GABRQ

Summary

GABRQ (gamma-aminobutyric acid type A receptor subunit theta, HGNC:14454) is a protein-coding gene on chromosome Xq28, encoding Gamma-aminobutyric acid receptor subunit theta (Q9UN88). Theta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes the theta subunit of the GABA A receptor. The gene is mapped to chromosome Xq28 in a cluster of genes including those that encode the alpha 3 and epsilon subunits of the GABA A receptor.

Source: NCBI Gene 55879 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 94 total
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_018558

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14454
Approved symbol	GABRQ
Name	gamma-aminobutyric acid type A receptor subunit theta
Location	Xq28
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000268089
Ensembl biotype	protein_coding
OMIM	300349
Entrez	55879

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000598523

RefSeq mRNA: 1 — MANE Select: NM_018558 NM_018558

CCDS: CCDS14707

Canonical transcript exons

ENST00000598523 — 9 exons

Exon	Start	End
ENSE00002977626	152640378	152640466
ENSE00003003037	152650428	152650580
ENSE00003019998	152651526	152651782
ENSE00003070943	152637895	152638351
ENSE00003114752	152646948	152647168
ENSE00003129640	152645527	152645594
ENSE00003165516	152649742	152649879
ENSE00003186348	152652541	152657542
ENSE00003218910	152649251	152649333

Expression profiles

Bgee: expression breadth broad, 82 present calls, max score 76.41.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7121 / max 134.1467, expressed in 535 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198003	2.7121	535

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hypothalamus	UBERON:0001898	76.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.59	gold quality
tibialis anterior	UBERON:0001385	69.58	silver quality
anterior cingulate cortex	UBERON:0009835	68.14	gold quality
amygdala	UBERON:0001876	68.09	gold quality
cingulate cortex	UBERON:0003027	68.08	gold quality
Ammon’s horn	UBERON:0001954	68.01	gold quality
superior vestibular nucleus	UBERON:0007227	66.10	silver quality
pancreatic ductal cell	CL:0002079	65.45	silver quality
ectocervix	UBERON:0012249	64.23	gold quality
endocervix	UBERON:0000458	64.08	gold quality
prefrontal cortex	UBERON:0000451	63.53	gold quality
nucleus accumbens	UBERON:0001882	63.11	gold quality
buccal mucosa cell	CL:0002336	62.93	gold quality
temporal lobe	UBERON:0001871	61.45	gold quality
ileal mucosa	UBERON:0000331	60.35	silver quality
ventricular zone	UBERON:0003053	59.92	gold quality
lateral nuclear group of thalamus	UBERON:0002736	59.71	gold quality
cerebral cortex	UBERON:0000956	59.10	gold quality
neocortex	UBERON:0001950	58.77	gold quality
cortical plate	UBERON:0005343	58.77	silver quality
uterine cervix	UBERON:0000002	58.62	gold quality
gingival epithelium	UBERON:0001949	58.51	silver quality
deltoid	UBERON:0001476	58.30	silver quality
tibial nerve	UBERON:0001323	58.29	gold quality
telencephalon	UBERON:0001893	57.69	gold quality
ganglionic eminence	UBERON:0004023	57.46	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	57.02	gold quality
frontal cortex	UBERON:0001870	56.86	gold quality
forebrain	UBERON:0001890	56.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.10

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 8)

• Although GABRQ genes did not show positive association, further studies are necessary to consider the role of other GABA receptor genes in migraine susceptibility (PMID:19087248)
• single nucleotide polymorphisms studied in the GABRA4, GABRE, and GABRQ genes are not related to the risk for familial ET. (PMID:21422964)
• GABRQ plays important roles in hepatocellular carcinoma development and progression (PMID:22690081)
• We identified truncating mutations in distinct X-linked gamma-aminobutyric acid A (GABAA) receptor subunit-encoding genes, GABRQ and GABRA3.this is the first report of ASD patients with truncating mutations in GABA receptors genes. (PMID:23169495)
• data from the present study suggest a possible role of GABRQ rs3810651 single nucleotide polymorphism in the modification of the age at onset of migraine in the Caucasian Spanish people (PMID:29299688)
• The intracellular domain of GABRQ disrupts GABRB3 homomeric plasma membrane expression. (PMID:31610743)
• A pioneering study indicate role of GABRQ rs3810651 in ASD severity of Indo-Caucasoid female probands. (PMID:33772085)
• The severity of behavioural symptoms in FTD is linked to the loss of GABRQ-expressing VENs and pyramidal neurons. (PMID:35152451)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gabrq	ENSMUSG00000031344
rattus_norvegicus	Gabrq	ENSRNOG00000053402

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 theta — Q9UN88 (reviewed: Q9UN88)

Alternative names: GABA(A) receptor subunit theta

All UniProt accessions (1): Q9UN88

UniProt curated annotations — full annotation on UniProt →

Function. Theta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain. GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interfaces. When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient.

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.

Tissue specificity. Expressed in brain.

Activity regulation. Potentiated by etomidate, propofol, pregnanolone and pentobarbital.

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. GABRQ sub-subfamily.

RefSeq proteins (1): NP_061028* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006028	GABAA/Glycine_rcpt	Family
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR008101	GABAAt_rcpt	Family
IPR018000	Neurotransmitter_ion_chnl_CS	Conserved_site
IPR036719	Neuro-gated_channel_TM_sf	Homologous_superfamily
IPR036734	Neur_chan_lig-bd_sf	Homologous_superfamily
IPR038050	Neuro_actylchol_rec	Homologous_superfamily

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (20 total): compositionally biased region 4, topological domain 4, transmembrane region 4, region of interest 2, sequence variant 2, signal peptide 1, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UN88-F1	67.55	0.34

Functional residue map

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

Disulfide bonds (1): 183–197

Glycosylation sites (1): 127

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 92 (showing top): GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, GOBP_CELL_CELL_SIGNALING, MYOD_01, GOBP_CHLORIDE_TRANSPORT, BLALOCK_ALZHEIMERS_DISEASE_UP, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, OCT1_06, GOBP_SYNAPTIC_SIGNALING, REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES, GCM_CDH5, RIGGI_EWING_SARCOMA_PROGENITOR_UP, GOBP_TRANSMEMBRANE_TRANSPORT, TGGAAA_NFAT_Q4_01

GO Biological Process (7): signal transduction (GO:0007165), synaptic transmission, GABAergic (GO:0051932), chloride transmembrane transport (GO:1902476), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), neurotransmitter transport (GO:0006836), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (8): transmembrane signaling receptor activity (GO:0004888), GABA-A receptor activity (GO:0004890), neurotransmitter transmembrane transporter activity (GO:0005326), GABA-gated chloride ion channel activity (GO:0022851), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), chloride channel activity (GO:0005254), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), chloride channel complex (GO:0034707), signaling receptor complex (GO:0043235), postsynaptic membrane (GO:0045211), GABA-A receptor complex (GO:1902711), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
chemical synaptic transmission	1
chloride transport	1
monoatomic anion transmembrane transport	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
signaling receptor activity	1
GABA receptor activity	1
neurotransmitter transport	1
transmembrane transporter activity	1
chloride channel activity	1
transmitter-gated monoatomic ion channel activity	1
ligand-gated monoatomic anion channel 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
binding	1
membrane	1
cell periphery	1
monoatomic ion channel complex	1
protein-containing complex	1
synaptic membrane	1
postsynapse	1
GABA receptor complex	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

1008 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRQ	PRLHR	P49683	533
GABRQ	ADRA1A	P35348	508
GABRQ	GABBR2	O75899	482
GABRQ	FEZF2	Q8TBJ5	460
GABRQ	TMEM215	Q68D42	452
GABRQ	TH	P07101	450
GABRQ	GABRG2	P18507	434
GABRQ	BRS3	P32247	433
GABRQ	GABRR2	P28476	408
GABRQ	DRD3	P35462	407
GABRQ	GABRG3	Q99928	396
GABRQ	ATF3	P18847	376
GABRQ	SLC6A1	P30531	376
GABRQ	GALNT17	Q6IS24	374
GABRQ	GPR139	Q6DWJ6	370

IntAct

7 interactions, top by confidence:

A	B	Type	Score
GNMT	GABRQ	psi-mi:“MI:0915”(physical association)	0.560
GABRQ	TXNDC12	psi-mi:“MI:0915”(physical association)	0.400
HLA-G	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CLEC2B	ADAM10	psi-mi:“MI:0914”(association)	0.350
GNMT	GABRQ	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): GABRQ (Affinity Capture-RNA), GABRQ (Two-hybrid), GABRQ (Proximity Label-MS), GABRQ (Affinity Capture-MS), GABRQ (Affinity Capture-MS)

ESM2 similar proteins: A8XF54, A8XNX8, G5ECJ0, G5ECT0, G5EDN0, G5EG88, O00591, O09028, O16926, O18276, O35119, O70174, O76554, P09478, P09482, P09483, P17644, P18845, P20781, P25162, P41849, P45963, P48167, P48168, P48181, P48182, P48994, P54245, P54246, Q09453, Q18812, Q19351, Q21005, Q21974, Q23022, Q27218, Q5EA06, Q5IS77, Q60S81, Q86LG1

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1240 predictions. Top by Δscore:

Variant	Effect	Δscore
X:152638347:AACTG:A	donor_gain	1.0000
X:152638348:ACTG:A	donor_gain	1.0000
X:152638349:CTG:C	donor_gain	1.0000
X:152638350:TG:T	donor_gain	1.0000
X:152638351:GG:G	donor_gain	1.0000
X:152638352:G:GC	donor_loss	1.0000
X:152638352:G:GG	donor_gain	1.0000
X:152638353:T:G	donor_loss	1.0000
X:152640377:GCAAA:G	acceptor_gain	1.0000
X:152645521:TTCTA:T	acceptor_loss	1.0000
X:152645522:TCTAG:T	acceptor_loss	1.0000
X:152645523:CTA:C	acceptor_loss	1.0000
X:152645524:TA:T	acceptor_loss	1.0000
X:152645525:A:AG	acceptor_gain	1.0000
X:152645525:A:T	acceptor_loss	1.0000
X:152645526:G:GG	acceptor_gain	1.0000
X:152645526:G:GT	acceptor_loss	1.0000
X:152645526:GGT:G	acceptor_gain	1.0000
X:152647166:CCGGT:C	donor_loss	1.0000
X:152647169:G:GG	donor_gain	1.0000
X:152647170:TGAGT:T	donor_loss	1.0000
X:152647171:GAG:G	donor_loss	1.0000
X:152649236:T:A	acceptor_gain	1.0000
X:152649246:T:TA	acceptor_gain	1.0000
X:152649246:TGCA:T	acceptor_loss	1.0000
X:152649247:GCA:G	acceptor_loss	1.0000
X:152649248:CA:C	acceptor_loss	1.0000
X:152649249:A:AG	acceptor_gain	1.0000
X:152649249:A:AT	acceptor_loss	1.0000
X:152649250:G:GA	acceptor_gain	1.0000

AlphaMissense

4182 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:152646981:T:A	W114R	0.997
X:152646981:T:C	W114R	0.997
X:152647056:T:A	W139R	0.997
X:152647056:T:C	W139R	0.997
X:152647058:G:C	W139C	0.997
X:152647058:G:T	W139C	0.997
X:152646983:G:C	W114C	0.996
X:152646983:G:T	W114C	0.996
X:152649330:A:C	S203R	0.996
X:152649332:C:A	S203R	0.996
X:152649332:C:G	S203R	0.996
X:152646987:G:C	D116H	0.995
X:152646997:T:C	L119S	0.995
X:152640452:G:C	R75T	0.994
X:152640453:A:C	R75S	0.994
X:152640453:A:T	R75S	0.994
X:152647147:G:T	G169V	0.994
X:152647135:T:C	L165P	0.992
X:152649319:T:C	L199P	0.992
X:152646994:G:C	R118P	0.991
X:152650529:T:A	W284R	0.991
X:152650529:T:C	W284R	0.991
X:152647063:C:A	P141H	0.990
X:152646988:A:C	D116A	0.989
X:152647147:G:A	G169E	0.989
X:152649291:T:C	F190L	0.989
X:152649293:C:A	F190L	0.989
X:152649293:C:G	F190L	0.989
X:152649312:T:A	C197S	0.989
X:152649313:G:C	C197S	0.989

dbSNP variants (sampled 300 via entrez): RS1000688831 (X:152641362 G>A), RS1001550154 (X:152659346 T>C), RS1001811277 (X:152641742 G>A,T), RS1002114175 (X:152650800 A>T), RS1002596098 (X:152655215 A>G), RS1002690888 (X:152638178 C>G), RS1002703004 (X:152646426 G>A,T), RS1003212061 (X:152637897 T>A), RS1003486807 (X:152643929 A>T), RS1003809159 (X:152636044 C>T), RS1004000716 (X:152642364 A>G), RS1004668185 (X:152657900 A>T), RS1004866180 (X:152640768 C>G,T), RS1004928452 (X:152640175 G>A,C,T), RS1004975621 (X:152658231 T>C)

Disease associations

OMIM: gene MIM:300349 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2093872 (PROTEIN COMPLEX GROUP), CHEMBL3885575 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 442,649 (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
CHEMBL268254	DELORAZEPAM	2	1,308
CHEMBL275638	FLAVONE	2	88,985
CHEMBL287631	PROGABIDE	2	3,853
CHEMBL454095	ABECARNIL	2	566
CHEMBL8260	BAICALEIN	2	8,592
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
rs3810651	Efficacy	3	venlafaxine	Major Depressive Disorder

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3810651	GABRQ	3	3.00	1	venlafaxine

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

ChEMBL bioactivities

475 potent at pChembl≥5 of 512 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
8.77	Ki	1.7	nM	CHEMBL154342
8.74	IC50	1.8	nM	CHEMBL444050
8.70	IC50	2	nM	MUSCIMOL
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
8.48	IC50	3.3	nM	CHEMBL75642
8.40	IC50	3.981	nM	CHEMBL301605
8.40	Ki	4	nM	CHEMBL330116
8.40	Ki	4	nM	CHEMBL3407528

PubChem BioAssay actives

409 with measured affinity, of 875 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
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
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
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
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
Diazepam	1934094: Inhibition of GABA-A receptor (unknown origin)	ic50	0.0042	uM
4-acetyl-13-(4-chlorophenyl)-5-thia-13,14-diazatricyclo[8.4.0.02,6]tetradeca-1(10),2(6),3-trien-12-one	40977: Binding affinity for GABA-A Benzodiazepine receptor	ki	0.0042	uM
1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole	242615: In vitro insecticidal activity as inhibition of [3H]EBOB binding to Gamma-aminobutyric acid GABA-A receptor of housefly neuronal membranes	ic50	0.0042	uM
2-amino-N-[4-chloro-2-(2-chlorobenzoyl)phenyl]acetamide	40974: In vitro displacement of [3H]-diazepam from GABA-A Benzodiazepine receptor	ic50	0.0048	uM
3-(7-fluoro-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	0.0050	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, affects expression, affects cotreatment	2
Valproic Acid	decreases methylation, increases expression	2
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Lead	affects expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Cyclosporine	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

186 unique, capped per target: 167 binding, 15 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

Clinical trials (associated diseases)

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