GABRA3

Summary

GABRA3 (gamma-aminobutyric acid type A receptor subunit alpha3, HGNC:4077) is a protein-coding gene on chromosome Xq28, encoding Gamma-aminobutyric acid receptor subunit alpha-3 (P34903). Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

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

Source: NCBI Gene 2556 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features (Definitive, GenCC)
• Clinical variants (ClinVar): 119 total — 6 pathogenic, 1 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 6 regions constrained (≈21% of expected missense variation)
• GTEx eGene: eQTL in 12 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 70
• Drug target: yes — 2 curated mechanism-of-action drugs, 1 via a complex or family; 29 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)
• MANE Select transcript: NM_000808

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4077
Approved symbol	GABRA3
Name	gamma-aminobutyric acid type A receptor subunit alpha3
Location	Xq28
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000011677
Ensembl biotype	protein_coding
OMIM	305660
Entrez	2556

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000370314

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

ENST00000370314, ENST00000417858, ENST00000497894, ENST00000535043, ENST00000862742, ENST00000862743, ENST00000932320, ENST00001076143, ENST00001076144, ENST00001116005, ENST00001133805

RefSeq mRNA: 1 — MANE Select: NM_000808 NM_000808

CCDS: CCDS14706

Canonical transcript exons

ENST00000370314 — 10 exons

Exon	Start	End
ENSE00000677768	152189730	152189941
ENSE00000677770	152208001	152208144
ENSE00000979805	152224763	152224845
ENSE00001131355	152284668	152284735
ENSE00001131364	152345581	152345702
ENSE00001320273	152451146	152451315
ENSE00001452358	152166234	152168563
ENSE00001452364	152364431	152364596
ENSE00001715116	152197633	152197785
ENSE00003706826	152255778	152255998

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 91.78.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6560 / max 112.2353, expressed in 273 samples.

Highest expression (Bgee): cortical plate, prefrontal cortex, cingulate cortex, male germ line stem cell (sensu Vertebrata) in testis, anterior cingulate cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GABRA3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	9.2e-16	-1.22	X:152210520:C:T
Skin Sun Exposed Lower leg	eqtl	6.7e-11	+0.34	X:152234430:C:A
Skin Not Sun Exposed Suprapubic	eqtl	4.9e-09	+0.33	X:152202635:T:C
Prostate	eqtl	3.8e-05	+0.32	X:152204898:C:T
Brain Nucleus accumbens basal ganglia	eqtl	1.4e-04	+0.68	X:151469510:C:A
Brain Substantia nigra	eqtl	1.9e-04	-0.84	X:153211378:G:A
Testis	eqtl	7.1e-04	-0.19	X:152112107:C:T
Colon Transverse	eqtl	8.1e-04	+0.21	X:152241621:G:A
Brain Anterior cingulate cortex BA24	eqtl	2.8e-03	-0.08	X:151688964:T:C
Small Intestine Terminal Ileum	eqtl	6.2e-03	-0.62	X:151465213:A:G
Minor Salivary Gland	eqtl	9.1e-03	-0.27	X:152239969:T:A
Brain Putamen basal ganglia	eqtl	1.9e-02	+0.44	X:152450250:C:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
200847	1.4676	259
200846	0.1477	69
200845	0.0224	11
200848	0.0183	8

Top tissues by expression

showing 100 of 263 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	91.78	gold quality
prefrontal cortex	UBERON:0000451	84.09	gold quality
cingulate cortex	UBERON:0003027	81.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.72	gold quality
anterior cingulate cortex	UBERON:0009835	81.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.24	gold quality
right frontal lobe	UBERON:0002810	80.02	gold quality
neocortex	UBERON:0001950	78.80	gold quality
frontal cortex	UBERON:0001870	78.76	gold quality
cerebral cortex	UBERON:0000956	76.62	gold quality
ventricular zone	UBERON:0003053	76.21	gold quality
ganglionic eminence	UBERON:0004023	75.36	gold quality
hypothalamus	UBERON:0001898	74.75	gold quality
amygdala	UBERON:0001876	74.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.61	gold quality
nucleus accumbens	UBERON:0001882	72.97	gold quality
telencephalon	UBERON:0001893	72.95	gold quality
Ammon’s horn	UBERON:0001954	72.47	gold quality
lateral nuclear group of thalamus	UBERON:0002736	71.72	silver quality
postcentral gyrus	UBERON:0002581	71.68	gold quality
superior frontal gyrus	UBERON:0002661	71.66	gold quality
temporal lobe	UBERON:0001871	70.31	gold quality
forebrain	UBERON:0001890	70.07	gold quality
buccal mucosa cell	CL:0002336	69.63	gold quality
entorhinal cortex	UBERON:0002728	67.99	gold quality
brain	UBERON:0000955	67.78	gold quality
central nervous system	UBERON:0001017	67.54	gold quality
parietal lobe	UBERON:0001872	67.48	gold quality
embryo	UBERON:0000922	64.82	gold quality
primary visual cortex	UBERON:0002436	64.45	gold quality
caudate nucleus	UBERON:0001873	63.32	gold quality
putamen	UBERON:0001874	63.05	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	62.55	gold quality
substantia nigra	UBERON:0002038	62.26	gold quality
Brodmann (1909) area 23	UBERON:0013554	61.37	gold quality
corpus callosum	UBERON:0002336	60.65	gold quality
spinal cord	UBERON:0002240	60.33	gold quality
midbrain	UBERON:0001891	60.11	gold quality
occipital lobe	UBERON:0002021	59.64	gold quality
right hemisphere of cerebellum	UBERON:0014890	57.94	gold quality
cerebellar cortex	UBERON:0002129	57.74	gold quality
cerebellar hemisphere	UBERON:0002245	57.50	gold quality
cerebellum	UBERON:0002037	56.65	gold quality
Brodmann (1909) area 46	UBERON:0006483	55.92	silver quality
middle temporal gyrus	UBERON:0002771	54.36	silver quality
islet of Langerhans	UBERON:0000006	53.98	gold quality
placenta	UBERON:0001987	50.79	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
lateral globus pallidus	UBERON:0002476	49.92	gold quality
quadriceps femoris	UBERON:0001377	49.88	gold quality
vastus lateralis	UBERON:0001379	49.52	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
orbitofrontal cortex	UBERON:0004167	49.28	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
esophagus mucosa	UBERON:0002469	49.08	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
oviduct epithelium	UBERON:0004804	48.70	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
endometrium	UBERON:0001295	48.30	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
epithelial cell of pancreas	CL:0000083	47.93	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
thymus	UBERON:0002370	47.84	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.74	gold quality
nasal cavity epithelium	UBERON:0005384	47.70	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	47.66	gold quality
renal glomerulus	UBERON:0000074	47.60	gold quality
uterine cervix	UBERON:0000002	47.55	gold quality
kidney epithelium	UBERON:0004819	47.32	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
diaphragm	UBERON:0001103	47.05	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
nephron tubule	UBERON:0001231	46.88	gold quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
cranial nerve II	UBERON:0000941	46.82	silver quality
deltoid	UBERON:0001476	46.15	gold quality
urinary bladder	UBERON:0001255	46.03	gold quality
layer of synovial tissue	UBERON:0007616	45.76	gold quality
nasal cavity mucosa	UBERON:0001826	45.54	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
endocervix	UBERON:0000458	45.00	gold quality
superior vestibular nucleus	UBERON:0007227	44.63	gold quality
ectocervix	UBERON:0012249	44.43	gold quality
smooth muscle tissue	UBERON:0001135	44.18	silver quality
duodenum	UBERON:0002114	43.70	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.39

HPA expression

RNA tissue specificity: Group enriched

51 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	106.1
Cerebral cortex	tissue	77.2	low
Somatosensory cortex	tissue	77.2
Occipital cortex	tissue	75.7
Prefrontal cortex	tissue	71.9
Retrosplenial and cingulate cortex	tissue	71.4
Hippocampal formation	tissue	71.3
Entorhinal cortex	tissue	71.3
Motor cortex	tissue	68.2
Retrosplenial cortex	tissue	67.9
Temporal cortex	tissue	65.3
Amygdala	tissue	58.2
Insular cortex	tissue	57.1
Choroid plexus	tissue	51.7
Substantia nigra	tissue	46.9
Postcentral gyrus	tissue	44.4
Septum	tissue	43.4
Hypothalamus	tissue	40.0
Midbrain	tissue	32.7
Caudate putamen	tissue	32.0
Thalamus	tissue	31.0
Ventral forebrain	tissue	30.7
Pons	tissue	29.7
Superior colliculi	tissue	24.6
Periaqueductal gray	tissue	23.9
Olfactory bulb	tissue	23.7
Basal ganglia	tissue	21.3	not detected
Locus coeruleus	tissue	21.2
Hippocampus	tissue	18.8	low
Medulla oblongata	tissue	18.6
Putamen	tissue	13.2
Spinal cord	tissue	13.1
Nucleus accumbens	tissue	9.9
Retina	tissue	8.3
Corpus callosum	tissue	5.9
Cerebellum	tissue	3.6	low
Placenta	tissue	2.7	not detected
Cervix	tissue	0.8	not detected
Testis	tissue	0.7	not detected
Seminal vesicle	tissue	0.6	not detected
Pituitary gland	tissue	0.5
Urinary bladder	tissue	0.4	not detected
Esophagus	tissue	0.3	not detected
Skin 1	tissue	0.2	not detected
Vagina	tissue	0.2	not detected
Endometrium 1	tissue	0.2	not detected
Colon	tissue	0.1	not detected
Small intestine	tissue	0.1	not detected
Duodenum	tissue	0.1	not detected
Prostate	tissue	0.1	not detected
Tonsil	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Subiculum (60.8), Ventral hippocampus (50.1), Arcuate nucleus (49.1), Dorsal hippocampus (45.3), Nucleus of the diagonal band (42.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting GABRA3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 97 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-11181-3P	99.75	66.38	2205

Functional genomics

Regional missense constraint (gnomAD)

ENST00000370314 splits into 6 regions with different missense tolerance; 1 is missense-constrained (≈21% 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
X:152,168,231–152,168,365	18 / 38.5	0.47	no
X:152,168,366–152,189,749	66 / 57.1	1.16	no
X:152,189,750–152,197,761	20 / 84.3	0.24	yes (p 2.5e-12)
X:152,197,762–152,208,030	18 / 16.4	1.09	no
X:152,208,031–152,284,700	42 / 116.2	0.36	no
X:152,284,701–152,364,570	69 / 79.4	0.87	no

Literature-anchored findings (GeneRIF, showing 26)

• extracellular domain models show subunit arrangement of GABA-A receptors (PMID:15033447)
• The results of our study indicate that GABRA 3 gene might also be involved in the genetic pathophysiology of unipolar major depressive disorder (PMID:15048654)
• 3 of GABRA3 are found to be associated with THPP (PMID:17970773)
• 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)
• Data show that GABRA3 is significant reductions in parietal cortex in subjects with autism. (PMID:18821008)
• GABRA3 gene was overexpressed in lung cancer and rarely expressed in other cancers (PMID:19048400)
• GABA and GABRA3 play important roles in hepatocellular carcinoma (HCC) development and progression and can be a promising molecular target for the development of new diagnostic and therapeutic strategies for HCC. (PMID:19084931)
• These findings suggest that common variation in the GABRA2, GABRA3, GABRA6, and GABRG2 genes does not play a major role in liability to anxiety spectrum disorders. (PMID:19842164)
• The ratios of beta(3)/beta(2) and alpha(5)/alpha(1) subunit protein expression in Angelman syndrome cortex were significantly decreased when compared with controls. (PMID:20692323)
• In subjects with schizophrenia, GABA A alpha3 receptor expression is 14% higher in layer 2 of the dorsolateral prefrontal cortex. (PMID:20843900)
• The results indicate that there may be specific GABA receptor gene expression variation in migraine, particularly involving the GABRA3 and GABBR2 genes. (PMID:21971078)
• 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)
• high expression of GABBR2 with a low expression of GABR(A3) may predict a better outcome in non-small cell lung cancer (PMID:23617850)
• Endogenous potentiation of GABAergic synaptic transmission and responses to GABA uncaging in the thalamic reticular nucleus is absent in mice in which benzodiazepine binding to alpha3 subunit-containing GABAARs is disrupted. (PMID:23727119)
• A novel role for GA-repeat core promoter to regulate gene expression in the genes such as GABRA3 involved in development and evolution. (PMID:24055488)
• The N-terminal region of GABRA3 and the GlyR beta subunit occupies the same binding site of gephyrin. (PMID:25531214)
• The alpha3-immunoreactivity in the cerebellar cortex was relatively weak, but it was abundantly observed in different cell populations in the subcortical cerebellar structures (PMID:26518133)
• Gabra3 activates the AKT pathway to promote breast cancer cell migration, invasion and metastasis. The A-to-I RNA-edited form of Gabra3 is found only in non-invasive breast cancers. Edited Gabra3 suppresses breast cancer cell invasion and metastasis. (PMID:26869349)
• GABRA3 induced MMP-2 and MMP-9 expression through activation of the JNK/AP-1 signaling pathway, promoting lymphatic metastasis in lung adenocarcinoma. (PMID:27081042)
• GABA alpha2 and/or alpha3 receptor subtypes are involved in GABAergic modulation of prolactin secretion. (PMID:27128218)
• These small-molecule GlyR PAMs have high potential both as early tool compounds to enable pharmacological studies of GlyR inhibitory neurotransmission and as a starting point for the development of potent, selective GlyRalpha3 PAMs as novel analgesics. (PMID:27412533)
• The GABRA3 found distribute in intercalated nucleui of amygdala and dentate gyrus. (PMID:29023704)
• Five missense variants and one microduplication were detected in four families and two sporadic cases presenting with a range of epileptic seizure types, a varying degree of intellectual disability and developmental delay, sometimes with dysmorphic features or nystagmus. (PMID:29053855)
• data indicate that the activation of CT-GABRA3 is correlated with that of MAGEA6. Therefore, MAGEA6 is linked with CT-GABRA3 through a bidirectional promoter. (PMID:31593956)
• The intracellular domain of GABRA3 and GABRB3 each contain essential anterograde trafficking signals that are required to overcome ER retention of assembled GABAA homo- or heteropentamers. (PMID:31610743)
• MiR-92b inhibited cells EMT by targeting Gabra3 and predicted prognosis of triple negative breast cancer patients. (PMID:31841197)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabra3	ENSDARG00000090883
mus_musculus	Gabra3	ENSMUSG00000031343
rattus_norvegicus	Gabra3	ENSRNOG00000056558

Paralogs (45): 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), HTR3D (ENSG00000186090), GABRA5 (ENSG00000186297), ZACN (ENSG00000186919), GABRD (ENSG00000187730), CHRNG (ENSG00000196811), GABRQ (ENSG00000268089)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95615) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased prepulse inhibition	2
increased locomotor activity	2
hyperactivity	1
increased startle reflex	1
abnormal GABA-mediated receptor currents	1

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
GABRE	protein-coding	2564
MIR105-1	ncRNA	406897
MAGEA10	protein-coding	4109
MIR452	ncRNA	574412
CSAG2	protein-coding	102723547
MIR105-2	ncRNA	406898
MAGEA3	protein-coding	4102
GABRQ	protein-coding	55879
MIR767	ncRNA	768215
MAGEA3-DT	ncRNA	105373370

Protein

Protein identifiers

Gamma-aminobutyric acid receptor subunit alpha-3 — P34903 (reviewed: P34903)

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

All UniProt accessions (1): P34903

UniProt curated annotations — full annotation on UniProt →

Function. Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain. GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission.

Subunit / interactions. Heteropentamer, formed by a combination of alpha (GABRA1-6), beta (GABRB1-3), gamma (GABRG1-3), delta (GABRD), epsilon (GABRE), rho (GABRR1-3), pi (GABRP) and theta (GABRQ) chains, each subunit exhibiting distinct physiological and pharmacological properties. Binds UBQLN1. Interacts with GPHN.

Subcellular location. Postsynaptic cell membrane. Cell membrane.

Disease relevance. Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features (EPILX2) [MIM:301091] A neurologic disorder characterized by variable combinations of epileptic seizure, and a varying degree of intellectual disability and developmental delay. Some patients have dysmorphic facial features or mild skeletal anomalies. In general, males are more severely affected than females, although there is evidence for incomplete penetrance in both sexes. The disease is caused by variants affecting the gene represented in this entry.

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

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. GABRA3 sub-subfamily.

RefSeq proteins (1): NP_000799* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001390	GABAAa_rcpt	Family
IPR005433	GABBAa3_rcpt	Family
IPR006028	GABAA/Glycine_rcpt	Family
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR018000	Neurotransmitter_ion_chnl_CS	Conserved_site
IPR036719	Neuro-gated_channel_TM_sf	Homologous_superfamily
IPR036734	Neur_chan_lig-bd_sf	Homologous_superfamily
IPR038050	Neuro_actylchol_rec	Homologous_superfamily
IPR047024	Gabra-1-6_TM	Domain

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea)

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

UniProt features (30 total): topological domain 5, sequence variant 5, modified residue 4, glycosylation site 4, transmembrane region 4, binding site 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures by resolution:

PDB	Title	Method	Resolution (Å)
9QJQ	GABA-A receptor a3b3 (1:4) + a3NB77(silent) + b3Mb125 + GABA	ELECTRON MICROSCOPY	2.63
9TNS	GABA-A receptor a3b3g2 + GABA-PRE + a3NB83	ELECTRON MICROSCOPY	2.8
9TNB	GABA-A receptor a3b3g2 + a3NB77 + bicuculline	ELECTRON MICROSCOPY	2.87
9TPQ	GABA-A receptor a3b3g2 + a3NB77 + GABA	ELECTRON MICROSCOPY	2.94
9QJP	GABA-A receptor a3b3g2 + a3NB83(PAM) + GABA	ELECTRON MICROSCOPY	3.22
9CTP	Native human GABAA receptor of beta2-alpha1-beta2-alpha3-gamma2 assembly	ELECTRON MICROSCOPY	3.62

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P34903-F1	77.23	0.56

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 9CTP

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted membrane proteins, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; nucleoplasm

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

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

Ligand- & substrate-binding residues (2)

Position	Role
119	4-aminobutanoate
182	4-aminobutanoate

Post-translational modifications (4)

Type	Positions
Phosphoserine	426, 433, 442
Phosphothreonine	427

Disulfide bonds (1)

Type	Positions
Disulfide bond	191–205

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	63, 163, 176, 228

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 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-112315	Transmission across Chemical Synapses	—

MSigDB gene sets: 318 (showing top): RRAGTTGT_UNKNOWN, GOBP_SYNAPSE_ASSEMBLY, GCANCTGNY_MYOD_Q6, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, TGACCTY_ERR1_Q2, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, CEBPB_01, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, MYOD_01, GOBP_CHLORIDE_TRANSPORT, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, GATA1_01

GO Biological Process (8): gamma-aminobutyric acid signaling pathway (GO:0007214), synaptic transmission, GABAergic (GO:0051932), chloride transmembrane transport (GO:1902476), inhibitory synapse assembly (GO:1904862), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220), regulation of postsynaptic membrane potential (GO:0060078)

GO Molecular Function (10): GABA-A receptor activity (GO:0004890), benzodiazepine receptor activity (GO:0008503), GABA-gated chloride ion channel activity (GO:0022851), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), chloride channel activity (GO:0005254), protein binding (GO:0005515), signaling receptor activity (GO:0038023)

GO Cellular Component (9): plasma membrane (GO:0005886), dendrite membrane (GO:0032590), chloride channel complex (GO:0034707), postsynapse (GO:0098794), GABA-ergic synapse (GO:0098982), postsynaptic specialization membrane (GO:0099634), GABA-A receptor complex (GO:1902711), membrane (GO:0016020), postsynaptic membrane (GO:0045211)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Neurotransmitter receptors and postsynaptic signal transmission	1
Transmission across Chemical Synapses	1
Neuronal System	1

GO top-level categories

37 GO namespaces:

Category	Terms
GABA receptor activity	2
transmitter-gated monoatomic ion channel activity	2
synapse	2
cellular anatomical structure	2
synaptic membrane	2
cell-cell signaling	1
chemical synaptic transmission	1
chloride transport	1
monoatomic anion transmembrane transport	1
synapse assembly	1
transport	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
regulation of membrane potential	1
neurotransmitter receptor activity	1
chloride channel activity	1
ligand-gated monoatomic anion channel activity	1
regulation of postsynaptic membrane potential	1
signaling receptor activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
ligand-gated monoatomic ion channel activity	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
binding	1
molecular transducer activity	1
membrane	1
cell periphery	1
dendrite	1
neuron projection membrane	1
monoatomic ion channel complex	1
postsynaptic membrane	1
postsynaptic specialization	1
GABA receptor complex	1
postsynapse	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
GABA-A receptor activity	MF	direct assay
GABA-gated chloride ion channel activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,060 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRA3	ADAR	P55265	628
GABRA3	UBL4A	P11441	600
GABRA3	L1CAM	P32004	595
GABRA3	GRIA2	P42262	581
GABRA3	SLC32A1	Q9H598	565
GABRA3	GABBR2	O75899	547
GABRA3	CDKL5	O76039	543
GABRA3	GRIA3	P42263	542
GABRA3	CYFIP2	Q96F07	541
GABRA3	FMR1	Q06787	540
GABRA3	GRIA4	P48058	498
GABRA3	AZIN1	O14977	498
GABRA3	EBP	Q15125	495
GABRA3	CDR2	Q01850	494
GABRA3	GRIA1	P42261	473

IntAct

Human interaction partners of GABRA3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
HLA-C	association	0.530	1
PIK3R1	physical association	0.400	1
SDCBP2	physical association	0.370	1
UGT2B7	physical association	0.370	1
GPAA1	association	0.350	1

BioGRID (45 interactions; top human partners by supporting records): ABCA7 (Affinity Capture-MS; 2 records), ALG9 (Affinity Capture-MS; 2 records), GABRA5 (Affinity Capture-MS; 2 records), GLRB (Affinity Capture-MS; 2 records), HLA-C (Affinity Capture-MS; 2 records), POMT1 (Affinity Capture-MS; 2 records), SEC11C (Affinity Capture-MS; 2 records), SLC47A1 (Affinity Capture-MS; 2 records), SPCS1 (Affinity Capture-MS; 2 records), TMEM131 (Affinity Capture-MS; 2 records), TMEM59L (Affinity Capture-MS; 2 records), TTC17 (Affinity Capture-MS; 2 records), TUSC3 (Affinity Capture-MS; 2 records), AMIGO1 (Affinity Capture-MS), EDA (Affinity Capture-MS)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
GABRA3	“form complex”	“GABA-A (a3-b1-g2) receptor”	binding
PCDH19	“up-regulates quantity by stabilization”	GABRA3	binding

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ GABRA3-GABRB1-GABRE-GABRQ complex	4	GABRA3, GABRB1, GABRE, GABRQ
★ GABRA3-GABRB1-GABRE complex	3	GABRA3, GABRB1, GABRE

Ligand–receptor pairs (CellPhoneDB) (3)

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

3 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
GABRA3;GABRB3;GABRE		Signaling by GABA
GABRA3;GABRB3;GABRG2		Signaling by GABA
GABRA3;GABRB3;GABRQ		Signaling by GABA

Disease & clinical

Genetic variants

Variant evidence for GABRA3: 119 ClinVar records (7 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	60
Likely benign	14
Benign	3

Top pathogenic / likely-pathogenic (7)

Showing all 7 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
985441	NM_000808.4(GABRA3):c.1421A>G (p.Tyr474Cys)	Pathogenic	criteria provided, single submitter	2
2576557	NM_000808.4(GABRA3):c.830A>G (p.Tyr277Cys)	Likely pathogenic	criteria provided, single submitter	1
1342311	Single allele	Pathogenic	criteria provided, single submitter	1
3774414	GRCh37/hg19 Xq26.3-28(chrX:134810076-155258261)x1	Pathogenic	criteria provided, single submitter	1
1799557	NM_000808.4(GABRA3):c.497C>T (p.Thr166Met)	Pathogenic	no assertion criteria provided	1
1799560	NM_000808.4(GABRA3):c.725A>T (p.Gln242Leu)	Pathogenic	no assertion criteria provided	1
147589	GRCh38/hg38 Xq28(chrX:152371062-152569688)x0	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore GABRA3’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; 38 predictions of 1,332):

Position(s)	Effect	Δscore	Sites
X:152168564–152168565	acceptor_loss	1.0000	6
X:152168572–152168573	acceptor_gain	1.0000	2
X:152224846–152224847	acceptor_loss	1.0000	6
X:152266281	donor_gain	1.0000
X:152284666–152284667	donor_loss	1.0000	5
X:152284736–152284737	acceptor_loss	1.0000	6
X:152284740	acceptor_gain	1.0000
X:152345579–152345580	donor_loss	1.0000	5
X:152345703–152345704	acceptor_loss	1.0000	4
X:152345710–152345711	acceptor_gain	1.0000	2

AlphaMissense

1,734 missense substitutions predicted likely pathogenic (of 3,239 scored), across 320 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
M110	9	0.976	1.000
M318	9	0.944	0.999
M183	9	0.933	0.994
M193	9	0.933	0.998
M288	9	0.932	0.999
M338	9	0.915	0.996
M200	9	0.894	0.997
D150	8	0.999	1.000
D201	8	0.999	1.000
D339	8	0.999	1.000
D79	8	0.998	1.000
D124	8	0.998	0.999
H162	8	0.998	1.000
D456	8	0.998	0.999
F297	8	0.997	1.000
D115	8	0.995	0.998
F153	8	0.993	0.999
F310	8	0.991	0.998
F350	8	0.990	0.999
F463	8	0.990	0.999

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Testicular Germ Cell Tumor)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	9.98e-05

Disease associations

OMIM: gene MIM:305660 | disease phenotypes: MIM:300260, MIM:301091

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features	Definitive	X-linked	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

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

Mondo (2): syndromic X-linked intellectual disability Lubs type (MONDO:0010283), epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features (MONDO:0859564)

Orphanet (1): Proximal Xq28 duplication syndrome (Orphanet:1762)

HPO phenotypes

showing 60 of 70 phenotypes (HPO-id order):

HPO	Term
HP:0000016	Urinary retention
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000278	Retrognathia
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000470	Short neck
HP:0000472	Long neck
HP:0000597	Ophthalmoparesis
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0000836	Hyperthyroidism
HP:0000975	Hyperhidrosis
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001337	Tremor
HP:0001417	X-linked inheritance
HP:0001513	Obesity
HP:0001657	Prolonged QT interval
HP:0001663	Ventricular fibrillation
HP:0001824	Weight loss
HP:0001962	Palpitations
HP:0002019	Constipation
HP:0002069	Bilateral tonic-clonic seizure
HP:0002121	Generalized non-motor (absence) seizure
HP:0002148	Hypophosphatemia
HP:0002153	Hyperkalemia
HP:0002203	Respiratory paralysis
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002384	Focal impaired awareness seizure
HP:0002445	Tetraplegia
HP:0002486	Myotonia
HP:0002917	Hypomagnesemia
HP:0003134	Abnormality of peripheral nerve conduction
HP:0003189	Long nose
HP:0003201	Rhabdomyolysis
HP:0003394	Muscle spasm
HP:0003457	EMG abnormality
HP:0003470	Paralysis
HP:0003552	Muscle stiffness
HP:0003621	Juvenile onset
HP:0003694	Late-onset proximal muscle weakness
HP:0003752	Episodic flaccid weakness
HP:0004303	Abnormal muscle fiber morphology
HP:0005165	Shortened PR interval
HP:0005709	2-3 toe cutaneous syndactyly
HP:0006670	Impaired myocardial contractility
HP:0007340	Lower limb muscle weakness
HP:0008153	Periodic hypokalemic paresis
HP:0008180	Mildly elevated creatine kinase
HP:0009020	Exercise-induced muscle fatigue
HP:0011097	Epileptic spasm
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0011706	Second degree atrioventricular block
HP:0011784	Thyrotoxicosis with diffuse goiter
HP:0011785	Thyrotoxicosis with toxic multinodular goiter

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C537723	Lubs X-linked mental retardation syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (10): CHEMBL2093872 (PROTEIN COMPLEX GROUP), CHEMBL2094120 (PROTEIN COMPLEX), CHEMBL2109243 (PROTEIN COMPLEX GROUP), CHEMBL2109244 (PROTEIN COMPLEX GROUP), CHEMBL2111339 (PROTEIN COMPLEX), CHEMBL3026 (SINGLE PROTEIN), CHEMBL3885572 (PROTEIN COMPLEX), CHEMBL3885573 (PROTEIN COMPLEX), CHEMBL3885574 (PROTEIN COMPLEX), CHEMBL3885575 (PROTEIN COMPLEX)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the GABRA3 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.

2 curated-mechanism drugs:

Drug	Modality	Max phase
AZD7325	Small molecule	2
AZD6280	Small molecule	1

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 GABRA3 — the drug acts on the assembly or class, not necessarily on this subunit alone.

1 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
ZOPICLONE	GABA-A receptor; agonist GABA site	9	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 440,880 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

29 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL661	ALPRAZOLAM	4	131,051
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
CHEMBL1522	ESZOPICLONE	4	6,627
CHEMBL407	FLUMAZENIL	4	7,208
CHEMBL13280	FLUNITRAZEPAM	4	11,627
CHEMBL1568698	GANAXOLONE	4	1,695
CHEMBL1544	LIOTHYRONINE	4	23,991
CHEMBL526	PROPOFOL	4	29,086
CHEMBL646	TRIAZOLAM	4	21,762
CHEMBL911	ZOLPIDEM	4	17,964
CHEMBL1783282	AZD7325	2	80
CHEMBL454095	ABECARNIL	2	566
CHEMBL8260	BAICALEIN	2	8,718
CHEMBL3681419	BASMISANIL	2	107
CHEMBL366947	BRETAZENIL	2	825
CHEMBL3647536	DARIGABAT	2
CHEMBL268254	DELORAZEPAM	2
CHEMBL275638	FLAVONE	2
CHEMBL200177	MK-0777	2
CHEMBL279867	PANADIPLON	2
CHEMBL287631	PROGABIDE	2
CHEMBL1783256	AZD6280	1
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1
CHEMBL273481	MUSCIMOL	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

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

Ligand	Action	Affinity	Parameter
CGS8216	Inverse agonist	9.92	pKi
flumazenil	Allosteric modulator	8.98	pKi
AZD7325	Positive	8.89	pKi
triazolam	Positive	8.84	pKi
clonazepam	Positive	8.7	pKi
ZK93423	Full agonist	8.4	pKi
flunitrazepam	Positive	7.8	pKi
diazepam	Positive	7.77	pKi
alprazolam	Positive	7.16	pEC50
zolpidem	Positive	5.67	pKi

Binding affinities (BindingDB)

764 measured of 859 human assays (871 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
PHENAZEPAM	KI	0.05 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
CHEMBL5280240	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
[3-(5-Cyclopropyl-[1,2,4]oxadiazol-3-yl)-6-fluoro-4H-imidazo[1,5-a]quinoxalin-5-yl]-morpholin-4-yl-methanone	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
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
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
[7-Chloro-3-(5-cyclopropyl-[1,2,4]oxadiazol-3-yl)-4H-imidazo[1,5-a]quinoxalin-5-yl]-morpholin-4-yl-methanone	KI	0.22 nM
CHEMBL4303594	KI	0.23 nM
4-amino-2-oxo-N-propyl-8-[6-(pyridin-3-ylmethoxy)-2-pyridinyl]-1H-quinoline-3-carboxamide	KI	0.23 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
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
CHEMBL3274851	KI	0.26 nM
6-Benzyl-4-oxo-1,4-dihydroquinoline-3-carboxylic Acid EthylEster	KI	0.27 nM
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
[3-(5-Cyclopropyl-[1,2,4]oxadiazol-3-yl)-7-fluoro-4H-imidazo[1,5-a]quinoxalin-5-yl]-morpholin-4-yl-methanone	KI	0.3 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
4-amino-8-[2-fluoro-5-(pyridin-2-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.3 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
4-amino-8-[2-fluoro-5-(1,3-oxazol-4-ylmethoxy)phenyl]-2-oxo-N-propyl-1H-quinoline-3-carboxamide	KI	0.3 nM	US-20250197368: 2-OXO-DIHYDROQUINOLINE-3-CARBOXAMIDE DERIVATIVES AS GABA TYPE A RECEPTOR MODULATORS
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
7-cyclopropyl-3-(2-fluorophenyl)-2-((2-methyl-2H-1,2,4-triazol-3-yl)methoxy)pyrazolo[1,5-d][1,2,4]triazine	KI	0.36 nM

ChEMBL bioactivities

1435 potent at pChembl≥5 of 1498 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
10.40	Ki	0.04	nM	CHEMBL3144849
10.30	Ki	0.05	nM	CHEMBL4243764
10.05	Ki	0.09	nM	CHEMBL3144841
10.00	IC50	0.1	nM	CHEMBL454349
10.00	Ki	0.1	nM	CHEMBL378761
10.00	Ki	0.1	nM	CHEMBL211704
9.96	Ki	0.11	nM	CHEMBL380110
9.92	Ki	0.12	nM	PHENAZEPAM
9.92	Ki	0.12	nM	CHEMBL3144615
9.92	Ki	0.12	nM	CGS-8216
9.85	Ki	0.14	nM	CHEMBL212008
9.85	Ki	0.14	nM	CHEMBL225631
9.80	IC50	0.16	nM	CHEMBL309517
9.77	Ki	0.17	nM	CHEMBL375742
9.70	Ki	0.2	nM	CHEMBL377556
9.70	Ki	0.2	nM	MK-0777
9.70	Ki	0.2	nM	CHEMBL4060185
9.70	IC50	0.2	nM	CHEMBL4747460
9.70	Ki	0.2	nM	BRETAZENIL
9.68	Ki	0.21	nM	CHEMBL4303594
9.66	Ki	0.22	nM	CHEMBL299210
9.62	IC50	0.24	nM	CHEMBL79037
9.60	Ki	0.25	nM	CHEMBL3144698
9.55	Ki	0.28	nM	CHEMBL383677
9.55	Ki	0.28	nM	CHEMBL209556
9.55	Ki	0.28	nM	CHEMBL3274851
9.52	Ki	0.3	nM	MK-0777
9.49	Ki	0.32	nM	CHEMBL202952
9.48	Ki	0.33	nM	CHEMBL199689
9.48	Ki	0.33	nM	CHEMBL416659
9.47	Ki	0.34	nM	CHEMBL381380
9.47	Ki	0.34	nM	CHEMBL224561
9.44	Ki	0.36	nM	CHEMBL208794
9.43	Ki	0.37	nM	CHEMBL199957
9.43	Ki	0.37	nM	CHEMBL300951
9.43	Ki	0.37	nM	CHEMBL300615
9.42	Ki	0.38	nM	CHEMBL382412
9.40	IC50	0.3981	nM	CGS-8216
9.40	Ki	0.4	nM	CHEMBL203286
9.40	IC50	0.4	nM	CHEMBL1271047
9.40	Ki	0.4	nM	CHEMBL295027
9.40	Ki	0.4	nM	CHEMBL44533
9.38	Ki	0.42	nM	CHEMBL203315
9.35	Kd	0.45	nM	FLUMAZENIL
9.35	Ki	0.45	nM	CHEMBL210510
9.34	IC50	0.46	nM	CHEMBL78730
9.34	Ki	0.46	nM	CHEMBL203591
9.33	Ki	0.47	nM	CHEMBL382173
9.31	IC50	0.49	nM	CHEMBL76263

PubChem BioAssay actives

1362 with measured affinity, of 2562 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	73244: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-3-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	73244: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-3-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
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
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
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
7-(2-fluorophenyl)-3-(furan-2-yl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]pyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
7-(2-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-thiophen-2-ylpyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
7-bromo-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one	1889908: Displacement of [3H]flunitrazepam from human recombinant alpha3beta2gamma2 GABAA receptor expressed in HEK cell membrane by competitive radioligand binding assay	ki	0.0001	uM
2-phenyl-3aH-pyrazolo[4,3-c]quinolin-3-one	73244: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-3-beta-3-gamma-2	ki	0.0001	uM
8-bromo-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
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
8-chloro-2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	1388019: Displacement of [3H]Ro15-1788 from human GABAA receptor alpha3beta3gamma2 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-[(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
ethyl 4-(methoxymethyl)-5-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0002	uM
3-(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
7-cyclobutyl-3-(2,6-difluorophenyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine	1604540: Displacement of [3H]-flumazenil from human GABAA alpha3beta3gamma2 expressed in Ltk cells	ki	0.0002	uM
7-cyclobutyl-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	0.0002	uM
7-tert-butyl-6-[(2-ethyl-1,2,4-triazol-3-yl)methoxy]-3-(2-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine	282667: Displacement of [3H]Ro 15-1788 from human recombinant GABAA alpha-3-beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0002	uM
2-[2-fluoro-5-[8-fluoro-7-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]benzonitrile	262220: Displacement of [3H]Ro 15-1788 from human GABA-Aalpha3 receptor plus beta-3-gamma-2 expressed in mouse L(tk-) cells	ki	0.0003	uM
6-[(6-methyl-2-pyridinyl)methoxy]-3-phenyl-[1,2,4]triazolo[3,4-a]phthalazine	73233: Binding affinity towards human gamma-aminobutyric-acid A receptor alpha-3-beta-3-gamma-2 using [3H]Ro-151788 expressed in L(tk-) cells	ki	0.0003	uM
7-cyclopentyl-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	0.0003	uM
7-bromo-5-(2-fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one	1889908: Displacement of [3H]flunitrazepam from human recombinant alpha3beta2gamma2 GABAA receptor expressed in HEK cell membrane by competitive radioligand binding assay	ki	0.0003	uM
2-(4-bromophenyl)-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	0.0003	uM
4-[2-fluoro-5-[7-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]pyridine-3-carbonitrile	262146: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha3 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0003	uM
7-(2-fluorophenyl)-3-(3-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	0.0003	uM
2-[3-[7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]benzonitrile	259131: Displacement of [3H]Ro-151788 from human recombinant GABAA alpha3 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0003	uM
2-[2-fluoro-5-[7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]benzonitrile	259131: Displacement of [3H]Ro-151788 from human recombinant GABAA alpha3 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0003	uM
3-fluoro-2-[2-fluoro-5-[7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]benzonitrile	259131: Displacement of [3H]Ro-151788 from human recombinant GABAA alpha3 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0004	uM
2-[3-[4-fluoro-3-(3-fluoro-2-pyridinyl)phenyl]imidazo[1,2-a]pyrimidin-7-yl]propan-2-ol	262146: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha3 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0004	uM
13-(4-methyl-1,3-thiazol-2-yl)-15-phenyl-4,11-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2(7),3,5,13-pentaen-12-one	73231: Binding affinity at human recombinant gamma-aminobutyric-acid A receptor alpha-3-beta-3-gamma-2 expressed in L(tk) cells by [3H]Ro-151788 displacement.	ki	0.0004	uM
3-phenyl-6-(pyridazin-3-ylmethoxy)-[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	0.0004	uM
10-methyl-3-phenyl-6-(pyridin-2-ylmethoxy)-[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	0.0004	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
3-(2,6-difluorophenyl)-5-[4-fluoro-3-(3-fluoro-2-pyridinyl)phenyl]pyridazine	262645: Displacement of [3H]Ro-151788 from recombinant human GABA-Aalpha3 receptor plus beta3gamma2	ki	0.0004	uM
7-cyclopropyl-3-(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	0.0004	uM
Flumazenil	726250: Binding affinity to human GABAA alpha3beta2gamma2 expressed in thymidine kinase-deficient L cells	kd	0.0004	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	73231: Binding affinity at human recombinant gamma-aminobutyric-acid A receptor alpha-3-beta-3-gamma-2 expressed in L(tk) cells by [3H]Ro-151788 displacement.	ki	0.0004	uM
2-[3-(7-methylimidazo[1,2-a]pyrimidin-3-yl)phenyl]benzonitrile	259131: Displacement of [3H]Ro-151788 from human recombinant GABAA alpha3 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0004	uM
3,7-bis(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	0.0004	uM
2-[7-(4-fluoro-3-pyridin-4-ylphenyl)imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol	262146: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha3 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0005	uM
13-(4-methyl-1,3-thiazol-2-yl)-15-pyridin-4-yl-4,11-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2(7),3,5,13-pentaen-12-one	726246: Positive allosteric modulation of GABAA alpha3 (unknown origin)	ki	0.0005	uM
2-[6-[7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl]-2-pyridinyl]benzonitrile	261198: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha3 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0005	uM
tert-butyl 8-hydroxy-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	219954: Binding affinity against alpha-3-beta-3-gamma-2 GABAA/BzR receptor subtype.	ki	0.0005	uM
[3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-6-fluoro-4H-imidazo[1,5-a]quinoxalin-5-yl]-morpholin-4-ylmethanone	73226: Displacement of [3H]flunitrazepam from GABA-A receptor alpha-3-beta-2-gamma-2 subunits expressed in Sf9 cells	ki	0.0005	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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
ethyl-p-hydroxybenzoate	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	increases reaction, affects binding	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Estradiol	increases expression	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
Vanadates	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

400 unique, capped per target: 324 binding, 70 functional, 3 admet, 3 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3363914	Binding	Displacement of [3H]Muscimol from rat GABAA receptor at 10 uM after 90 mins by microbeta counting analysis	Griseorhodins D-F, neuroactive intermediates and end products of post-PKS tailoring modification in Griseorhodin biosynthesis. — *J Nat Prod*
CHEMBL4810229	ADMET	Inhibition of GABA A receptor (unknown origin) at 0.1 to 1 uM	Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. — *J Med Chem*
CHEMBL5335653	Toxicity	Antagonist activity at GABA-A (unknown origin)	Discovery of a Novel Bifunctional Steroid Analog, YXG-158, as an Androgen Receptor Degrader and CYP17A1 Inhibitor for the Treatment of Enzalutamide-Resistant Prostate Cancer. — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1JL	PrecisION hGABAA alpha3/beta3/gamma2-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

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

2 trials:

NCT	Phase	Status	Title
NCT03077308	Not specified	COMPLETED	Rare Diseases Clinical Research Network: Neurophysiological Correlates
NCT06615206	Not specified	RECRUITING	A First-in-Human Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of a Novel CRISPR RNA-editing Therapy in Patients with Mecp2 Duplication Syndrome, a Rare Orphan Disease (HERO)

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for GABRA3 across ~30M SureChEMBL compounds — explore on Sugi Predict.