GABRB3

Summary

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

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

Source: NCBI Gene 2562 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 815 total — 45 pathogenic, 53 likely-pathogenic (top 4% of genes corpus-wide)
• Regional missense constraint (gnomAD): 2 of 6 regions constrained (≈41% of expected missense variation)
• GTEx eGene: eQTL in 33 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 58
• Drug target: yes — 1 curated mechanism-of-action drug, 2 via a complex or family; 32 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs acting on a complex or family including it: 1 — Zopiclone (GABA-A receptor; agonist GABA site)
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.44 (moderately constrained)
• MANE Select transcript: NM_000814

Identifiers

Gene identifiers

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

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 12 protein_coding_CDS_not_defined, 9 protein_coding, 6 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000311550

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 5, TSL 3: 1, TSL 5: 14

ENST00000311550, ENST00000299267, ENST00000400188, ENST00000541819, ENST00000545868, ENST00000554556, ENST00000554722, ENST00000555094, ENST00000555632, ENST00000556166, ENST00000556636, ENST00000557641, ENST00000557765, ENST00000621499, ENST00000635832, ENST00000635994, ENST00000636466, ENST00000636512, ENST00000636690, ENST00000637226, ENST00000637293, ENST00000637893, ENST00000638099, ENST00000638149, ENST00001069312, ENST00001114006, ENST00001114007, ENST00001129123

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

CCDS: CCDS10018, CCDS10019, CCDS53920, CCDS53921

Canonical transcript exons

ENST00000311550 — 9 exons

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

Expression profiles

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

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

Highest expression (Bgee): middle temporal gyrus, cortical plate, Brodmann (1909) area 23, entorhinal cortex, endothelial cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GABRB3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 33 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 33 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	7.4e-39	+0.75	15:26629248:T:C
Cells Cultured fibroblasts	eqtl	2.0e-35	+0.67	15:26626629:C:T
Esophagus Muscularis	eqtl	1.3e-34	+0.65	15:26629248:T:C
Adipose Subcutaneous	eqtl	3.3e-33	+0.66	15:26629248:T:C
Esophagus Mucosa	eqtl	3.7e-30	+0.73	15:26629248:T:C
Skin Sun Exposed Lower leg	eqtl	2.3e-29	+0.66	15:26629248:T:C
Breast Mammary Tissue	eqtl	1.5e-27	+0.75	15:26629248:T:C
Adipose Visceral Omentum	eqtl	1.6e-26	+0.67	15:26629248:T:C
Skin Not Sun Exposed Suprapubic	eqtl	9.6e-26	+0.70	15:26629248:T:C
Artery Aorta	eqtl	1.2e-23	+0.76	15:26629248:T:C
Lung	eqtl	2.6e-22	+0.58	15:26629248:T:C
Esophagus Gastroesophageal Junction	eqtl	3.0e-21	+0.62	15:26629248:T:C
Nerve Tibial	eqtl	4.0e-20	+0.40	15:26629248:T:C
Colon Transverse	eqtl	5.6e-19	+0.46	15:26629700:T:C
Colon Sigmoid	eqtl	2.6e-16	+0.49	15:26629248:T:C
Heart Left Ventricle	eqtl	2.6e-13	+0.51	15:26629248:T:C
Testis	eqtl	2.8e-11	-0.47	15:26629378:C:T
Artery Coronary	eqtl	6.4e-09	+0.59	15:26629248:T:C
Stomach	eqtl	2.3e-08	+0.32	15:26629248:T:C
Uterus	eqtl	3.8e-07	-0.67	15:26625455:C:T

FANTOM5 promoters

10 alternative TSS:

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

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	98.03	gold quality
cortical plate	UBERON:0005343	97.24	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.85	gold quality
entorhinal cortex	UBERON:0002728	96.51	gold quality
endothelial cell	CL:0000115	95.63	gold quality
parietal lobe	UBERON:0001872	95.17	gold quality
postcentral gyrus	UBERON:0002581	94.93	gold quality
superior frontal gyrus	UBERON:0002661	94.93	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.84	gold quality
islet of Langerhans	UBERON:0000006	93.35	gold quality
prefrontal cortex	UBERON:0000451	92.00	gold quality
occipital lobe	UBERON:0002021	91.99	gold quality
primary visual cortex	UBERON:0002436	91.65	gold quality
lateral globus pallidus	UBERON:0002476	91.00	gold quality
nucleus accumbens	UBERON:0001882	90.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.95	gold quality
frontal cortex	UBERON:0001870	90.87	gold quality
frontal lobe	UBERON:0016525	90.86	gold quality
cerebral cortex	UBERON:0000956	90.38	gold quality
ganglionic eminence	UBERON:0004023	90.27	gold quality
neocortex	UBERON:0001950	90.16	gold quality
right frontal lobe	UBERON:0002810	89.95	gold quality
temporal lobe	UBERON:0001871	89.84	gold quality
telencephalon	UBERON:0001893	89.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.33	gold quality
forebrain	UBERON:0001890	88.89	gold quality
Ammon’s horn	UBERON:0001954	88.55	gold quality
brain	UBERON:0000955	87.86	gold quality
caudate nucleus	UBERON:0001873	87.64	gold quality
cerebellar cortex	UBERON:0002129	87.56	gold quality
cerebellar hemisphere	UBERON:0002245	87.56	gold quality
central nervous system	UBERON:0001017	87.31	gold quality
substantia nigra pars compacta	UBERON:0001965	87.28	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.15	gold quality
cingulate cortex	UBERON:0003027	87.10	gold quality
pituitary gland	UBERON:0000007	87.02	gold quality
anterior cingulate cortex	UBERON:0009835	86.88	gold quality
dorsal root ganglion	UBERON:0000044	86.79	gold quality
cerebellum	UBERON:0002037	86.75	gold quality
superior vestibular nucleus	UBERON:0007227	86.72	gold quality
ventral tegmental area	UBERON:0002691	86.55	gold quality
putamen	UBERON:0001874	86.37	gold quality
substantia nigra pars reticulata	UBERON:0001966	86.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.66	gold quality
pons	UBERON:0000988	85.62	gold quality
amygdala	UBERON:0001876	85.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.42	gold quality
adenohypophysis	UBERON:0002196	85.28	gold quality
cerebellar vermis	UBERON:0004720	85.11	gold quality
gall bladder	UBERON:0002110	84.95	gold quality
buccal mucosa cell	CL:0002336	84.75	gold quality
frontal pole	UBERON:0002795	83.95	gold quality
globus pallidus	UBERON:0001875	83.82	gold quality
medial globus pallidus	UBERON:0002477	83.73	gold quality
corpus callosum	UBERON:0002336	82.84	gold quality
hypothalamus	UBERON:0001898	82.45	gold quality
trigeminal ganglion	UBERON:0001675	81.78	gold quality
Brodmann (1909) area 46	UBERON:0006483	81.09	gold quality
right atrium auricular region	UBERON:0006631	80.03	gold quality
ventricular zone	UBERON:0003053	79.69	gold quality
dorsal plus ventral thalamus	UBERON:0001897	78.96	gold quality
adult organism	UBERON:0007023	78.80	gold quality
medulla oblongata	UBERON:0001896	78.79	gold quality
cardiac atrium	UBERON:0002081	78.68	gold quality
pancreas	UBERON:0001264	78.14	gold quality
sural nerve	UBERON:0015488	75.66	gold quality
midbrain	UBERON:0001891	75.63	gold quality
stromal cell of endometrium	CL:0002255	75.35	gold quality
substantia nigra	UBERON:0002038	74.91	gold quality
embryo	UBERON:0000922	74.28	gold quality
caput epididymis	UBERON:0004358	73.90	gold quality
bronchial epithelial cell	CL:0002328	73.15	gold quality
orbitofrontal cortex	UBERON:0004167	73.14	gold quality
adrenal tissue	UBERON:0018303	73.01	gold quality
pancreatic ductal cell	CL:0002079	72.88	silver quality
left lobe of thyroid gland	UBERON:0001120	72.87	gold quality
thyroid gland	UBERON:0002046	72.77	gold quality
stomach	UBERON:0000945	72.00	gold quality
subthalamic nucleus	UBERON:0001906	71.93	gold quality
body of pancreas	UBERON:0001150	71.73	gold quality
body of stomach	UBERON:0001161	71.67	gold quality
pigmented layer of retina	UBERON:0001782	71.29	gold quality
retina	UBERON:0000966	71.28	gold quality
right lobe of thyroid gland	UBERON:0001119	70.90	gold quality
type B pancreatic cell	CL:0000169	70.53	gold quality
spinal cord	UBERON:0002240	70.32	gold quality
paraflocculus	UBERON:0005351	70.27	gold quality
inferior vagus X ganglion	UBERON:0005363	70.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	70.00	gold quality
testis	UBERON:0000473	69.90	gold quality
renal medulla	UBERON:0000362	69.68	gold quality
right testis	UBERON:0004534	69.65	gold quality
epithelium of bronchus	UBERON:0002031	68.93	gold quality
adult mammalian kidney	UBERON:0000082	68.59	gold quality
left testis	UBERON:0004533	68.50	gold quality
bronchus	UBERON:0002185	68.22	gold quality
middle frontal gyrus	UBERON:0002702	68.17	gold quality
metanephros cortex	UBERON:0010533	67.65	gold quality
heart	UBERON:0000948	67.38	gold quality
fundus of stomach	UBERON:0001160	67.37	gold quality

Single-cell (SCXA)

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

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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 73 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Caudate putamen	tissue	115.5
Hippocampal formation	tissue	103.3
Frontal cortex	tissue	96.6
Prefrontal cortex	tissue	94.5
Cerebral cortex	tissue	94.5
Motor cortex	tissue	87.2
Somatosensory cortex	tissue	86.9
Retrosplenial and cingulate cortex	tissue	85.1
Entorhinal cortex	tissue	84.8
Occipital cortex	tissue	82.6
Temporal cortex	tissue	80.0
Basal ganglia	tissue	78.8
Insular cortex	tissue	74.6
Retrosplenial cortex	tissue	72.6
Putamen	tissue	70.6
Ventral forebrain	tissue	69.7
Postcentral gyrus	tissue	67.0
Septum	tissue	66.8
Olfactory bulb	tissue	64.0
Amygdala	tissue	62.2
Hippocampus	tissue	48.4
Thalamus	tissue	45.6
Nucleus accumbens	tissue	45.0
Hypothalamus	tissue	41.9
Cerebellum	tissue	37.3
Midbrain	tissue	36.5
Pons	tissue	36.4
Superior colliculi	tissue	35.0
Retina	tissue	28.0
Periaqueductal gray	tissue	21.7
Locus coeruleus	tissue	19.9
Medulla oblongata	tissue	18.8
Spinal cord	tissue	18.2
Substantia nigra	tissue	17.4
Gallbladder	tissue	12.8
Corpus callosum	tissue	8.4
Thyroid gland	tissue	8.0
Kidney	tissue	6.7
Stomach 1	tissue	5.3
Adrenal gland	tissue	5.1
Heart muscle	tissue	5.0
Pituitary gland	tissue	4.5
Prostate	tissue	4.5
Testis	tissue	3.6
Pancreas	tissue	3.1
Choroid plexus	tissue	2.4
Cervix	tissue	2.1
Parathyroid gland	tissue	1.9
Fallopian tube	tissue	1.9
Ovary	tissue	1.7
Endometrium 1	tissue	1.6
Thymus	tissue	1.4
Smooth muscle	tissue	1.2
Esophagus	tissue	1.1
Colon	tissue	1.1
Seminal vesicle	tissue	1.0
Urinary bladder	tissue	1.0
Rectum	tissue	0.9
Epididymis	tissue	0.9
Lung	tissue	0.8

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Dorsal hippocampus (103.3), Subiculum (91.7), Ventral hippocampus (91.7), Olfactory area (80.9), Perirhinal gyrus (77.0).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting GABRB3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 183 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.999, LOEUF 0.439, missense Z 4.46 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000311550 splits into 6 regions with different missense tolerance; 2 are missense-constrained (≈41% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
15:26,547,796–26,560,993	115 / 166.9	0.69	no
15:26,560,994–26,580,338	32 / 147.8	0.22	yes (p 1.7e-21)
15:26,580,339–26,580,412	23 / 34.2	0.67	no
15:26,580,413–26,621,422	16 / 102.6	0.16	yes (p 1.2e-17)
15:26,621,423–26,772,449	31 / 71.2	0.44	no
15:26,772,450–26,772,962	90 / 86.4	1.04	no
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

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

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabrb1	ENSDARG00000076127
mus_musculus	Gabrb3	ENSMUSG00000033676
rattus_norvegicus	Gabrb3	ENSRNOG00000060599

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090), GABRA5 (ENSG00000186297), ZACN (ENSG00000186919), GABRD (ENSG00000187730), CHRNG (ENSG00000196811), GABRQ (ENSG00000268089)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95621) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 91 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal CNS synaptic transmission	4
circling	3
hyperactivity	3
cleft palate	2
abnormal maternal nurturing	2
reduced male fertility	2
seizures	2
abnormal righting response	2
absence seizures	2
abnormal behavior	2
abnormal action potential	2
impaired behavioral response to xenobiotic	2
abnormal cochlea morphology	1
myoclonus	1
tremors	1
obese	1
decreased body size	1
increased anxiety-related response	1
decreased male mating frequency	1
hyperresponsive	1
impaired coordination	1
increased stereotypic behavior	1
abnormal nest building behavior	1
limb grasping	1
impaired swimming	1

+66 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca mulatta	D1LYT2	100.0%	Diamond
Drosophila melanogaster	P25123	99.8%	Diamond
Bos taurus	P57695	99.8%	Diamond
Macaca fascicularis	Q4R534	99.8%	Diamond
Pongo abelii	Q5RCC5	99.8%	Diamond
Drosophila simulans	Q9BLY8	99.8%	Diamond
Gallus gallus	P19150	96.9%	Diamond
Musca domestica	Q75NA5	84.3%	Diamond
Haemonchus contortus	P91730	81.4%	Diamond
Caenorhabditis elegans	Q17328	81.4%	Diamond
Lymnaea stagnalis	P26714	58.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GABRA5	protein-coding	2558
LINC02248	ncRNA	107984780
LINC00929	ncRNA	503519
TRE-TTC2-2	tRNA	100189063
GABRG3	protein-coding	2567

Protein

Protein identifiers

Gamma-aminobutyric acid receptor subunit beta-3 — P28472 (reviewed: P28472)

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

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

UniProt curated annotations — full annotation on UniProt →

Function. Beta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain. GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s). GABAARs containing beta-3/GABRB3 subunit are found at both synaptic and extrasynaptic sites. When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission. GABAARs containing alpha-1 and beta-3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation. Extrasynaptic beta-3 receptors contribute to the tonic GABAergic inhibition. GABAARs containing alpha-1, beta-3 and epsilon subunits may also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings. Beta-containing GABAARs can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness. Plays an important role in somatosensation and in the production of antinociception.

Subunit / interactions. Heteropentamer, formed by a combination of alpha (GABRA1-6), beta (GABRB1-3), gamma (GABRG1-3), delta (GABRD), epsilon (GABRE), rho (GABRR1-3), pi (GABRP) and theta (GABRQ) chains, each subunit exhibiting distinct physiological and pharmacological properties. Can form functional homopentamers (in vitro). Interacts with UBQLN1. May interact with KIF21B. Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3. Interacts with LHFPL4. Interacts with GIT1; this interaction is required for synaptic GABRB3 surface stability and inhibitory synapse strength.

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

Disease relevance. Epilepsy, childhood absence 5 (ECA5) [MIM:612269] A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Absence seizures may either remit or persist into adulthood. Disease susceptibility is associated with variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 43 (DEE43) [MIM:617113] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE43 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Potentiated by histamine.

Domain organisation. GABAARs subunits share a common topological structure: a peptide sequence made up of a long extracellular N-terminal, four transmembrane domains, intracellular or cytoplasmic domain located between the third and the fourth transmembrane domains.

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

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

Isoforms (4)

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

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

Domains & families (InterPro)

ID	Name	Type
IPR002289	GABAAb_rcpt	Family
IPR006028	GABAA/Glycine_rcpt	Family
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR018000	Neurotransmitter_ion_chnl_CS	Conserved_site
IPR036719	Neuro-gated_channel_TM_sf	Homologous_superfamily
IPR036734	Neur_chan_lig-bd_sf	Homologous_superfamily
IPR038050	Neuro_actylchol_rec	Homologous_superfamily

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea)

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

UniProt features (76 total): sequence variant 17, strand 13, helix 12, binding site 10, topological domain 5, transmembrane region 4, turn 4, glycosylation site 3, splice variant 3, sequence conflict 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

showing 30 of 109 structures by resolution:

PDB	Title	Method	Resolution (Å)
7A5V	CryoEM structure of a human gamma-aminobutyric acid receptor, the GABA(A)R-beta3 …	ELECTRON MICROSCOPY	1.7
9RGD	CryoEM structure of human alpha1beta3gamma2L GABA(A)R in CL47a	ELECTRON MICROSCOPY	2
9EQG	CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with GABA …	ELECTRON MICROSCOPY	2.4
6QFA	CryoEM structure of a beta3K279T GABA(A)R homomer in complex with histamine and megabody …	ELECTRON MICROSCOPY	2.49
7QN5	Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex …	ELECTRON MICROSCOPY	2.5
9FAS	CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with …	ELECTRON MICROSCOPY	2.5
9FEU	Cryo-EM structure of the beta3 homomeric GABA(A) receptor in complex with HSM in the …	ELECTRON MICROSCOPY	2.5
9FFU	Cryo-EM structure of the alpha1beta3 GABA(A) receptor in complex with GABA and Mb25 in …	ELECTRON MICROSCOPY	2.5
9G2E	Cryo-EM structure of the beta3 homomeric GABA(A) receptor in the long-lived desensitised …	ELECTRON MICROSCOPY	2.5
9QJS	GABA-A receptor a2b3 (1:4) + a2NB16(silent) + b3Mb125 + GABA	ELECTRON MICROSCOPY	2.52
8PET	Cryo-EM structure of the full-length human alpha1beta3 GABA(A) receptor (babba …	ELECTRON MICROSCOPY	2.6
9FAJ	CryoEM structure of human full-length alpha1beta3gamma2 GABA(A) receptor in complex with …	ELECTRON MICROSCOPY	2.6
9FAK	CryoEM structure of human full-length alpha1beta3gamma2 GABA(A) receptor in complex with …	ELECTRON MICROSCOPY	2.6
9FEX	Cryo-EM structure of the beta3 homomeric GABA(A) receptor in complex with HSM in the …	ELECTRON MICROSCOPY	2.6
9FGG	Cryo-EM structure of the full-length alpha1beta3gamma2 GABA(A) receptor in Saposin A …	ELECTRON MICROSCOPY	2.6
9SL1	GABA-A a4b3d receptor in complex with GABA, Nb24 and Mb30	ELECTRON MICROSCOPY	2.68
7QNE	Cryo-EM structure of human full-length synaptic alpha1beta3gamma2 GABA(A)R in complex …	ELECTRON MICROSCOPY	2.7
9FG7	Cryo-EM structure of the full-length alpha1beta3gamma2 GABA(A) receptor in complex with …	ELECTRON MICROSCOPY	2.7
9FG9	Cryo-EM structure of the full-length alpha1beta3gamma2 GABA(A) receptor in complex with …	ELECTRON MICROSCOPY	2.7
9G2D	Cryo-EM structure of the beta3 homomeric GABA(A) receptor in the long-lived resting state …	ELECTRON MICROSCOPY	2.7
9QJX	GABA-A receptor a2b3g2 + a2NB00(PAM) + GABA	ELECTRON MICROSCOPY	2.7
9QJY	GABA-A receptor a2b3g2 + a2NB04(silent) + GABA	ELECTRON MICROSCOPY	2.78
7PBZ	a1b3 GABA-A receptor + GABA + Zn2+	ELECTRON MICROSCOPY	2.79
9FAP	CryoEM structure of human full-length alpha1beta3gamma2 GABA(A)R in complex with GARLH4 …	ELECTRON MICROSCOPY	2.8
9FF2	Cryo-EM structure of the beta3 homomeric GABA(A) receptor in complex with HSM in the …	ELECTRON MICROSCOPY	2.8
9FFL	Cryo-EM structure of the alpha1beta3 GABA(A) receptor in complex with GABA and Mb25 in …	ELECTRON MICROSCOPY	2.8
9FFV	Cryo-EM structure of the alpha1beta3gamma2 GABA(A) receptor in complex with Nb38 in the …	ELECTRON MICROSCOPY	2.8
7QN6	Cryo-EM structure of human full-length beta3delta GABA(A)R in complex with nanobody Nb25	ELECTRON MICROSCOPY	2.9
7QN9	Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex …	ELECTRON MICROSCOPY	2.9
7QNC	Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex …	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab)

57 antibodies co-crystallized with this protein: 5O8F, 5OJM, 6A96, 6HUG, 6HUJ, 6HUK, 6HUO, 6HUP, 6I53, 6QFA, 7A5V, 7PBD, 7PBZ, 7PC0, 7QN5, 7QN6, 7QN7, 7QN8, 7QN9, 7QNA, 7QNB, 7QNC, 7QND, 7QNE, 8PET (+32 more)

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted membrane proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Epilepsy

Protein evidence: Evidence at protein level

Functional residue map

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

Ligand- & substrate-binding residues (10)

Position	Role
120–122	benzamidine
122	4-aminobutanoate
122	histamine
180–182	benzamidine
180	4-aminobutanoate
181–182	histamine
182	4-aminobutanoate
225	benzamidine
227	4-aminobutanoate
227	histamine

Disulfide bonds (1)

Type	Positions
Disulfide bond	161–175

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	33, 105, 174

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-977443	GABA receptor activation	electronic
R-HSA-112316	Neuronal System	—
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission	—
R-HSA-162582	Signal Transduction	—
R-HSA-1236394	Signaling by ERBB4	electronic
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-112315	Transmission across Chemical Synapses	—

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

GO Biological Process (19): signal transduction (GO:0007165), gamma-aminobutyric acid signaling pathway (GO:0007214), negative regulation of synaptic transmission, GABAergic (GO:0032229), synaptic transmission, GABAergic (GO:0051932), roof of mouth development (GO:0060021), inhibitory postsynaptic potential (GO:0060080), inner ear receptor cell development (GO:0060119), innervation (GO:0060384), cellular response to histamine (GO:0071420), cochlea development (GO:0090102), extrasynaptic signaling via GABA (GO:0160001), 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), genomic imprinting (GO:0071514)

GO Molecular Function (10): GABA-A receptor activity (GO:0004890), GABA-gated chloride ion channel activity (GO:0022851), identical protein binding (GO:0042802), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), transmembrane signaling receptor activity (GO:0004888), signaling receptor binding (GO:0005102), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), chloride channel activity (GO:0005254), signaling receptor activity (GO:0038023)

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

Reactome top-level categories

5 top-level categories:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	1
Neurotransmitter receptors and postsynaptic signal transmission	1
Transmission across Chemical Synapses	1
Neuronal System	1
Signal Transduction	1

GO top-level categories

showing 60 of 63 GO namespaces:

Category	Terms
GABA receptor activity	2
animal gross anatomical part developmental process	2
regulation of postsynaptic membrane potential	2
transmitter-gated monoatomic ion channel activity	2
protein binding	2
cellular anatomical structure	2
postsynapse	2
synaptic membrane	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell-cell signaling	1
regulation of synaptic transmission, GABAergic	1
negative regulation of synaptic transmission	1
synaptic transmission, GABAergic	1
chemical synaptic transmission	1
chemical synaptic transmission, postsynaptic	1
neuron development	1
inner ear receptor cell differentiation	1
nerve development	1
multicellular organismal process	1
response to histamine	1
cellular response to nitrogen compound	1
inner ear development	1
gamma-aminobutyric acid signaling pathway	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
germ cell development	1
epigenetic programming of gene expression	1
chloride channel activity	1
ligand-gated monoatomic anion channel activity	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
vesicle membrane	1
cytoplasmic vesicle	1
monoatomic ion channel complex	1
dendrite	1
neuron spine	1
synapse	1
postsynaptic membrane	1
postsynaptic specialization	1
GABA receptor complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 41 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to histamine	BP	direct assay
chloride transmembrane transport	BP	direct assay
gamma-aminobutyric acid signaling pathway	BP	direct assay
inhibitory synapse assembly	BP	direct assay
synaptic transmission, GABAergic	BP	direct assay
GABA-A receptor complex	CC	direct assay
dendritic spine	CC	direct assay
plasma membrane	CC	direct assay
postsynaptic membrane	CC	direct assay
GABA-A receptor activity	MF	direct assay
GABA-gated chloride ion channel activity	MF	direct assay
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,644 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRB3	UBE3A	P78355	860
GABRB3	SNRPN	P14648	839
GABRB3	ATP10A	O60312	815
GABRB3	MECP2	P51608	771
GABRB3	SHANK3	Q9BYB0	737
GABRB3	MKRN3	Q13064	729
GABRB3	NDN	Q99608	702
GABRB3	GABRA5	P31644	690
GABRB3	CDKL5	O76039	688
GABRB3	GAD1	Q99259	672
GABRB3	CLCN2	P51788	662
GABRB3	CACNA1H	O95180	662
GABRB3	GABRG3	Q99928	635
GABRB3	OCA2	Q04671	628
GABRB3	GAD2	Q05329	628

IntAct

Human interaction partners of GABRB3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
MEOX2	physical association	0.370	1
GABRA5	direct interaction	0.360	1
GABRB2	association	0.350	1
GABRD	physical association	0.320	3
GABRG2	physical association	0.320	1

BioGRID (23 interactions; top human partners by supporting records): MCOLN3 (Affinity Capture-MS; 3 records), AKAP5 (Reconstituted Complex; 2 records), GABRA6 (Affinity Capture-MS; 2 records), GABRB2 (Affinity Capture-MS; 2 records), UBQLN1 (Affinity Capture-Western; 2 records), ASIC4 (Affinity Capture-MS), CHRNA4 (Affinity Capture-MS), CHRNB4 (Affinity Capture-MS), DDX58 (Affinity Capture-RNA), GLRA3 (Affinity Capture-MS), MEOX2 (Two-hybrid), PRKACA (Reconstituted Complex), PRKCA (Reconstituted Complex), PRNP (Affinity Capture-MS), RAB5C (Affinity Capture-MS)

SIGNOR signaling

2 signaling interactions:

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

Ligand–receptor pairs (CellPhoneDB) (11)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

11 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
GABRA6;GABRB3;GABRG2		Signaling by GABA
GABRA2;GABRB3;GABRG2		Signaling by GABA
GABRA3;GABRB3;GABRE		Signaling by GABA
GABRA3;GABRB3;GABRG2		Signaling by GABA
GABRA4;GABRB3;GABRD		Signaling by GABA
GABRA1;GABRB3;GABRG2		Signaling by GABA
GABRA3;GABRB3;GABRQ		Signaling by GABA
GABRA6;GABRB3;GABRD		Signaling by GABA
GABRA4;GABRB3;GABRG2		Signaling by GABA
GABRA1;GABRB3		Signaling by GABA
GABRA5;GABRB3;GABRG2		Signaling by GABA

Disease & clinical

Genetic variants

Variant evidence for GABRB3: 815 ClinVar records (98 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 10 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	45
Likely pathogenic	53
Uncertain significance	324
Likely benign	273
Benign	51

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 98 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1723205	NM_000814.6(GABRB3):c.580C>T (p.Arg194Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
653036	NM_000814.6(GABRB3):c.331C>T (p.Arg111Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
942245	NM_000814.6(GABRB3):c.405del (p.Thr135_Val136insTer)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
409956	NM_000814.6(GABRB3):c.504C>A (p.Tyr168Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
429597	NM_000814.6(GABRB3):c.554C>T (p.Thr185Ile)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
372868	NM_000814.6(GABRB3):c.838A>T (p.Ile280Phe)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
837360	NM_000814.6(GABRB3):c.902C>T (p.Pro301Leu)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3754031	NM_000814.6(GABRB3):c.229G>C (p.Glu77Gln)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
4261134	NM_000814.6(GABRB3):c.1080+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
975243	NM_000814.6(GABRB3):c.901C>T (p.Pro301Ser)	Pathogenic	criteria provided, single submitter	2
1453717	NM_000814.6(GABRB3):c.860C>T (p.Thr287Ile)	Pathogenic	criteria provided, single submitter	2
3600364	NM_000814.6(GABRB3):c.238A>G (p.Met80Val)	Pathogenic	criteria provided, single submitter	2
582255	NM_000814.6(GABRB3):c.895A>C (p.Lys299Gln)	Pathogenic	criteria provided, single submitter	1
943697	NM_000814.6(GABRB3):c.1054del (p.Asp352fs)	Pathogenic	criteria provided, single submitter	1
969517	NM_000814.6(GABRB3):c.172+1del	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore GABRB3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 40 predictions of 1,658):

Position(s)	Effect	Δscore	Sites
15:26561177–26561178	acceptor_loss	1.0000	5
15:26567579–26567580	donor_loss	1.0000	5
15:26580317–26580318	donor_loss	1.0000	5
15:26580457–26580458	acceptor_loss	1.0000	5
15:26583333	donor_gain	1.0000
15:26772400–26772401	donor_loss	1.0000	4
15:26772470–26772471	acceptor_loss	1.0000	5
15:26772679–26772680	donor_loss	1.0000	4
15:26772773–26772774	acceptor_loss	1.0000	5
15:26561177	acceptor_loss	0.9900

AlphaMissense

1,718 missense substitutions predicted likely pathogenic (of 3,106 scored), across 331 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M80	9	0.973	1.000
M163	9	0.970	0.999
M286	9	0.946	0.999
M140	9	0.940	0.999
D94	8	0.999	1.000
D120	8	0.999	1.000
N138	8	0.999	1.000
D171	8	0.999	1.000
D307	8	0.999	1.000
D449	8	0.999	1.000
D109	8	0.998	1.000
H132	8	0.998	1.000
F265	8	0.998	1.000
D49	8	0.997	0.999
F318	8	0.996	1.000
D126	8	0.993	0.999
D188	8	0.993	0.999
D81	8	0.991	0.999
S181	8	0.988	1.000
F456	8	0.988	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.47e-09
Glioblastoma Multiforme (validation)	favorable	0.000255
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000818

Disease associations

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

GenCC curated gene-disease

5 curated gene-disease records:

Disease	Classification	Inheritance	Records
developmental and epileptic encephalopathy, 43	Definitive	Autosomal dominant	3
genetic developmental and epileptic encephalopathy	Definitive	Autosomal dominant
epilepsy, childhood absence, susceptibility to, 5	Definitive	Autosomal dominant	2
Lennox-Gastaut syndrome	Supportive	Autosomal dominant
childhood absence epilepsy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
DDG2P	green
Early onset or syndromic epilepsy	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (8): epilepsy, childhood absence, susceptibility to, 5 (MONDO:0012843), developmental and epileptic encephalopathy, 43 (MONDO:0014921), epilepsy, childhood absence, susceptibility to, 1 (MONDO:0020759), epilepsy (MONDO:0005027), intellectual disability (MONDO:0001071), genetic developmental and epileptic encephalopathy (MONDO:0100062), Lennox-Gastaut syndrome (MONDO:0016532), childhood absence epilepsy (MONDO:0010826)

Orphanet (2): Childhood absence epilepsy (Orphanet:64280), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

58 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000737	Irritability
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000752	Hyperactivity
HP:0000980	Pallor
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001328	Specific learning disability
HP:0001336	Myoclonus
HP:0002069	Bilateral tonic-clonic seizure
HP:0002121	Generalized non-motor (absence) seizure
HP:0002123	Generalized myoclonic seizure
HP:0002321	Vertigo
HP:0002353	EEG abnormality
HP:0002360	Sleep disturbance
HP:0002363	Abnormal brainstem morphology
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002376	Developmental regression
HP:0002521	Hypsarrhythmia
HP:0002527	Falls
HP:0002883	Hyperventilation
HP:0003593	Infantile onset
HP:0003829	Typified by incomplete penetrance
HP:0006961	Jerky head movements
HP:0007018	Attention deficit hyperactivity disorder
HP:0007270	Atypical absence seizure
HP:0007359	Focal-onset seizure
HP:0007738	Uncontrolled eye movements
HP:0010522	Dyslexia
HP:0010794	Impaired visuospatial constructive cognition
HP:0010818	Generalized tonic seizure
HP:0010819	Atonic seizure
HP:0010848	EEG with spike-wave complexes (2.5-3.5 Hz)
HP:0011147	Typical absence seizure
HP:0011150	Myoclonic absence seizure
HP:0011195	EEG with focal sharp slow waves
HP:0012075	Personality disorder
HP:0012433	Abnormal social behavior
HP:0012469	Infantile spasms
HP:0012758	Neurodevelopmental delay
HP:0030218	Punding
HP:0031469	Low self-esteem
HP:0032794	Myoclonic seizure
HP:0045084	Limb myoclonus
HP:0100660	Dyskinesia
HP:0100710	Impulsivity
HP:0200134	Epileptic encephalopathy

GWAS associations

10 associations:

Study	Trait	p-value
GCST010002_214	Refractive error	4e-11
GCST004904_93	Body mass index	3e-8
GCST000785_3	Longevity	1e-6
GCST000477_25	Cognitive performance	2e-6
GCST008170_3	Thyroglobulin plasma levels	2e-6
GCST002408_14	Response to methotrexate in juvenile idiopathic arthritis	3e-6
GCST011050_4	Postprandial triglyceride response	3e-6
GCST010396_211	Gut microbiota (bacterial taxa, hurdle binary method)	4e-6
GCST008181_11	Spontaneous preterm birth without premature rupture of membranes	5e-6
GCST009196_2	Pericalcarine cortex volume	7e-6

EFO canonical traits (from GWAS)

6 canonical traits:

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

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065768	Lennox Gastaut Syndrome	C10.228.140.490.493.750; C16.320.495

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

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

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the GABRB3 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
ETAZOLATE	Small molecule	2

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes GABRB3 — the drug acts on the assembly or class, not necessarily on this subunit alone.

2 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
ZOPICLONE	GABA-A receptor; agonist GABA site	9	4
GABOXADOL	Gamma-aminobutyric acid receptor subunit alpha-4/beta3/delta	3	3

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 440,023 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

32 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3183409	APALUTAMIDE	4	4,347
CHEMBL207538	BREXANOLONE	4	1,647
CHEMBL451	CHLORDIAZEPOXIDE	4	36,835
CHEMBL452	CLONAZEPAM	4	33,611
CHEMBL12	DIAZEPAM	4	92,923
CHEMBL1082407	ENZALUTAMIDE	4	10,210
CHEMBL407	FLUMAZENIL	4	7,208
CHEMBL13280	FLUNITRAZEPAM	4	11,627
CHEMBL1568698	GANAXOLONE	4	1,695
CHEMBL15891	LINDANE	4	83,776
CHEMBL1544	LIOTHYRONINE	4	23,991
CHEMBL448	PENTOBARBITAL	4	50,134
CHEMBL526	PROPOFOL	4	29,086
CHEMBL646	TRIAZOLAM	4	21,762
CHEMBL1521	ZALEPLON	4	10,023
CHEMBL911	ZOLPIDEM	4	17,964
CHEMBL4105630	ZURANOLONE	4	300
CHEMBL454095	ABECARNIL	2	566
CHEMBL190279	ALFAXALONE	2	2,238
CHEMBL1783282	AZD7325	2	80
CHEMBL8260	BAICALEIN	2
CHEMBL3681419	BASMISANIL	2
CHEMBL366947	BRETAZENIL	2
CHEMBL3647536	DARIGABAT	2
CHEMBL268254	DELORAZEPAM	2
CHEMBL275638	FLAVONE	2
CHEMBL1397886	LORECLEZOLE	2
CHEMBL200177	MK-0777	2
CHEMBL287631	PROGABIDE	2
CHEMBL1783256	AZD6280	1
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1
CHEMBL273481	MUSCIMOL	1

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

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

PharmGKB variants

1 variants:

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

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs4906902	opioids	Toxicity	Genotype AA are associated with increased risk of Opioid-Related Disorders due to opioids in women as compared to genotypes AG + GG.	PMID:33589790

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

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

Ligand	Action	Affinity	Parameter
etazolate	Binding	5.46	pIC50

Binding affinities (BindingDB)

1759 measured of 1883 human assays (1887 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(4-Ethynyl-phenyl)-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.03 nM
8-Ethynyl-2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.06 nM
2-Phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one (CGS 8216)	KI	0.08 nM
8-Bromo-2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.08 nM
2’-fluoro-5’-(7-methyl-8-oxo-7,8-dihydroimidazo[1,2-a]pyrazin-3-yl)-1,1’-biphenyl-2-carbonitrile	KI	0.1 nM
7-(2-fluorophenyl)-2-((2-methyl-2H-1,2,4-triazol-3-yl)methoxy)-3-(thiophen-2-yl)pyrazolo[1,5-d][1,2,4]triazine	KI	0.1 nM
7-(2-fluorophenyl)-2-((2-methyl-2H-1,2,4-triazol-3-yl)methoxy)-3-(thiophen-3-yl)pyrazolo[1,5-d][1,2,4]triazine	KI	0.1 nM
PW-007A	KI	0.1 nM
7-(2-fluorophenyl)-3-(furan-2-yl)-2-((2-methyl-2H-1,2,4-triazol-3-yl)methoxy)pyrazolo[1,5-d][1,2,4]triazine	KI	0.11 nM
CHEMBL4476044	KI	0.12 nM
8-Hydroxy-5-methyl-6-oxo-5,6-dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid tert-butyl ester	KI	0.14 nM
4-(2-fluoro-5-(7-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyrimidin-3-yl)phenyl)nicotinonitrile	KI	0.14 nM
7-(2-fluorophenyl)-2-((2-methyl-2H-1,2,4-triazol-3-yl)methoxy)-3-(pyridin-4-yl)pyrazolo[1,5-d][1,2,4]triazine	KI	0.14 nM
3-Phenyl-6-(pyridazin-3-ylmethoxy)-[1,2,4]triazolo[3,4-a]phthalazine	KI	0.15 nM
5’-(7-ethyl-8-oxo-7,8-dihydroimidazo[1,2-a]pyrazin-3-yl)-2’,4-difluoro-1,1’-biphenyl-2-carbonitrile	KI	0.15 nM
8-Chloro-2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.17 nM
2-(4-Chloro-phenyl)-8-pyridin-4-ylmethyl-2,5,5a,6,7,8,9,9a-octahydro-pyrazolo[4,3-c][1,6]naphthyridin-3-one	KI	0.18 nM
2’,6-difluoro-5’-(7-methyl-8-oxo-7,8-dihydroimidazo[1,2-a]pyrazin-3-yl)-1,1’-biphenyl-2-carbonitrile	KI	0.19 nM
6-[[3-(5-chloro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-(oxan-4-yl)pyridine-3-carboxamide	KI	0.2 nM	US-20240279218: ISOXAZOLYL ETHER DERIVATIVES AS GABA A ALPHA5 PAM
11-(4-Chloro-phenyl)-9-(4-methyl-thiazol-2-yl)-6,7-dihydro-5H-2,7a-diaza-dibenzo[a,c]cyclohepten-8-one	KI	0.2 nM
2’-Fluoro-5’-[8-fluoro-7-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridin-3-yl]-biphenyl-2-carbonitrile	KI	0.2 nM
3-(2,5-difluorophenyl)-7-(2-fluorophenyl)-2-((2-methyl-2H-1,2,4-triazol-3-yl)methoxy)pyrazolo[1,5-d][1,2,4]triazine	KI	0.2 nM
ethyl 3-fluoro-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepine-10-carboxylate	KI	0.2 nM
3-(3-fluoro-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepin-10-yl)-5-methyl-1,2,4-oxadiazole	KI	0.2 nM
CHEMBL566181	KI	0.2 nM
CHEMBL567243	KI	0.2 nM
CHEMBL571466	KI	0.2 nM
CHEMBL566189	KI	0.2 nM
2-(4-Bromo-phenyl)-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.21 nM
3’-(7-trifluoromethyl-imidazo[1,2-a]pyrimidin-3-yl)-biphenyl-2-carbonitrile	KI	0.21 nM
CHEMBL4303594	KI	0.23 nM
7-cyclobutyl-6-(2-methyl-2H-1,2,4-trizol-3-ylmethoxy)-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine	KI	0.25 nM
5,2-difluoro-5-(7-trifluoromethylimidazo[1,2-a]pyrimidin-3-yl)biphenyl-2-carbonitrile	KI	0.26 nM
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
7-(2-fluorophenyl)-3-(3-fluorophenyl)-2-((2-methyl-2H-1,2,4-triazol-3-yl)methoxy)pyrazolo[1,5-d][1,2,4]triazine	KI	0.28 nM
8-Methoxy-5-methyl-6-oxo-5,6-dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid tert-butyl ester	KI	0.29 nM
2-(4-Fluoro-phenyl)-2,5,6,7,8,9-hexahydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.29 nM
7-tert-butyl-6-((2-ethyl-2H-1,2,4-triazol-3-yl)methoxy)-3-(2-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine	KI	0.3 nM
3-(2,6-difluorophenyl)-5-[4-fluoro-3-(3-fluoropyridin-2-yl)-phenyl]pyridazine	KI	0.3 nM
10-chloro-3-fluoro-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepine	KI	0.3 nM
10-chloro-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepine	KI	0.3 nM
CHEMBL565560	KI	0.3 nM
CHEMBL1783282	KI	0.309 nM
2-(4-Methoxy-phenyl)-2,5,6,7,8,9-hexahydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.31 nM
2-(3-(4-fluoro-3-(pyridin-4-yl)phenyl)imidazo[1,2-a]pyrimidin-7-yl)propan-2-ol	KI	0.31 nM
7-(trifluoromethyl)-3-(6-(trifluoromethyl)pyridin-2-yl)imidazo[1,2-a]pyrimidine	KI	0.31 nM
3-(6-bromopyridin-2-yl)-7-(trifluoromethyl)imidazo[1,2-a]pyrimidine	KI	0.31 nM
8-Chloro-2-(4-methoxy-phenyl)-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.32 nM
7-tert-butyl-6-(2-methyl-2H-1,2,4-trizol-3-ylmethoxy)-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine	KI	0.36 nM
2-(6-(7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl)pyridin-2-yl)benzonitrile	KI	0.36 nM

ChEMBL bioactivities

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

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

PubChem BioAssay actives

3352 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-(4-ethynylphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	73089: Binding affinity to human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-2-beta-3-gamma-2	ki	<0.0001	uM
8-ethynyl-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73244: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-3-beta-3-gamma-2	ki	<0.0001	uM
8-methoxy-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	ki	0.0001	uM
2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	40988: Inhibition on Benzodiazepine receptor	ic50	0.0001	uM
5-fluoro-2-[2-fluoro-5-[7-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]benzonitrile	259132: Displacement of [3H]Ro-151788 from human recombinant GABAA alpha5 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0001	uM
8-chloro-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73244: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-3-beta-3-gamma-2	ki	0.0001	uM
tert-butyl 8-hydroxy-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	ki	0.0001	uM
3-phenyl-6-(pyridazin-3-ylmethoxy)-[1,2,4]triazolo[3,4-a]phthalazine	72625: Binding affinity for human GABA-A receptor alpha-5-beta-3-gamma-2 subunits in L(tk-) cells	ki	0.0001	uM
2-[5-(7-ethyl-8-oxoimidazo[1,2-a]pyrazin-3-yl)-2-fluorophenyl]-5-fluorobenzonitrile	262297: Displacement of [3H]Ro-151788 from human recombinant GABA-Aalpha5 receptor plus beta3gamma2	ki	0.0001	uM
3,5-difluoro-2-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile	260334: Displacement of [3H]Ro 15-1788 from recombinant human GABAA alpha-1 receptor plus beta3gamma2 expressed in L(tk-) cells	ki	0.0001	uM
7-tert-butyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine	282667: Displacement of [3H]Ro 15-1788 from human recombinant GABAA alpha-3-beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
3-(2,6-difluorophenyl)-5-[4-fluoro-3-(3-fluoro-2-pyridinyl)phenyl]pyridazine	262644: Displacement of [3H]Ro-151788 from recombinant human GABA-Aalpha1 receptor plus beta3gamma2	ki	0.0001	uM
ethyl 6-methoxy-4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate	219791: Binding affinity measured using LtK- cell membranes expressing GABA alpha-1-beta-3-gamma-2 receptor	ki	0.0001	uM
2-(4-methylphenyl)-9-(2-thiophen-3-ylethyl)-6H-[1,2,4]triazolo[4,3-c]quinazoline-3,5-dione	552801: Displacement of [3H]flumazenil human recombinant alpha1beta3gamma2 GABA(A) receptor expressed in HEK293 cells after 30 mins by glass fiber filtration assay	ki	0.0001	uM
7-(2-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-thiophen-3-ylpyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
2-[3-[5-(2-hydroxypropan-2-yl)benzimidazol-1-yl]phenyl]benzonitrile	1604549: Displacement of [3H]-Ro15-1788 from human GABAA alpha5beta3gamma2 expressed in HEK293 cell membranes incubated for 40 or 90 mins by liquid scintillation counting method	ki	0.0001	uM
7-(2-fluorophenyl)-3-(furan-2-yl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]pyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
7-(2-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-thiophen-2-ylpyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
2-phenyl-3aH-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	ki	0.0001	uM
8-bromo-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	ki	0.0001	uM
4-[2-fluoro-5-[7-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]pyridine-3-carbonitrile	262147: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha5 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0001	uM
7-(2-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-pyridin-4-ylpyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
2-[2-fluoro-5-[8-fluoro-7-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]benzonitrile	262219: Displacement of [3H]Ro 15-1788 from human GABA-Aalpha1 receptor plus beta-3-gamma-2 expressed in mouse L(tk-) cells	ki	0.0002	uM
8-chloro-2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	1388015: Displacement of [3H]Ro15-1788 from human GABAA receptor alpha1beta3gamma2 expressed in LTK cells preincubated for 30 secs measured every 15 mins at -60 mV holding potential by two-electrode voltage clamp assay	ki	0.0002	uM
tert-butyl (7S)-14-bromo-12-oxo-2,4,11-triazatetracyclo[11.4.0.02,6.07,11]heptadeca-1(17),3,5,13,15-pentaene-5-carboxylate	73244: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-3-beta-3-gamma-2	ki	0.0002	uM
6-phenyl-9-[(2-propyl-1,2,4-triazol-3-yl)methoxy]-4,5,7,8-tetrazatetracyclo[9.2.2.02,10.03,7]pentadeca-2(10),3,5,8-tetraene	239566: Inhibition of [3H]Ro-151788 binding to recombinant human gamma-aminobutyric-acid A receptor alpha-5-beta-3-gamma-2 subtype expressed in L (tk-) cells	ki	0.0002	uM
9-[(1-benzylimidazol-2-yl)methoxy]-6-phenyl-4,5,7,8-tetrazatetracyclo[9.2.2.02,10.03,7]pentadeca-2(10),3,5,8-tetraene	239566: Inhibition of [3H]Ro-151788 binding to recombinant human gamma-aminobutyric-acid A receptor alpha-5-beta-3-gamma-2 subtype expressed in L (tk-) cells	ki	0.0002	uM
6-[(1-methylimidazol-2-yl)methoxy]-3-phenyl-[1,2,4]triazolo[3,4-a]phthalazine	72620: Binding affinity for human GABA-A receptor alpha-3-beta-3-gamma-2 subunits in L(tk-) cells	ki	0.0002	uM
9-[(3,5-dimethyl-2-pyridinyl)methoxy]-6-phenyl-4,5,7,8-tetrazatetracyclo[9.2.2.02,10.03,7]pentadeca-2(10),3,5,8-tetraene	239566: Inhibition of [3H]Ro-151788 binding to recombinant human gamma-aminobutyric-acid A receptor alpha-5-beta-3-gamma-2 subtype expressed in L (tk-) cells	ki	0.0002	uM
ethyl 15-methoxy-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carboxylate	448426: Binding affinity to GABAA alpha-5-beta-3-gamma-2 receptor	ki	0.0002	uM
ethyl 4-(methoxymethyl)-5-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0002	uM
2-(4-chlorophenyl)-6,7,8,9-tetrahydro-1H-pyrazolo[4,3-c]quinolin-3-one	221780: In vitro binding affinity against gamma-aminobutyric acid A receptor, alpha 1 expressed in L(tk) cells by displacement of [3H]Ro-151788	ki	0.0002	uM
2-(4-bromophenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	ki	0.0002	uM
3-(2,5-difluorophenyl)-7-(2-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]pyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0002	uM
3-(15-fluoro-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaen-5-yl)-5-methyl-1,2,4-oxadiazole	468635: Displacement of [3H]Flumazenil from cloned human GABA alpha-5-beta-3-gamma-2 receptor expressed in HEK293 cells	ki	0.0002	uM
ethyl 2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(17),3,5,9,11,13,15-heptaene-5-carboxylate	448426: Binding affinity to GABAA alpha-5-beta-3-gamma-2 receptor	ki	0.0002	uM
ethyl 15-chloro-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carboxylate	448426: Binding affinity to GABAA alpha-5-beta-3-gamma-2 receptor	ki	0.0002	uM
ethyl 15-fluoro-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carboxylate	468641: Displacement of [3H]Flumazenil from human GABA alpha-5-beta-3-gamma-2 receptor expressed in insect SF9 cells	ki	0.0002	uM
7-cyclobutyl-3-(2,6-difluorophenyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine	1604538: Displacement of [3H]-flumazenil from human GABAA alpha1beta3gamma2 expressed in Ltk cells	ki	0.0002	uM
15-(4-chlorophenyl)-13-(4-methyl-1,3-thiazol-2-yl)-4,11-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2(7),3,5,13-pentaen-12-one	72914: Displacement of [3H]Ro-151788 from human GABA-A receptor alpha-1-beta-3-gamma-2 subunits expressed in L(tk) cells	ki	0.0002	uM
2-(4-chlorophenyl)-8-(pyridin-4-ylmethyl)-1,5a,6,7,9,9a-hexahydropyrazolo[4,3-c][1,6]naphthyridin-3-one	221780: In vitro binding affinity against gamma-aminobutyric acid A receptor, alpha 1 expressed in L(tk) cells by displacement of [3H]Ro-151788	ki	0.0002	uM
3-fluoro-2-[2-fluoro-5-(7-methyl-8-oxoimidazo[1,2-a]pyrazin-3-yl)phenyl]benzonitrile	262295: Displacement of [3H]Ro-151788 from human recombinant GABA-Aalpha1 receptor plus beta3gamma2	ki	0.0002	uM
5-ethoxy-2,4,8,9-tetrazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(17),3,5,9,11,13,15-heptaene	448426: Binding affinity to GABAA alpha-5-beta-3-gamma-2 receptor	ki	0.0002	uM
4-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]pyridine-3-carbonitrile	262147: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha5 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0003	uM
4-fluoro-2-[2-fluoro-5-[7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]benzonitrile	259132: Displacement of [3H]Ro-151788 from human recombinant GABAA alpha5 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0003	uM
2-[3-(4-fluoro-3-pyridin-4-ylphenyl)imidazo[1,2-a]pyrimidin-7-yl]propan-2-ol	262147: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha5 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0003	uM
7-methoxy-2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	ki	0.0003	uM
tert-butyl 8-azido-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	ki	0.0003	uM
ethyl (7S)-14-bromo-11-oxo-2,4,10-triazatetracyclo[10.4.0.02,6.07,10]hexadeca-1(16),3,5,12,14-pentaene-5-carboxylate	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	ki	0.0003	uM
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

CTD chemical–gene interactions

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

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

ChEMBL screening assays

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

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2167730	Binding	Inhibition of [3H]R-(-)-14-induced receptor photolabeling at human FLAG-tagged beta3 GABA A receptor expressed in HEK293S cells at 200 uM relative to untreated control	Allyl m-trifluoromethyldiazirine mephobarbital: an unusually potent enantioselective and photoreactive barbiturate general anesthetic. — *J Med Chem*
CHEMBL4810229	ADMET	Inhibition of GABA A receptor (unknown origin) at 0.1 to 1 uM	Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. — *J Med Chem*
CHEMBL5335653	Toxicity	Antagonist activity at GABA-A (unknown origin)	Discovery of a Novel Bifunctional Steroid Analog, YXG-158, as an Androgen Receptor Degrader and CYP17A1 Inhibitor for the Treatment of Enzalutamide-Resistant Prostate Cancer. — *J Med Chem*

Cellosaurus cell lines

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

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

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

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 376 trials:

NCT	Phase	Status	Title
NCT01370486	Phase 4	WITHDRAWN	Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects
NCT02731300	Phase 4	COMPLETED	Transcranial Direct Current Stimulation, Treatment of Childhood Drug-Resistant Lennox-Gastaut Syndrome, A Pilot Study
NCT04133480	Phase 4	WITHDRAWN	Investigation of Cognitive Outcomes With Cannabidiol Oral Solution
NCT05044819	Phase 4	ACTIVE_NOT_RECRUITING	Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution
NCT06924827	Phase 4	NOT_YET_RECRUITING	A Study to Investigate the Transition of Children From ‘Artisanal Cannabidiol (CBD) to Epidiolex
NCT07728097	Phase 4	NOT_YET_RECRUITING	A Study to Investigate the Effect of Gradual Titration to Optimize Cannabidiol Treatment in Adults With LGS
NCT00124384	Phase 4	COMPLETED	The Effects of Modafinil on Waking Function and on Sleep in Individuals With Primary Insomnia
NCT00156533	Phase 4	COMPLETED	Long Term Treatment With Zolpidem: Nightly and Intermittent Dosing
NCT00178048	Phase 4	COMPLETED	Paroxetine in the Treatment of Chronic Primary Insomnia
NCT00235508	Phase 4	COMPLETED	Safety and Efficacy of Eszopiclone in Patients With Generalized Anxiety Disorder
NCT00252278	Phase 4	UNKNOWN	Effect of Atomoxetine on ADHD-Related Insomnia in Children and Adolescents
NCT00283790	Phase 4	COMPLETED	Residual Effects of Zolpidem Tartrate Extended Release and Eszopiclone Vs Placebo
NCT00287391	Phase 4	COMPLETED	Sleep Disorders and Gastroesophageal Reflux Disease (GERD)
NCT00295386	Phase 4	COMPLETED	Cognitive-Behavioural and Hypnotic Treatment of Chronic Primary Insomnia Among the Elderly
NCT00296179	Phase 4	COMPLETED	Ambien CR For Treatment Of Insomnia Associated With Depression When Used Concomitantly With Lexapro
NCT00296790	Phase 4	COMPLETED	Ambien CR vs. Placebo For Treatment Of Insomnia Associated With Anxiety When Used Concomitantly With Escitalopram (Lexapro)
NCT00337272	Phase 4	TERMINATED	Treating Chronic Insomnia in Breast Cancer Patients
NCT00359229	Phase 4	COMPLETED	Stilnox Treatment in Elderly Patients With Insomnia
NCT00365976	Phase 4	COMPLETED	Study of the Insomnia in Patients With Low Back Pain
NCT00386334	Phase 4	COMPLETED	A Long-Term Safety and Efficacy Study of Eszopiclone in Elderly With Primary Chronic Insomnia
NCT00392041	Phase 4	COMPLETED	Eszopiclone in the Treatment of Insomnia and Fibromyalgia
NCT00414037	Phase 4	TERMINATED	How do Sleeping Pills Affect Pain in the Brain?
NCT00414102	Phase 4	COMPLETED	Subjective Efficacy of Ramelteon on Sleep in Adults With Chronic Insomnia.
NCT00432198	Phase 4	COMPLETED	Zolpidem Postmarketing Study in Adolescent Patients With Insomnia
NCT00465972	Phase 4	COMPLETED	The Treatment of Insomnia in Patients With HIV Disease
NCT00492232	Phase 4	COMPLETED	Facilitation of Zolpidem (≥10 mg) Discontinuation Through Use of Ramelteon in Subjects With Chronic Insomnia
NCT00507546	Phase 4	COMPLETED	Functional Melatonin Replacement for Sleep Disruptions in Individuals With Tetraplegia
NCT00511134	Phase 4	TERMINATED	Study of Lunesta Versus Placebo for Sleep Problems Related to Smoking Cessation and Zyban
NCT00566371	Phase 4	COMPLETED	The Effect of a Once Daily Dose of Atomoxetine (ATX) on ADHD-Related Insomnia in Children and Adolescents
NCT00568789	Phase 4	COMPLETED	Safety of Ramelteon in Elderly Subjects
NCT00626210	Phase 4	TERMINATED	Modafinil Treatment for Sleep/Wake Disturbances in Older Adults
NCT00628914	Phase 4	UNKNOWN	Brain Mechanisms and Targeting Insomnia in Major Depression
NCT00653562	Phase 4	COMPLETED	Zolpidem (Myslee) Post Marketing Study in Adolescent Patients With Insomnia - Evaluation With Polysomnography
NCT00666796	Phase 4	COMPLETED	A Study to Assess the Pharmacodynamic Interaction Between Gabapentin and Ethanol in Healthy Subjects
NCT00723970	Phase 4	COMPLETED	Quetiapine Extended Release (XR) for the Treatment of Menopausal Depression
NCT00724282	Phase 4	COMPLETED	Treatment of Insomnia and Glucose Metabolism
NCT00812214	Phase 4	COMPLETED	Treatment of Insomnia in Migraineurs
NCT00813735	Phase 4	COMPLETED	Eszopiclone Co-Administered With Escitalopram for Insomnia in Elderly Adults With Major Depressive Disorder
NCT00826111	Phase 4	COMPLETED	The Effects of Eszopiclone and Lexapro on Prefrontal Glutamate and GABA in Depression With Anxiety and Insomnia
NCT00869934	Phase 4	COMPLETED	Cognitive-Behavior Therapy for Insomnia
NCT00889200	Phase 4	COMPLETED	Eszopiclone Treatment & Cortisol Responsivity
NCT00956319	Phase 4	COMPLETED	A Study to Evaluate Efficacy and Safety of Zolpidem Modified Release Formulation in Insomnia Patients
NCT01148186	Phase 4	TERMINATED	An Intervention Study to Reduce the Use and Impact of Potentially Inappropriate Medications Among Older Adults
NCT01156051	Phase 4	TERMINATED	Effect of Guanfacine Extended-Release on Attention Deficit Hyperactivity Disorder (ADHD)-Associated Insomnia
NCT01180855	Phase 4	UNKNOWN	Effects of Ramelteon (8mg) Alone and in Combination With Multi-Component Behavioral Therapy on Sleep and Circadian Phase in Patients With Chronic Insomnia
NCT01181232	Phase 4	COMPLETED	A Study to Compare Efficacy and Safety of Zolpidem Modified Release Formulation Versus Zolpidem in Insomnia Patients
NCT01207050	Phase 4	UNKNOWN	Effect of Rozerem on Sleep Among People With Traumatic Brain Injury
NCT01662297	Phase 4	TERMINATED	Comparison of Quetiapine and Trazodone Treatment for Insomnia in Dually Diagnosed Veterans
NCT01689909	Phase 4	COMPLETED	Reducing Suicidal Ideation Through Insomnia Treatment
NCT01896336	Phase 4	COMPLETED	Efficacy and Safety of 5 mg Sublingual Zolpidem vs 10mg Oral Zolpidem in the Induction and Maintenance of Sleep in Patients With Primary Insomnia
NCT02153788	Phase 4	COMPLETED	Efficacy and Safety of Temazepam in HIV Seropositive Patients With Insomnia
NCT02156271	Phase 4	COMPLETED	Mechanisms of Sleep Latency and Health: The Effect of a Melatonin Receptor Agonist in Inflammation and Insulin Resistance
NCT02456532	Phase 4	COMPLETED	Safety and Efficacy of Chronic Hypnotic Use 2
NCT02527564	Phase 4	COMPLETED	Efficacy of Suvorexant to Treat Insomnia Related to Bipolar Disorder
NCT02669030	Phase 4	UNKNOWN	A Six Week, Randomized, Double-Blind Placebo-Controlled, Suvorexant Augmentation Study of Antidepressant Treatment of Major Depressive Disorder With Residual Insomnia
NCT02669082	Phase 4	COMPLETED	The Exploratory Study to Investigate the Effect of Ramelteon for Insomnia Patients With Major Depressive Disorder by Using Actigraphy
NCT02684136	Phase 4	TERMINATED	Suvorexant in Insomnia Co-morbid With Fibromyalgia
NCT02704754	Phase 4	COMPLETED	Suvorexant and Trauma Related Insomnia
NCT02729714	Phase 4	COMPLETED	A Pilot Study of Suvorexant for Insomnia in Parkinson Disease
NCT02807922	Phase 4	COMPLETED	Pharmacological Treatment of Insomnia in Palliative Care

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for GABRB3 across ~30M SureChEMBL compounds — explore on Sugi Predict.