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): 111 total — 6 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 70
• Druggable target: yes — 29 molecules with ChEMBL bioactivity
• 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: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000370314, ENST00000417858, ENST00000497894, ENST00000535043, ENST00000862742, ENST00000862743, ENST00000932320

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.

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

263 total, 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

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

97 targeting GABRA3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-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

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)

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), 1 shown:

• 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)

1 structures.

PDB	Method	Resolution (Å)
9CTP	ELECTRON MICROSCOPY	3.62

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab): 1 — 9CTP

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): 119; 182

Post-translational modifications (4): 426, 427, 433, 442

Disulfide bonds (1): 191–205

Glycosylation sites (4): 63, 163, 176, 228

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-977443	GABA receptor activation

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 (10): 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), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Neurotransmitter receptors and postsynaptic signal transmission	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GABA receptor activity	2
transmitter-gated monoatomic ion channel activity	2
synapse	2
cellular anatomical structure	2
synaptic membrane	2
cell-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
cell junction	1
postsynapse	1

Protein interactions and networks

STRING

1244 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRA3	ADAR	P55265	649
GABRA3	L1CAM	P32004	614
GABRA3	UBL4A	P11441	599
GABRA3	GRIA2	P42262	588
GABRA3	SLC32A1	Q9H598	586
GABRA3	FMR1	Q06787	562
GABRA3	GABBR2	O75899	558
GABRA3	GRIA3	P42263	557
GABRA3	CDKL5	O76039	542
GABRA3	CYFIP2	Q96F07	509
GABRA3	GRIA4	P48058	507
GABRA3	GABRB3	P28472	503
GABRA3	GRIK2	Q13002	499
GABRA3	EBP	Q15125	495
GABRA3	CDR2	Q01850	494

IntAct

7 interactions, top by confidence:

A	B	Type	Score
GABRA3	HLA-C	psi-mi:“MI:0914”(association)	0.530
GABRA3	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
UGT2B7	GABRA3	psi-mi:“MI:0915”(physical association)	0.370
SDCBP2	GABRA3	psi-mi:“MI:0915”(physical association)	0.370
GABRA3	GPAA1	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): GABRA3 (Affinity Capture-MS), GABRA5 (Affinity Capture-MS), ABCA7 (Affinity Capture-MS), SEC11C (Affinity Capture-MS), TMEM131 (Affinity Capture-MS), GLRB (Affinity Capture-MS), TUSC3 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TTC17 (Affinity Capture-MS), EDA (Affinity Capture-MS), POMT1 (Affinity Capture-MS), SPCS1 (Affinity Capture-MS), WLS (Affinity Capture-MS), ALG9 (Affinity Capture-MS)

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

Diamond homologs: A8MPY1, D1LYT2, F1R8P4, G5EBR3, O00591, O09028, O14764, O18276, O75311, O93430, P07727, P08219, P08220, P0C2W5, P10063, P10064, P14867, P15431, P16305, P18505, P18506, P18507, P18508, P19019, P19150, P19969, P20236, P20237, P20781, P21548, P22300, P22723, P22771, P22933, P23415, P23416, P23574, P23576, P24045, P24046

SIGNOR signaling

2 interactions.

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	54
Likely benign	12
Benign	3

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1342311	Single allele	Pathogenic
147589	GRCh38/hg38 Xq28(chrX:152371062-152569688)x0	Pathogenic
1799557	NM_000808.4(GABRA3):c.497C>T (p.Thr166Met)	Pathogenic
1799560	NM_000808.4(GABRA3):c.725A>T (p.Gln242Leu)	Pathogenic
3774414	GRCh37/hg19 Xq26.3-28(chrX:134810076-155258261)x1	Pathogenic
985441	NM_000808.4(GABRA3):c.1421A>G (p.Tyr474Cys)	Pathogenic
2576557	NM_000808.4(GABRA3):c.830A>G (p.Tyr277Cys)	Likely pathogenic

SpliceAI

2415 predictions. Top by Δscore:

Variant	Effect	Δscore
X:152168559:TTCTT:T	acceptor_gain	1.0000
X:152168560:TCTT:T	acceptor_loss	1.0000
X:152168561:CTT:C	acceptor_gain	1.0000
X:152168562:TT:T	acceptor_gain	1.0000
X:152168563:TCTAG:T	acceptor_loss	1.0000
X:152168564:C:CC	acceptor_gain	1.0000
X:152168565:T:G	acceptor_loss	1.0000
X:152168572:C:CT	acceptor_gain	1.0000
X:152168572:C:T	acceptor_gain	1.0000
X:152168573:A:T	acceptor_gain	1.0000
X:152168767:T:TA	donor_gain	1.0000
X:152197783:CTC:C	acceptor_gain	1.0000
X:152197786:C:CC	acceptor_gain	1.0000
X:152224761:A:AC	donor_gain	1.0000
X:152224761:ACAG:A	donor_gain	1.0000
X:152224762:C:CT	donor_gain	1.0000
X:152224762:CAG:C	donor_gain	1.0000
X:152224762:CAGC:C	donor_gain	1.0000
X:152224762:CAGCT:C	donor_gain	1.0000
X:152224767:T:TA	donor_gain	1.0000
X:152224844:ACCTA:A	acceptor_loss	1.0000
X:152224845:CCT:C	acceptor_loss	1.0000
X:152224846:C:CA	acceptor_loss	1.0000
X:152224846:C:CC	acceptor_gain	1.0000
X:152224847:T:G	acceptor_loss	1.0000
X:152251100:T:TA	donor_gain	1.0000
X:152255996:CTC:C	acceptor_gain	1.0000
X:152266281:T:C	donor_gain	1.0000
X:152284665:T:TG	donor_loss	1.0000
X:152284666:A:AC	donor_gain	1.0000

AlphaMissense

3239 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:152168284:A:G	W475R	1.000
X:152168284:A:T	W475R	1.000
X:152168316:G:C	P464R	1.000
X:152168316:G:T	P464H	1.000
X:152189793:G:C	N360K	1.000
X:152189793:G:T	N360K	1.000
X:152189803:G:T	A357D	1.000
X:152189805:A:C	F356L	1.000
X:152189805:A:T	F356L	1.000
X:152189806:A:C	F356C	1.000
X:152189807:A:G	F356L	1.000
X:152189815:A:G	L353P	1.000
X:152189838:A:C	C345W	1.000
X:152189839:C:T	C345Y	1.000
X:152189840:A:G	C345R	1.000
X:152189850:G:C	F341L	1.000
X:152189850:G:T	F341L	1.000
X:152189852:A:G	F341L	1.000
X:152189857:T:A	D339V	1.000
X:152189857:T:C	D339G	1.000
X:152189857:T:G	D339A	1.000
X:152189858:C:G	D339H	1.000
X:152189863:G:T	A337D	1.000
X:152189907:A:C	S322R	1.000
X:152189907:A:T	S322R	1.000
X:152189909:T:G	S322R	1.000
X:152189926:A:G	L316P	1.000
X:152189926:A:T	L316H	1.000
X:152189941:C:T	G311D	1.000
X:152197633:C:G	G311R	1.000

dbSNP variants (sampled 300 via entrez): RS1000016079 (X:152257848 A>C), RS1000021875 (X:152189223 C>A), RS1000024430 (X:152185313 T>C), RS1000030311 (X:152432684 T>C), RS1000047952 (X:152273442 T>C), RS1000053021 (X:152188738 A>G), RS1000065475 (X:152403498 A>T), RS1000084653 (X:152452776 T>C), RS1000085595 (X:152210099 T>C), RS1000086082 (X:152269788 A>C,G), RS1000128727 (X:152200101 T>C), RS1000132318 (X:152412353 A>C), RS1000159049 (X:152425138 C>T), RS1000170486 (X:152194336 T>A), RS1000228698 (X:152199812 C>G,T)

Disease associations

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

GenCC curated gene-disease

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

Mondo (3): syndromic X-linked intellectual disability Lubs type (MONDO:0010283), epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features (MONDO:0859564), partial deletion of the long arm of chromosome X (MONDO:0017007)

Orphanet (2): Proximal Xq28 duplication syndrome (Orphanet:1762), Partial deletion of the long arm of chromosome X syndrome (Orphanet:263756)

HPO phenotypes

70 total (30 of 70 shown, 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:0002153	Hyperkalemia
HP:0002203	Respiratory paralysis

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

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)

Molecules with ChEMBL bioactivity

29 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 530,254 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1082407	ENZALUTAMIDE	4	9,652
CHEMBL12	DIAZEPAM	4	92,281
CHEMBL1544	LIOTHYRONINE	4	23,700
CHEMBL1568698	GANAXOLONE	4	1,657
CHEMBL207538	BREXANOLONE	4	1,585
CHEMBL3183409	APALUTAMIDE	4	4,076
CHEMBL407	FLUMAZENIL	4	7,150
CHEMBL452	CLONAZEPAM	4	33,297
CHEMBL13280	FLUNITRAZEPAM	4	11,549
CHEMBL451	CHLORDIAZEPOXIDE	4	36,533
CHEMBL646	TRIAZOLAM	4	21,589
CHEMBL911	ZOLPIDEM	4	17,821
CHEMBL526	PROPOFOL	4	28,835
CHEMBL1522	ESZOPICLONE	4	6,548
CHEMBL661	ALPRAZOLAM	4	130,677
CHEMBL268254	DELORAZEPAM	2	1,308
CHEMBL275638	FLAVONE	2	88,985
CHEMBL287631	PROGABIDE	2	3,853
CHEMBL454095	ABECARNIL	2	566
CHEMBL8260	BAICALEIN	2	8,592
CHEMBL200177	MK-0777	2
CHEMBL3647536	DARIGABAT	2
CHEMBL366947	BRETAZENIL	2
CHEMBL279867	PANADIPLON	2
CHEMBL1783282	AZD7325	2
CHEMBL3681419	BASMISANIL	2
CHEMBL273481	MUSCIMOL	1
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1
CHEMBL1783256	AZD6280	1

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1112122	GABRA3		0.00	0
rs4828696	GABRA3		0.00	0
rs6627221	GABRA3		0.00	0
rs2201169	GABRA3		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

Most potent curated ligand interactions (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)

20 measured of 23 human assays (37 total across all organisms); most potent 20 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
8-Bromo-7-oxo-3b,4,5,6-tetrahydro-7H-2,6a,11b-triaza-benzo[g]cyclopenta[e]azulene-3-carboxylic acid tert-butyl ester	KI	0.45 nM
Halcion	KI	0.68 nM
FG 8205	KI	0.68 nM
Abecarnil	KI	4.4 nM
RO-154513	KI	10 nM
NSC_104999	KI	11.2 nM
ethyl 12-ethynyl-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,10,12-pentaene-5-carboxylate	KI	28.4 nM
P4S	KI	151 nM
5-({12-ethynyl-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,10,12-pentaen-5-yl}carbonyloxy)pentyl 12-ethynyl-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,11,13-pentaene-5-carboxylate	KI	231 nM
3-({12-ethynyl-9-phenyl-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,8,10,12-hexaen-5-yl}carbonyloxy)propyl 12-ethynyl-9-phenyl-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaene-5-carboxylate	KI	236 nM
NSC_93250	KI	236 nM
CAS_5448	KI	240 nM
ethyl 12-ethynyl-9-phenyl-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaene-5-carboxylate	KI	287 nM
4-[6-Amino-3-(4-methoxy-phenyl)-6H-pyridazin-1-yl]-butyric acid : bromide	KI	316 nM
CAS_64603-91-4	KI	1620 nM
Thio-4-PIOL	KI	1700 nM
3-({12-ethyl-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,10,12-pentaen-5-yl}carbonyloxy)propyl 12-ethyl-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,11,13-pentaene-5-carboxylate	KI	1850 nM
[({12-ethynyl-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,10,12-pentaen-5-yl}carbonyloxy)methoxy]methyl 12-ethynyl-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,11,13-pentaene-5-carboxylate	KI	3800 nM
DIAZEPAM	IC50	5600 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
NSC_130546	KI	7900 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

1364 with measured affinity, of 2560 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	affects binding, increases reaction	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)

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

Trial	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)