3-(4-fluorophenyl)-5-methylisoxazol-4-yl) methoxy)pyridazin-3-yl)-6,7-dihydro- 4H-[1,2,3]triazolo[5,1-c][1,4]oxazine	KI	0.6 nM	US-20250215016: ISOXAZOLE-HETEROCYCLIC DERIVATIVE, PHARMACEUTICAL COMPOSITION AND USE
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

ChEMBL bioactivities

1961 potent at pChembl≥5 of 2018 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	Ki	0.08	nM	CHEMBL3144696
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	CHEMBL3681588
9.92	Ki	0.12	nM	CHEMBL199957
9.92	Ki	0.12	nM	CHEMBL4476044
9.92	Ki	0.12	nM	CHEMBL4243764
9.85	Ki	0.14	nM	CHEMBL383677
9.85	Ki	0.14	nM	CHEMBL130609
9.82	Ki	0.15	nM	CHEMBL206587
9.82	Ki	0.15	nM	CHEMBL300615
9.80	IC50	0.16	nM	CHEMBL309517
9.77	Ki	0.17	nM	CHEMBL3144849
9.77	Ki	0.17	nM	CHEMBL299210
9.72	Ki	0.19	nM	CHEMBL361129
9.72	Ki	0.19	nM	CHEMBL206380
9.70	Ki	0.2	nM	CHEMBL178677
9.70	Ki	0.2	nM	MK-0777
9.70	Ki	0.2	nM	CHEMBL381380
9.70	Ki	0.2	nM	CHEMBL3681586
9.70	IC50	0.2	nM	CHEMBL4747460
9.70	Ki	0.2	nM	CHEMBL566181
9.70	Ki	0.2	nM	CHEMBL567243
9.70	Ki	0.2	nM	CHEMBL571466
9.70	Ki	0.2	nM	CHEMBL566189
9.70	Ki	0.2	nM	CHEMBL1079870
9.70	Ki	0.2	nM	CHEMBL1078299
9.70	Ki	0.2	nM	CHEMBL3144841
9.68	Ki	0.21	nM	CHEMBL361114
9.68	Ki	0.21	nM	CHEMBL199689
9.64	Ki	0.23	nM	CHEMBL4303594
9.62	IC50	0.24	nM	CHEMBL79037
9.60	Ki	0.25	nM	CGS-8216
9.59	Ki	0.26	nM	CHEMBL362282
9.59	Ki	0.26	nM	CHEMBL202768
9.59	Ki	0.26	nM	CHEMBL3274851
9.57	Ki	0.27	nM	Ro-154513
9.54	Ki	0.29	nM	CHEMBL360122
9.54	Ki	0.29	nM	CHEMBL133049
9.53	Ki	0.293	nM	CHEMBL133049
9.52	Ki	0.3	nM	CHEMBL203286
9.52	Ki	0.3	nM	CHEMBL3676421
9.52	Ki	0.3	nM	CHEMBL3676424
9.52	Ki	0.3	nM	CHEMBL3676425
9.52	Ki	0.3	nM	CHEMBL3676426
9.52	Ki	0.3	nM	CHEMBL3676436
9.52	Ki	0.3	nM	CHEMBL3681585
9.52	Ki	0.3	nM	CHEMBL4060185
9.52	Ki	0.3	nM	CHEMBL5268764

PubChem BioAssay actives

1496 with measured affinity, of 2734 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-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
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
8-ethynyl-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	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
8-bromo-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-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
2-[3-(7-methylimidazo[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
2-[2-fluoro-5-(7-methyl-8-oxoimidazo[1,2-a]pyrazin-3-yl)phenyl]benzonitrile	262297: Displacement of [3H]Ro-151788 from human recombinant GABA-Aalpha5 receptor plus beta3gamma2	ki	0.0001	uM
8-methoxy-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	ki	0.0002	uM
2-(4-ethynylphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-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	72625: Binding affinity for human GABA-A receptor alpha-5-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
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	1604541: Displacement of [3H]-flumazenil from human GABAA alpha5beta3gamma2 expressed in Ltk cells	ki	0.0002	uM
3-fluoro-2-[2-fluoro-5-(7-methyl-8-oxoimidazo[1,2-a]pyrazin-3-yl)phenyl]benzonitrile	262297: Displacement of [3H]Ro-151788 from human recombinant GABA-Aalpha5 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-tert-butyl-6-[(2-ethyl-1,2,4-triazol-3-yl)methoxy]-3-(2-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine	259132: Displacement of [3H]Ro-151788 from human recombinant GABAA alpha5 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0002	uM
2-[3-[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	0.0002	uM
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	0.0002	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
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
8-chloro-2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	1388021: Displacement of [3H]Ro15-1788 from human GABAA receptor alpha5beta3gamma2 expressed in LTK cells preincubated for 30 secs measured every 15 mins at -60 mV holding potential by two-electrode voltage clamp assay	ki	0.0003	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
tert-butyl 8-methoxy-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
3-phenyl-6-(pyridin-4-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	0.0003	uM
9-[(3,5-dimethylpyrazol-1-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	0.0003	uM
9-[(1-ethylimidazol-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	0.0003	uM
3-phenyl-6-(pyridin-2-ylmethoxy)-[1,2,4]triazolo[3,4-a]phthalazine	1551051: Binding affinity to recombinant human GABA-A alpha5beta3gamma2 receptor expressed in L(tk) cells	ki	0.0003	uM
5-chloro-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(17),3,5,9,11,13,15-heptaene	468635: Displacement of [3H]Flumazenil from cloned human GABA alpha-5-beta-3-gamma-2 receptor expressed in HEK293 cells	ki	0.0003	uM
5-chloro-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	468641: Displacement of [3H]Flumazenil from human GABA alpha-5-beta-3-gamma-2 receptor expressed in insect SF9 cells	ki	0.0003	uM
3-(2,6-difluorophenyl)-5-[4-fluoro-3-(3-fluoro-2-pyridinyl)phenyl]pyridazine	262646: Displacement of [3H]Ro-151788 from recombinant human GABA-Aalpha5 receptor plus beta3gamma2	ki	0.0003	uM
ethyl 15-bromo-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	0.0003	uM
7-bromo-5-(2-fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one	1889909: Displacement of [3H]flunitrazepam from human recombinant alpha5beta2gamma2 GABAA receptor expressed in HEK cell membrane by competitive radioligand binding assay	ki	0.0003	uM
ethyl 4-oxo-5-(pyridin-3-ylmethyl)imidazo[1,5-a]quinoxaline-3-carboxylate	1937104: Displacement of flumazenil from alpha5 GABAA receptor (unknown origin)	ki	0.0003	uM
2-phenyl-3aH-pyrazolo[4,3-c]quinolin-3-one	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	ki	0.0003	uM
ethyl 8-azido-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	72626: In vitro binding affinity for human GABA-A receptor alpha-5-beta-3-gamma-2 subunits expressed in L(tk-) cell membranes	ki	0.0003	uM
2-[3-[4-fluoro-3-(5-fluoro-2-pyridinyl)phenyl]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	0.0004	uM
8-bromo-6-(2-chlorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine	1889909: Displacement of [3H]flunitrazepam from human recombinant alpha5beta2gamma2 GABAA receptor expressed in HEK cell membrane by competitive radioligand binding assay	ki	0.0004	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
bisphenol A	decreases expression, increases methylation	2
sodium arsenite	affects methylation, affects cotreatment, increases abundance, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
trichostatin A	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
imidazenil	affects activity	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, decreases expression, affects cotreatment	1
bisphenol S	affects cotreatment, increases methylation	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Carbamazepine	affects expression	1
Estradiol	affects expression	1
Folic Acid	decreases expression	1
Formaldehyde	increases expression	1
gamma-Aminobutyric Acid	affects reaction, increases activity, affects binding	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methotrexate	decreases expression	1
Progesterone	decreases expression	1
Silicon Dioxide	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1

ChEMBL screening assays

413 unique, capped per target: 352 binding, 57 functional, 3 toxicity, 1 admet

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

4 cell lines: 2 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1JN	PrecisION hGABAA alpha5/beta3/gamma2-HEK	Transformed cell line	Female
CVCL_SP43	HAP1 GABRA5 (-) 1	Cancer cell line	Male
CVCL_SP44	HAP1 GABRA5 (-) 2	Cancer cell line	Male
CVCL_YA47	IDG-HEK293T-GABRA5-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety