GABRA6

Summary

GABRA6 (gamma-aminobutyric acid type A receptor subunit alpha6, HGNC:4080) is a protein-coding gene on chromosome 5q34, encoding Gamma-aminobutyric acid receptor subunit alpha-6 (Q16445). 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.

Source: NCBI Gene 2559 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epilepsy (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 79 total
• Druggable target: yes — 19 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000811

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4080
Approved symbol	GABRA6
Name	gamma-aminobutyric acid type A receptor subunit alpha6
Location	5q34
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000145863
Ensembl biotype	protein_coding
OMIM	137143
Entrez	2559

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000274545, ENST00000517823, ENST00000518888, ENST00000520000, ENST00000521520, ENST00000522269, ENST00000523217, ENST00000523691, ENST00000524220

RefSeq mRNA: 1 — MANE Select: NM_000811 NM_000811

CCDS: CCDS4356

Canonical transcript exons

ENST00000274545 — 9 exons

Exon	Start	End
ENSE00000972682	161688949	161689169
ENSE00000972683	161689254	161689336
ENSE00000972684	161689636	161689779
ENSE00001684196	161690201	161690353
ENSE00002094325	161685721	161686027
ENSE00002107251	161701498	161702592
ENSE00003508612	161686936	161687003
ENSE00003509293	161686230	161686348
ENSE00003579858	161691941	161692200

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 98.62.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6585 / max 454.7775, expressed in 13 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59923	0.3049	9
59928	0.1016	6
59919	0.0892	6
59925	0.0376	4
59922	0.0310	6
59930	0.0224	5
59926	0.0157	4
59929	0.0130	4
59921	0.0125	4
59920	0.0118	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	98.62	gold quality
cerebellar cortex	UBERON:0002129	97.84	gold quality
cerebellar hemisphere	UBERON:0002245	97.78	gold quality
cerebellum	UBERON:0002037	97.65	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.60	gold quality
paraflocculus	UBERON:0005351	95.35	gold quality
pons	UBERON:0000988	86.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.77	gold quality
adult organism	UBERON:0007023	70.21	gold quality
prefrontal cortex	UBERON:0000451	62.31	gold quality
right frontal lobe	UBERON:0002810	61.55	gold quality
Brodmann (1909) area 9	UBERON:0013540	60.00	gold quality
frontal cortex	UBERON:0001870	58.20	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	57.81	gold quality
neocortex	UBERON:0001950	57.20	gold quality
cingulate cortex	UBERON:0003027	56.50	gold quality
anterior cingulate cortex	UBERON:0009835	56.13	gold quality
brain	UBERON:0000955	56.06	gold quality
central nervous system	UBERON:0001017	56.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	55.75	gold quality
stromal cell of endometrium	CL:0002255	54.60	silver quality
spinal cord	UBERON:0002240	54.34	gold quality
cerebral cortex	UBERON:0000956	54.29	gold quality
nucleus accumbens	UBERON:0001882	53.68	gold quality
primary visual cortex	UBERON:0002436	52.91	gold quality
telencephalon	UBERON:0001893	52.76	gold quality
amygdala	UBERON:0001876	51.65	gold quality
putamen	UBERON:0001874	51.23	gold quality
forebrain	UBERON:0001890	50.75	gold quality
caudate nucleus	UBERON:0001873	50.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF1, MYC, NFIA, NFIC, POU2F1, REST, SP1, SP3, TP53, ZBTB17

miRNA regulators (miRDB)

61 targeting GABRA6, 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-4795-3P	100.00	74.62	4024
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3924	100.00	72.09	2394
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-126-5P	100.00	72.71	3180
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3658	99.96	73.87	4379
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-7856-5P	99.75	69.99	2901

Literature-anchored findings (GeneRIF, showing 21)

• These findings support a role for the serotonin transporter and GABA(A) alpha6 subunit in depression-related traits. (PMID:14744464)
• alpha1 and alpha6 subunits immobilize recombinant GABA A receptor in transfected cells (PMID:15196679)
• The T1521C polymorphism in the GABRA6 gene is associated with specific personality characteristics as well as a marked attenuation in hormonal and blood pressure responses to psychological stress. (PMID:15197399)
• GABRA6 expression is regulated by NFI in cerebellar granule neurons (PMID:15466411)
• Findings support a role for GABRA6 (Pro385Ser) in perceived parenting. (PMID:16402352)
• polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene may be associated with the development of alcoholism and the GG genotype of the GABAA alpha1 receptor may cause early onset and a severe type of alcoholism (PMID:16778401)
• Polymorphism not associated with panic disorder. (PMID:17167337)
• Chinese patients with certain psychiatric characteristics and GABRA6 heterozygosity are probably predisposed to functional heartburn (PMID:17295876)
• The T allele of the 1519T>C GABA(A)alpha6 gene may be one of the modulating factors associated with changes in craving for alcohol and food during treatment of patients with alcohol dependence. (PMID:18616664)
• Significant matching effects were found for polymorphisms at the DRD2, GABRA6 and GABRB2 gene. In addition, a trend was found for the OPRM1 polymorphism. (PMID:19523047)
• 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)
• studies have found prefrontal cortical GABA(A) receptor alpha subunit alterations in schizophrenia (PMID:20100621)
• significant involvement of alpha (GABRA6) and beta (GABRB2) subunits of GABA(A) receptor in epilepsy susceptibility in north Indian population (PMID:21420396)
• Part of the interindividual differences observed for anxiety traits measured by the Harm Avoidance dimension could be explained by the GABRA6 gene variability. (PMID:21902679)
• GABRA6 mutation, R46W, was identified as a susceptibility gene that may contribute to the pathogenesis of childhood absence epilepsy and cause neuronal disinhibition and increase in seizures via a reduction of alphabetagamma and alphabetadelta receptor function and expression (PMID:21930603)
• genetic association study in Chinese Han population: Data suggest an SNP in GABRA6 (rs3219151) is associated with decreased predisposition to schizophrenia via alteration of miroRNA binding to target in 3-prime-untranslated region of GABRA6 mRNA. (PMID:23332465)
• The gene-gene interaction at two loci involving GABRA6 and Synapsin II revealed a significant association for development of idiopathic generalized epilepsy. (PMID:25088614)
• TMEM132D, COMT and GABRA6 gene polymorphisms may influence susceptibility to panic disorder(PD) and major depressive disorder(MDD)in Japanese adults; these variants may increase vulnerability to PD by modulating oligodendrocytes and GABA and dopaminergic functions in related brain regions, altering neuronal processing of anxiety-related emotional signals (PMID:25974322)
• NOS3, GABRA6, child abuse, neighborhood crime Gene x Gene, Environment x Environment, and Gene x Environment interactions are associated with different patterns of respiratory sinus arrhythmia reactivity. (PMID:26535938)
• stress-associated suicide risk is elevated in carriers of the GABRA6 rs3219151 T allele with several independent markers and predictors of suicidal behaviours converging to this increased risk. (PMID:29018204)
• GABRA1 and GABRA6 gene mutations in idiopathic generalized epilepsy patients. (PMID:34740144)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabra6b	ENSDARG00000058736
danio_rerio	gabra6a	ENSDARG00000075058
mus_musculus	Gabra6	ENSMUSG00000020428
rattus_norvegicus	Gabra6	ENSRNOG00000003569

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), 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 alpha-6 — Q16445 (reviewed: Q16445)

Alternative names: GABA(A) receptor subunit alpha-6

All UniProt accessions (5): E7EV53, Q16445, H0YAS3, H0YBP3, H0YBS7

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. Alpha-6/GABRA6 subunits 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. Extrasynaptic alpha-6-containing receptors contribute to the tonic GABAergic inhibition. Alpha-6 subunits are also present on glutamatergic synapses.

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. Binds UBQLN1.

Subcellular location. Postsynaptic cell membrane. Cell membrane.

Tissue specificity. Expressed in brain, in cerebellar granule cells.

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. GABRA6 sub-subfamily.

RefSeq proteins (1): NP_000802* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001390	GABAAa_rcpt	Family
IPR005436	GABBAa6_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 (22 total): topological domain 5, transmembrane region 4, glycosylation site 3, sequence variant 3, binding site 2, signal peptide 1, chain 1, modified residue 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16445-F1	82.69	0.64

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): 84; 147

Post-translational modifications (1): 403

Disulfide bonds (1): 156–170

Glycosylation sites (3): 31, 128, 141

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-977443	GABA receptor activation

MSigDB gene sets: 154 (showing top): MYAATNNNNNNNGGC_UNKNOWN, GOBP_SYNAPSE_ASSEMBLY, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, RACCACAR_AML_Q6, GOBP_CELL_CELL_SIGNALING, CDP_01, GOBP_CELL_JUNCTION_ORGANIZATION, MODULE_205, MODULE_289, GOBP_CHLORIDE_TRANSPORT, AML_Q6, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, TGCTGAY_UNKNOWN, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION

GO Biological Process (9): signal transduction (GO:0007165), gamma-aminobutyric acid signaling pathway (GO:0007214), synaptic transmission, GABAergic (GO:0051932), chloride transmembrane transport (GO:1902476), inhibitory synapse assembly (GO:1904862), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220), regulation of postsynaptic membrane potential (GO:0060078)

GO Molecular Function (9): GABA-A receptor activity (GO:0004890), 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), chloride channel activity (GO:0005254), signaling receptor activity (GO:0038023)

GO Cellular Component (10): plasma membrane (GO:0005886), dendrite membrane (GO:0032590), chloride channel complex (GO:0034707), postsynapse (GO:0098794), cerebellar Golgi cell to granule cell synapse (GO:0099192), postsynaptic specialization membrane (GO:0099634), GABA-A receptor complex (GO:1902711), membrane (GO:0016020), 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
GABA receptor activity	2
transmitter-gated monoatomic ion channel activity	2
synapse	2
cellular anatomical structure	2
synaptic membrane	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell-cell signaling	1
chemical synaptic transmission	1
chloride transport	1
monoatomic anion transmembrane transport	1
synapse assembly	1
transport	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
regulation of membrane potential	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
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
molecular transducer activity	1
membrane	1
cell periphery	1
dendrite	1
neuron projection membrane	1
monoatomic ion channel complex	1
postsynaptic membrane	1
postsynaptic specialization	1
GABA receptor complex	1

Protein interactions and networks

STRING

1754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRA6	SLC6A1	P30531	673
GABRA6	CLCN2	P51788	619
GABRA6	SLC6A4	P31645	598
GABRA6	FAT3	Q8TDW7	585
GABRA6	CSMD3	Q7Z407	580
GABRA6	ANKK1	Q8NFD2	571
GABRA6	ADH6	P28332	550
GABRA6	TAS2R16	Q9NYV7	549
GABRA6	SCN1A	P35498	538
GABRA6	SCN1B	Q07699	533
GABRA6	PCP2	Q8IVA1	532
GABRA6	CHRM2	P08172	520
GABRA6	NRXN3	Q9Y4C0	512
GABRA6	CDK12	Q9NYV4	506
GABRA6	COMT	P21964	498

IntAct

24 interactions, top by confidence:

A	B	Type	Score
GABRA6	HMGCR	psi-mi:“MI:0914”(association)	0.350
AKT1	GABRA6	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	GABRA6	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	GABRA6	psi-mi:“MI:2364”(proximity)	0.270
GABRA6	SMARCA4	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	GABRA6	psi-mi:“MI:2364”(proximity)	0.270
SPOP	GABRA6	psi-mi:“MI:2364”(proximity)	0.270
GABRA6	SPOP	psi-mi:“MI:2364”(proximity)	0.270
GABRA6	PTEN	psi-mi:“MI:2364”(proximity)	0.270
GABRA6	PTPN11	psi-mi:“MI:2364”(proximity)	0.270
GABRA6	TP53	psi-mi:“MI:2364”(proximity)	0.270
GABRA6	BRAF	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (21): GABRB3 (Affinity Capture-MS), EHD2 (Affinity Capture-MS), ZMYND19 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), PDZD8 (Affinity Capture-MS), HMGCR (Affinity Capture-MS), BSCL2 (Affinity Capture-MS), ST7L (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), DNAJC18 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), DNAJC18 (Affinity Capture-MS), EHD2 (Affinity Capture-MS), ZMYND19 (Affinity Capture-MS), GABRB3 (Affinity Capture-MS)

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

Diamond homologs: 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

4 interactions.

A	Effect	B	Mechanism
GABRA6	“form complex”	“GABA-A (a6-b1-g2) receptor”	binding
GABRA6	“form complex”	“GABA-A (a6-b2-d) receptor”	binding
GABRA6	“form complex”	“GABA-A (a6-b3-d) receptor”	binding
PCDH19	“up-regulates quantity by stabilization”	GABRA6	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	19
Benign	12

Top pathogenic / likely-pathogenic (0)

SpliceAI

1732 predictions. Top by Δscore:

Variant	Effect	Δscore
5:161686345:GGAG:G	donor_gain	1.0000
5:161686346:GAG:G	donor_gain	1.0000
5:161686346:GAGG:G	donor_gain	1.0000
5:161686347:AGGT:A	donor_loss	1.0000
5:161686348:GGTA:G	donor_loss	1.0000
5:161686349:G:GG	donor_gain	1.0000
5:161686349:GT:G	donor_loss	1.0000
5:161686350:T:G	donor_loss	1.0000
5:161686923:G:A	acceptor_gain	1.0000
5:161687000:GATG:G	donor_gain	1.0000
5:161687001:ATGG:A	donor_loss	1.0000
5:161687004:G:GG	donor_gain	1.0000
5:161687005:T:TC	donor_loss	1.0000
5:161687006:GA:G	donor_gain	1.0000
5:161687008:G:GG	donor_gain	1.0000
5:161687887:A:T	donor_gain	1.0000
5:161688700:G:GT	donor_gain	1.0000
5:161688714:A:T	donor_gain	1.0000
5:161688733:G:GT	donor_gain	1.0000
5:161688948:GGA:G	acceptor_gain	1.0000
5:161689332:GAGCT:G	donor_gain	1.0000
5:161689334:GCT:G	donor_gain	1.0000
5:161689337:G:GG	donor_gain	1.0000
5:161689626:A:AG	acceptor_gain	1.0000
5:161689635:GAT:G	acceptor_gain	1.0000
5:161689776:ACAGG:A	donor_loss	1.0000
5:161689778:AGGTA:A	donor_loss	1.0000
5:161689779:GGTAA:G	donor_loss	1.0000
5:161689781:T:A	donor_loss	1.0000
5:161691939:A:AG	acceptor_gain	1.0000

AlphaMissense

2979 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:161688974:G:C	R84P	1.000
5:161688977:A:C	Q85P	1.000
5:161688982:T:A	W87R	1.000
5:161688982:T:C	W87R	1.000
5:161688984:G:C	W87C	1.000
5:161688984:G:T	W87C	1.000
5:161689057:T:A	W112R	1.000
5:161689057:T:C	W112R	1.000
5:161689059:G:C	W112C	1.000
5:161689059:G:T	W112C	1.000
5:161689064:C:A	P114H	1.000
5:161689148:G:T	G142V	1.000
5:161689256:T:C	L150P	1.000
5:161689273:T:A	C156S	1.000
5:161689273:T:C	C156R	1.000
5:161689274:G:A	C156Y	1.000
5:161689274:G:C	C156S	1.000
5:161689275:T:G	C156W	1.000
5:161689294:T:C	F163L	1.000
5:161689295:T:G	F163C	1.000
5:161689296:T:A	F163L	1.000
5:161689296:T:G	F163L	1.000
5:161689297:C:T	P164S	1.000
5:161689298:C:A	P164H	1.000
5:161689315:T:C	C170R	1.000
5:161689322:T:C	L172P	1.000
5:161689333:A:C	S176R	1.000
5:161689335:C:A	S176R	1.000
5:161689335:C:G	S176R	1.000
5:161689668:T:A	W188R	1.000

dbSNP variants (sampled 300 via entrez): RS1000050924 (5:161696868 C>T), RS1000915049 (5:161690801 T>C), RS1001136032 (5:161688635 T>A), RS1001389461 (5:161701210 A>T), RS1001538723 (5:161693597 A>G), RS1001771326 (5:161687530 A>T), RS1001887112 (5:161692146 A>G), RS1002028394 (5:161685747 G>A,C), RS1002097770 (5:161687171 T>C), RS1002443890 (5:161698418 C>G,T), RS1002505258 (5:161686184 T>C), RS1002540206 (5:161695152 C>G), RS1002593842 (5:161695439 A>G), RS1002800057 (5:161697989 G>A,C), RS1003107826 (5:161700859 G>A,C)

Disease associations

OMIM: gene MIM:137143 | disease phenotypes: MIM:600131

GenCC curated gene-disease

Disease	Classification	Inheritance
epilepsy	Limited	Autosomal dominant

Mondo (2): childhood absence epilepsy (MONDO:0010826), epilepsy (MONDO:0005027)

Orphanet (1): Childhood absence epilepsy (Orphanet:64280)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012490_384	Femur bone mineral density x serum urate levels interaction	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2093872 (PROTEIN COMPLEX GROUP), CHEMBL2095190 (PROTEIN COMPLEX), CHEMBL2109243 (PROTEIN COMPLEX GROUP), CHEMBL2109244 (PROTEIN COMPLEX GROUP), CHEMBL2111370 (PROTEIN COMPLEX), CHEMBL2579 (SINGLE PROTEIN), CHEMBL3885578 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 556,267 (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
CHEMBL15891	LINDANE	4	83,653
CHEMBL526	PROPOFOL	4	28,835
CHEMBL268254	DELORAZEPAM	2	1,308
CHEMBL275638	FLAVONE	2	88,985
CHEMBL287631	PROGABIDE	2	3,853
CHEMBL454095	ABECARNIL	2	566
CHEMBL8260	BAICALEIN	2	8,592
CHEMBL366947	BRETAZENIL	2	818
CHEMBL279867	PANADIPLON	2	312
CHEMBL273481	MUSCIMOL	1	5,759
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1	160,188

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1992647	Efficacy	3	antidepressants;Selective serotonin reuptake inhibitors;venlafaxine	Major Depressive Disorder

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1992647	GABRA6	3	0.00	1	antidepressants;Selective serotonin reuptake inhibitors;venlafaxine
rs3219151	GABRA6		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
CGS8216	Inverse agonist	7.77	pKi
flumazenil	Partial agonist	6.83	pKi
cenobamate	Positive	4.24	pEC50

Binding affinities (BindingDB)

20 measured of 22 human assays (31 total across all organisms); most potent 20 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(4-Methoxy-phenyl)-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one (CGS 9895)	KI	0.09 nM
CGS 9896	KI	0.26 nM
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
Halcion	KI	0.68 nM
FG 8205	KI	0.68 nM
RO-154513	KI	10 nM
NSC_104999	KI	11.2 nM
ethyl 12-ethynyl-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,10,12-pentaene-5-carboxylate	KI	28.4 nM
P4S	KI	151 nM
CAS_4375	KI	160 nM
5-({12-ethynyl-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,10,12-pentaen-5-yl}carbonyloxy)pentyl 12-ethynyl-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,11,13-pentaene-5-carboxylate	KI	231 nM
3-({12-ethynyl-9-phenyl-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,8,10,12-hexaen-5-yl}carbonyloxy)propyl 12-ethynyl-9-phenyl-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaene-5-carboxylate	KI	236 nM
CAS_5448	KI	240 nM
ethyl 12-ethynyl-9-phenyl-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaene-5-carboxylate	KI	287 nM
4-[6-Amino-3-(4-methoxy-phenyl)-6H-pyridazin-1-yl]-butyric acid : bromide	KI	316 nM
2-[2-({12-ethynyl-9-phenyl-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,8,10,12-hexaen-5-yl}carbonyloxy)ethoxy]ethyl 12-ethynyl-9-phenyl-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaene-5-carboxylate	KI	460 nM
CAS_64603-91-4	KI	1620 nM
Thio-4-PIOL	KI	1700 nM
3-({12-ethyl-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,10,12-pentaen-5-yl}carbonyloxy)propyl 12-ethyl-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,11,13-pentaene-5-carboxylate	KI	1850 nM
DIAZEPAM	IC50	5600 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof

ChEMBL bioactivities

724 potent at pChembl≥5 of 773 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL454349
9.80	IC50	0.16	nM	CHEMBL309517
9.70	IC50	0.2	nM	CHEMBL4747460
9.62	IC50	0.24	nM	CHEMBL79037
9.40	IC50	0.3981	nM	CGS-8216
9.40	IC50	0.4	nM	CHEMBL1271047
9.34	IC50	0.46	nM	CHEMBL78730
9.31	IC50	0.49	nM	CHEMBL76263
9.30	IC50	0.5	nM	CHEMBL5266498
9.30	IC50	0.5	nM	CHEMBL5290464
9.30	IC50	0.5	nM	CHEMBL5280240
9.30	IC50	0.5	nM	CHEMBL49141
9.30	IC50	0.5	nM	CHEMBL1518572
9.22	IC50	0.6026	nM	CGS-9896
9.22	IC50	0.6	nM	CHEMBL419096
9.12	IC50	0.76	nM	CHEMBL540583
9.10	IC50	0.79	nM	CHEMBL77226
9.10	IC50	0.8	nM	CHEMBL5265845
9.10	IC50	0.8	nM	CHEMBL5291368
9.10	IC50	0.8	nM	CHEMBL5271392
9.07	Ki	0.85	nM	CLONAZEPAM
9.05	Ki	0.9	nM	FLUMAZENIL
9.05	IC50	0.9	nM	CHEMBL5285377
9.00	Ki	1	nM	CHEMBL3410222
9.00	IC50	1	nM	BETA-CCM
9.00	IC50	1	nM	CHEMBL454606
9.00	IC50	1	nM	CHEMBL1337028
9.00	IC50	1	nM	CHEMBL509197
9.00	IC50	1	nM	ABECARNIL
9.00	Ki	1	nM	CHEMBL54341
9.00	Ki	1	nM	CHEMBL348367
8.96	IC50	1.1	nM	CHEMBL444586
8.89	IC50	1.3	nM	LINDANE
8.77	Ki	1.7	nM	CHEMBL154342
8.74	IC50	1.8	nM	CHEMBL444050
8.72	Ki	1.9	nM	CHEMBL4060185
8.70	IC50	2	nM	MUSCIMOL
8.69	Ki	2.03	nM	CHEMBL3144617
8.66	IC50	2.2	nM	CHEMBL80610
8.64	IC50	2.3	nM	FIPRONIL
8.55	IC50	2.8	nM	CHEMBL75642
8.55	Ki	2.8	nM	CHEMBL372281
8.55	IC50	2.8	nM	DELORAZEPAM
8.52	Ki	3	nM	CHEMBL265547
8.52	IC50	3	nM	CHEMBL510764
8.52	IC50	3	nM	CHEMBL5266558
8.52	IC50	3	nM	CHEMBL2262044
8.52	IC50	3	nM	CHEMBL499814
8.52	IC50	3	nM	CHEMBL1161036
8.51	IC50	3.1	nM	FIPRONIL

PubChem BioAssay actives

649 with measured affinity, of 1422 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
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
ethyl 4-methyl-5-propan-2-yloxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0004	uM
2-phenyl-3aH-pyrazolo[4,3-c]quinolin-3-one	40988: Inhibition on Benzodiazepine receptor	ic50	0.0004	uM
ethyl 4-(methoxymethyl)-6-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
ethyl 4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
ethyl 6-methoxy-4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
ethyl 4-(methoxymethyl)-6-propoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
ethyl 6-hydroxy-4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
2-(4-chlorophenyl)-3aH-pyrazolo[4,3-c]quinolin-3-one	40988: Inhibition on Benzodiazepine receptor	ic50	0.0006	uM
5-[[3-(1,3-benzodioxol-5-yl)-6-iminopyridazin-1-yl]methyl]-1,2-thiazol-3-one;hydrobromide	72153: Affinity for gamma-aminobutyric-acid A receptor measured by its ability to displace [3H]gabazine antagonist from rat brain preparations.	ic50	0.0008	uM
propan-2-yl 16-(methoxymethyl)-3,6,11,14-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-1(10),2,4,6,8,12,14,16-octaene-15-carboxylate	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0008	uM
propan-2-yl 4-(methoxymethyl)-6,9,14,21-tetrazapentacyclo[11.8.0.02,10.03,8.015,20]henicosa-1(21),2,4,6,8,10,12,15(20)-octaene-5-carboxylate	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0008	uM
propan-2-yl 15-(methoxymethyl)-4-propan-2-yl-5-oxa-10,13-diazatetracyclo[7.7.0.02,6.011,16]hexadeca-1(9),2(6),3,7,11,13,15-heptaene-14-carboxylate	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0008	uM
Clonazepam	239299: Displacement of [3H]flumazenil from bovine benzodiazepine receptor GABA-A channel of brain membranes	ki	0.0008	uM
15-(methoxymethyl)-14-(5-methyl-1,2-oxazol-3-yl)-4-propan-2-yl-5-oxa-3,10,13-triazatetracyclo[7.7.0.02,6.011,16]hexadeca-1(9),2(6),3,7,11,13,15-heptaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0009	uM
Flumazenil	239299: Displacement of [3H]flumazenil from bovine benzodiazepine receptor GABA-A channel of brain membranes	ki	0.0009	uM
ethyl 9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0010	uM
methyl 9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0010	uM
propyl 9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0010	uM
tert-butyl 9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0010	uM
7-chloro-5-methyl-3-(2-phenylethynyl)-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one	1196597: Displacement of [3H]flumazenil from rat cortex GABAA receptor BDZ binding site expressed in HEK293 cells by competition binding assay	ki	0.0010	uM
6-bromo-2-(3-nitrophenyl)chromen-4-one	72729: Binding affinity towards benzodiazepine site in GABAA receptor	ki	0.0010	uM
(2-methoxyphenyl)methyl 8-chloro-5-oxido-3,3a-dihydropyrazolo[5,1-c][1,2,4]benzotriazin-5-ium-3-carboxylate	41860: Binding affinity towards Benzodiazepine receptor from bovine brain membrane using [3H]Ro-151788 as radioligand	ki	0.0010	uM
propan-2-yl 4-(methoxymethyl)-6-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0010	uM
(2-methoxyphenyl)methyl 8-chloropyrazolo[5,1-c][1,2,4]benzotriazine-3-carboxylate	41860: Binding affinity towards Benzodiazepine receptor from bovine brain membrane using [3H]Ro-151788 as radioligand	ki	0.0017	uM
8-chloro-2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	1388022: Displacement of [3H]Ro15-1788 from human GABAA receptor alpha6beta3gamma2 expressed in LTK cells preincubated for 30 secs measured every 15 mins at -60 mV holding potential by two-electrode voltage clamp assay	ki	0.0019	uM
7-methoxy-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	71266: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-6-beta-3-gamma-2	ki	0.0020	uM
5-(aminomethyl)-1,2-oxazol-3-one	72155: Binding affinity in vivo for gamma-aminobutyric-acid A receptor measured by its ability to displace [3H]-GABA agonist from rat brain preparations after iv injection.	ic50	0.0020	uM
Fipronil	242615: In vitro insecticidal activity as inhibition of [3H]EBOB binding to Gamma-aminobutyric acid GABA-A receptor of housefly neuronal membranes	ic50	0.0023	uM
9-chloro-2-phenyl-6H-triazolo[1,2-a][1,2,4]benzotriazine-1,5-dione	239299: Displacement of [3H]flumazenil from bovine benzodiazepine receptor GABA-A channel of brain membranes	ki	0.0028	uM
7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one	40974: In vitro displacement of [3H]-diazepam from GABA-A Benzodiazepine receptor	ic50	0.0028	uM
3-isothiocyanato-9H-pyrido[3,4-b]indole	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0030	uM
9H-pyrido[3,4-b]indole-3-carbonitrile	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0030	uM
3-(6,7-difluoro-1,3-benzoxazol-2-yl)-1,3a,4,5,6,7,8,8a-octahydrocyclohepta[d]imidazol-2-one	40986: Binding affinity against GABA-A benzodiazepine receptor	ki	0.0030	uM
(5aR,7R,9aS,11aS)-2-amino-7-hydroxy-9a,11a-dimethyl-3,3a,3b,4,5,5a,6,7,8,9,9b,11-dodecahydronaphtho[2,1-e]indol-10-one	72153: Affinity for gamma-aminobutyric-acid A receptor measured by its ability to displace [3H]gabazine antagonist from rat brain preparations.	ic50	0.0030	uM
3-propoxy-9H-pyrido[3,4-b]indole	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0030	uM
1-(9H-pyrido[3,4-b]indol-3-yl)butan-1-one	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0030	uM
ethyl 8-azido-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	71266: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-6-beta-3-gamma-2	ki	0.0038	uM
8-fluoro-5-methyl-3-(2-phenylethynyl)-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one	1196597: Displacement of [3H]flumazenil from rat cortex GABAA receptor BDZ binding site expressed in HEK293 cells by competition binding assay	ki	0.0040	uM
methyl 6-hydroxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0040	uM
2-phenyl-6H-[1,2,4]triazolo[1,5-c]quinazolin-5-one	40986: Binding affinity against GABA-A benzodiazepine receptor	ki	0.0040	uM
17-chloro-9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0040	uM
5-nitro-9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0040	uM
5-bromo-9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0040	uM
17-methoxy-9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0040	uM
tert-butyl 8-chloro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	71266: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-6-beta-3-gamma-2	ki	0.0040	uM
9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0040	uM
8-bromo-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	71266: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-6-beta-3-gamma-2	ki	0.0040	uM
methyl 6-(benzylamino)-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0040	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
gamma-Aminobutyric Acid	affects binding, increases activity, increases reaction, decreases reaction	3
Benzo(a)pyrene	increases expression, increases methylation	2
sodium arsenate	decreases expression, increases abundance	1
tetramethylenedisulfotetramine	increases activity, increases response to substance, affects binding, decreases reaction	1
picrotoxinin	decreases reaction, increases activity, affects binding	1
Ro 15-4513	affects binding, increases activity, increases reaction	1
bretazenil	affects binding, increases activity	1
L 663581	affects binding, increases activity	1
fipronil	affects binding, decreases activity	1
delta-hexachlorocyclohexane	increases reaction, affects binding, increases activity	1
2-palmitoylglycerol	increases expression	1
Acamprosate	affects response to substance	1
Felbamate	affects binding, decreases activity	1
Acetaminophen	increases expression	1
Arsenic	decreases expression, increases abundance	1
Hexachlorocyclohexane	affects binding, decreases reaction, increases activity	1
Bicuculline	affects binding, decreases activity	1
Cadmium	decreases expression	1
Carbamazepine	affects expression	1
Carmustine	decreases expression	1
Flumazenil	affects binding, increases activity, increases reaction	1
Mercury	increases expression	1
Midazolam	decreases response to substance	1
Naltrexone	affects response to substance	1
Pregnanolone	affects binding, increases activity	1
Tetrachlorodibenzodioxin	increases expression	1
Propofol	affects binding, increases activity	1
Aflatoxin B1	decreases methylation	1
GABA Agents	affects binding, increases activity	1

ChEMBL screening assays

264 unique, capped per target: 227 binding, 33 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

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1JP	PrecisION hGABAA alpha6/beta3/gamma2-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

310 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