GABRA4

Summary

GABRA4 (gamma-aminobutyric acid type A receptor subunit alpha4, HGNC:4078) is a protein-coding gene on chromosome 4p12, encoding Gamma-aminobutyric acid receptor subunit alpha-4 (P48169). Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

Gamma-aminobutyric acid (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. This gene encodes subunit alpha-4, which is involved in the etiology of autism and eventually increases autism risk through interaction with another subunit, gamma-aminobutyric acid receptor beta-1 (GABRB1). Alternatively spliced transcript variants encoding different isoforms have been found in this gene.

Source: NCBI Gene 2557 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 75 total
• Druggable target: yes — 18 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000809

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4078
Approved symbol	GABRA4
Name	gamma-aminobutyric acid type A receptor subunit alpha4
Location	4p12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000109158
Ensembl biotype	protein_coding
OMIM	137141
Entrez	2557

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 nonsense_mediated_decay, 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000264318, ENST00000502874, ENST00000508560, ENST00000509316, ENST00000511523, ENST00000900310

RefSeq mRNA: 3 — MANE Select: NM_000809 NM_000809, NM_001204266, NM_001204267

CCDS: CCDS3473

Canonical transcript exons

ENST00000264318 — 9 exons

Exon	Start	End
ENSE00001256426	46993339	46993581
ENSE00001309008	46918900	46928755
ENSE00003494521	46992828	46992946
ENSE00003552799	46977061	46977143
ENSE00003581794	46979031	46979098
ENSE00003603991	46964970	46965229
ENSE00003614617	46977410	46977630
ENSE00003626940	46971083	46971235
ENSE00003627488	46974232	46974375

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 89.03.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.3460 / max 189.7951, expressed in 134 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52025	2.0383	128
52026	0.2446	78
52024	0.0631	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
postcentral gyrus	UBERON:0002581	89.03	gold quality
entorhinal cortex	UBERON:0002728	88.86	gold quality
buccal mucosa cell	CL:0002336	88.47	gold quality
parietal lobe	UBERON:0001872	87.89	gold quality
superior frontal gyrus	UBERON:0002661	87.64	gold quality
middle temporal gyrus	UBERON:0002771	86.00	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.54	gold quality
lateral nuclear group of thalamus	UBERON:0002736	85.39	silver quality
nucleus accumbens	UBERON:0001882	82.46	gold quality
endothelial cell	CL:0000115	82.29	gold quality
caudate nucleus	UBERON:0001873	81.48	gold quality
primary visual cortex	UBERON:0002436	80.57	gold quality
occipital lobe	UBERON:0002021	80.19	gold quality
putamen	UBERON:0001874	79.68	gold quality
prefrontal cortex	UBERON:0000451	79.07	gold quality
substantia nigra pars reticulata	UBERON:0001966	78.68	gold quality
frontal cortex	UBERON:0001870	78.51	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.45	gold quality
heart left ventricle	UBERON:0002084	78.37	gold quality
cardiac ventricle	UBERON:0002082	77.85	gold quality
neocortex	UBERON:0001950	77.45	gold quality
temporal lobe	UBERON:0001871	77.43	gold quality
telencephalon	UBERON:0001893	77.27	gold quality
cerebral cortex	UBERON:0000956	76.40	gold quality
apex of heart	UBERON:0002098	75.42	gold quality
forebrain	UBERON:0001890	74.90	gold quality
anterior cingulate cortex	UBERON:0009835	74.80	gold quality
Brodmann (1909) area 9	UBERON:0013540	74.75	gold quality
cingulate cortex	UBERON:0003027	74.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR3, SSRP1, TXK

miRNA regulators (miRDB)

433 targeting GABRA4, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-3P	99.99	70.75	2484

Literature-anchored findings (GeneRIF, showing 20)

• truncated alpha 4 N-terminus may play a post-translational regulatory role in intracellular folding/glycosylation/assembly of the alpha 4 subunit (PMID:12242096)
• GABRA4 is involved in the etiology of autism and potentially increases autism risk through interaction with GABRB1. (PMID:16080114)
• These results confirmed our earlier findings, indicating GABRA4 and GABRB1 as genes contributing to autism susceptibility, extending the effect to multiple ethnic groups and suggesting seizures as a stratifying phenotype. (PMID:16770606)
• alpha4beta3gamma2L receptors have unique kinetic properties that limit the range of GABA applications to which they can respond maximally. (PMID:17124266)
• Only two of the newly genotyped SNPs, rs10517173, rs16851647, were associated with nicotine dependence (observed P-values of 0.002, corrected FDR-BH P-values of 0.02). However, these SNPs were in complete LD with each other and with rs11731576. (PMID:19207358)
• Lower delta mRNA levels in schizophrenia might reflect a reduced number of alpha(1)beta(x)delta GABA(A) receptors that could contribute to deficient tonic inhibition and prefrontal cortical dysfunction in schizophrenia. (PMID:19289452)
• single nucleotide polymorphisms studied in the GABRA4, GABRE, and GABRQ genes are not related to the risk for familial ET. (PMID:21422964)
• Association between premenstrual symptom severity and two genes from the gamma-aminobutyric acid (GABA) pathway: steroid-5-alpha-reductase, alpha polypeptide 1 (SRD5A1) and gamma-aminobutyric acid receptor subunit alpha-4 (GABRA4). (PMID:22273344)
• The pathway by which GABRA2 initially confers risk for eventual alcohol problems begins with a predisposition to sensation-seeking early in adolescence. (PMID:23561058)
• Transgenic mice with the alpha4betadelta GABAA receptor subunit deletion show increased conditioned place preference, but not from delta-deficient or alpha4-deficient knockout mice. (PMID:24431441)
• The ability of neurosteroids to modulate the phosphorylation and membrane insertion of alpha4 subunit-containing GABAARs may underlie the profound effects these endogenous signaling molecules have on neuronal excitability and behavior. (PMID:24778259)
• GABRA4 is associated with autism spectrum disorder in a dataset from Argentina. (PMID:26239769)
• rs505474, rs1398175, and rs4868029 in the GABRA2, GABRA4, and GABRP genes, respectively, allele frequencies were significantly different between patients and controls.Four haplotypes were significantly associated with Bipolar Disorder TA and AG for rs3815762 and rs4868029 in GABRP, GG for rs11636988 and rs8024256 in GABRB3 and GAGG for rs2197414, rs4921195, rs13188991, and rs11956731 in GABRA6. (PMID:29135068)
• Study identified a rare noncoding sequence variants in gamma-aminobutyric acid A receptor, alpha 4 subunit in autism spectrum disorder. GABRA4 rare variants in noncoding DNA may be variants of modest physiological effects in ASD etiology. (PMID:29151244)
• GABRA4 rs2229940 did not show association with migraine risk (PMID:29299688)
• These results suggest association between GABRR3 rs832032 polymorphism and the risk for restless legs syndrome , and a modifier effect of GABRA4 rs2229940 on the age of onset of restless legs syndrome . (PMID:29720720)
• Steady-state activation of the high-affinity isoform of the alpha4beta2delta GABAA receptor. (PMID:31690811)
• Further evidence of GABRA4 and TOP3B as autism susceptibility genes. (PMID:32028044)
• A de novo missense variant in GABRA4 alters receptor function in an epileptic and neurodevelopmental phenotype. (PMID:35152403)
• De novo variants in GABRA4 are associated with a neurological phenotype including developmental delay, behavioral abnormalities and epilepsy. (PMID:38565639)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabra4	ENSDARG00000013389
mus_musculus	Gabra4	ENSMUSG00000029211
rattus_norvegicus	Gabra4	ENSRNOG00000002336

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), 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-4 — P48169 (reviewed: P48169)

Alternative names: GABA(A) receptor subunit alpha-4

All UniProt accessions (4): P48169, D6R924, D6RB66, X5D7F5

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. GABAARs containing alpha-4 are predominantly extrasynaptic, contributing to tonic inhibition in dentate granule cells and thalamic relay neurons. Extrasynaptic alpha-4-containing GABAARs control levels of excitability and network activity. GABAAR containing alpha-4-beta-3-delta subunits can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness.

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

Subcellular location. Cell membrane. Postsynaptic cell membrane.

Tissue specificity. Expressed in the brain.

Activity regulation. Potentiated by histamine.

Domain organisation. The GABA-binding pockets are located at the interface between neighboring alpha and beta subunits. 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.

Induction. The alpha-4 beta-2 gamma-2L receptor is not repressed by diazepam.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA4 sub-subfamily.

RefSeq proteins (3): NP_000800, NP_001191195, NP_001191196 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001390	GABAAa_rcpt	Family
IPR005434	GABBAa4_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 (57 total): strand 13, helix 11, topological domain 5, region of interest 4, transmembrane region 4, turn 4, glycosylation site 3, sequence variant 3, sequence conflict 3, compositionally biased region 2, binding site 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7QN5	ELECTRON MICROSCOPY	2.5
7QN9	ELECTRON MICROSCOPY	2.9
7QNC	ELECTRON MICROSCOPY	2.9
7QN7	ELECTRON MICROSCOPY	3
7QNA	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48169-F1	74.12	0.49

Antibody-complex structures (SAbDab): 5 — 7QN5, 7QN7, 7QN9, 7QNA, 7QNC

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): 100; 163

Disulfide bonds (1): 172–186

Glycosylation sites (3): 47, 144, 157

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-977443	GABA receptor activation

MSigDB gene sets: 237 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, BENPORATH_ES_WITH_H3K27ME3, TGCGCANK_UNKNOWN, GOBP_SYNAPSE_ASSEMBLY, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, AP2_Q3, GOBP_CELL_CELL_SIGNALING, chr4p12, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_CHLORIDE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION

GO Biological Process (9): gamma-aminobutyric acid signaling pathway (GO:0007214), central nervous system development (GO:0007417), synaptic transmission, GABAergic (GO:0051932), chloride transmembrane transport (GO:1902476), inhibitory synapse assembly (GO:1904862), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220), regulation of postsynaptic membrane potential (GO:0060078)

GO Molecular Function (9): GABA-A receptor activity (GO:0004890), benzodiazepine receptor activity (GO:0008503), GABA-gated chloride ion channel activity (GO:0022851), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), chloride channel activity (GO:0005254), signaling receptor activity (GO:0038023)

GO Cellular Component (10): plasma membrane (GO:0005886), dendrite membrane (GO:0032590), chloride channel complex (GO:0034707), postsynapse (GO:0098794), 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
nervous system development	1
system development	1
chemical synaptic transmission	1
chloride transport	1
monoatomic anion transmembrane transport	1
synapse assembly	1
transport	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
regulation of membrane potential	1
neurotransmitter receptor activity	1
chloride channel activity	1
ligand-gated monoatomic anion channel activity	1
regulation of postsynaptic membrane potential	1
signaling receptor activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
ligand-gated monoatomic ion channel activity	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
molecular transducer activity	1
membrane	1
cell periphery	1
dendrite	1
neuron projection membrane	1
monoatomic ion channel complex	1
postsynaptic membrane	1
postsynaptic specialization	1
GABA receptor complex	1
cell junction	1
postsynapse	1

Protein interactions and networks

STRING

1500 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRA4	GABRB1	P18505	785
GABRA4	EGR3	Q06889	701
GABRA4	SHANK3	Q9BYB0	640
GABRA4	IGBP1	P78318	624
GABRA4	NRXN1	Q9ULB1	591
GABRA4	KCNK3	O14649	552
GABRA4	GABBR2	O75899	547
GABRA4	SLC6A1	P30531	544
GABRA4	AUTS2	Q8WXX7	541
GABRA4	SLC6A4	P31645	534
GABRA4	SHANK2	Q9UPX8	498
GABRA4	CFAP74	Q9C0B2	490
GABRA4	GRM8	O00222	474
GABRA4	CDH10	Q9Y6N8	474
GABRA4	GABRA2	P47869	461

IntAct

8 interactions, top by confidence:

A	B	Type	Score
	GABRG2	psi-mi:“MI:0915”(physical association)	0.400
DGAT1	GABRA4	psi-mi:“MI:0915”(physical association)	0.370
GABRA4	GABRG2	psi-mi:“MI:0915”(physical association)	0.320
GABRA4	GABRD	psi-mi:“MI:0915”(physical association)	0.320

BioGRID (6): GABRA4 (Reconstituted Complex), GABRA4 (Synthetic Lethality), GABRA4 (Affinity Capture-Western), GABRA4 (Two-hybrid), APP (Reconstituted Complex), GABRA4 (Two-hybrid)

ESM2 similar proteins: D1LYT2, O00222, P08219, P08220, P0C2W5, P10063, P10064, P14867, P15431, P16305, P18505, P18507, P18508, P19019, P19150, P19969, P20236, P20237, P21548, P22300, P22723, P23574, P23576, P24045, P26049, P28471, P28472, P30191, P31644, P34903, P34904, P47743, P47870, P48169, P50571, P62812, P62813, P63079, P63080, P63137

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

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
GABRA4	“form complex”	“GABA-A (a4-b2-d) receptor”	binding
GABRA4	“form complex”	“GABA-A (a4-b3-d) receptor”	binding
GABRA4	“form complex”	“GABA-A (a4-b1-g2) receptor”	binding
PCDH19	“up-regulates quantity by stabilization”	GABRA4	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1886 predictions. Top by Δscore:

Variant	Effect	Δscore
4:46923643:A:C	donor_gain	1.0000
4:46965108:C:CT	acceptor_gain	1.0000
4:46965109:G:T	acceptor_gain	1.0000
4:46974228:TCA:T	donor_loss	1.0000
4:46974229:CA:C	donor_loss	1.0000
4:46974230:A:AG	donor_loss	1.0000
4:46974230:AC:A	donor_gain	1.0000
4:46974231:C:CG	donor_loss	1.0000
4:46974231:CC:C	donor_gain	1.0000
4:46974256:TTGA:T	donor_gain	1.0000
4:46974257:TGAT:T	donor_gain	1.0000
4:46974293:G:C	donor_gain	1.0000
4:46974371:GGCAT:G	acceptor_gain	1.0000
4:46974372:GCAT:G	acceptor_gain	1.0000
4:46974373:CAT:C	acceptor_gain	1.0000
4:46974373:CATC:C	acceptor_gain	1.0000
4:46974374:AT:A	acceptor_gain	1.0000
4:46974375:TCTAA:T	acceptor_loss	1.0000
4:46974376:C:CA	acceptor_loss	1.0000
4:46974376:C:CC	acceptor_gain	1.0000
4:46974377:T:A	acceptor_loss	1.0000
4:46977060:CAA:C	donor_gain	1.0000
4:46989426:T:TA	donor_gain	1.0000
4:46992845:AG:A	donor_gain	1.0000
4:46928342:A:AC	donor_gain	0.9900
4:46928343:C:CC	donor_gain	0.9900
4:46928754:TT:T	acceptor_gain	0.9900
4:46928756:C:CC	acceptor_gain	0.9900
4:46928768:A:C	acceptor_gain	0.9900
4:46964965:AATAC:A	donor_loss	0.9900

AlphaMissense

3628 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:46928278:A:G	W538R	1.000
4:46928278:A:T	W538R	1.000
4:46928310:G:T	P527Q	1.000
4:46965088:G:T	A339D	1.000
4:46965089:C:G	A339P	1.000
4:46965091:G:T	A338D	1.000
4:46965093:A:C	F337L	1.000
4:46965093:A:T	F337L	1.000
4:46965095:A:G	F337L	1.000
4:46965096:C:A	E336D	1.000
4:46965096:C:G	E336D	1.000
4:46965103:A:G	L334P	1.000
4:46965103:A:T	L334H	1.000
4:46965126:G:C	C326W	1.000
4:46965127:C:T	C326Y	1.000
4:46965128:A:G	C326R	1.000
4:46965138:G:C	F322L	1.000
4:46965138:G:T	F322L	1.000
4:46965140:A:G	F322L	1.000
4:46965145:T:A	D320V	1.000
4:46965145:T:C	D320G	1.000
4:46965145:T:G	D320A	1.000
4:46965146:C:G	D320H	1.000
4:46965151:G:T	A318D	1.000
4:46965195:G:C	S303R	1.000
4:46965195:G:T	S303R	1.000
4:46965197:T:G	S303R	1.000
4:46965199:A:G	L302P	1.000
4:46965214:A:G	L297P	1.000
4:46965214:A:T	L297H	1.000

dbSNP variants (sampled 300 via entrez): RS1000126171 (4:46925108 T>C), RS1000134884 (4:46980653 G>A), RS1000146631 (4:46968375 A>G), RS1000180890 (4:46964321 A>G), RS1000194297 (4:46982599 C>A,T), RS1000232214 (4:46952598 A>G), RS1000262299 (4:46925415 T>C), RS1000401795 (4:46946686 G>A,C), RS1000404627 (4:46985687 A>C), RS10004131 (4:46955159 C>A,G,T), RS10004359 (4:46918772 G>A,C), RS1000459203 (4:46919395 A>G), RS1000460314 (4:46940708 C>T), RS1000462711 (4:46923774 C>T), RS1000471623 (4:46958523 A>C,G)

Disease associations

OMIM: gene MIM:137141 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant
genetic developmental and epileptic encephalopathy	Limited	Autosomal dominant

Mondo (2): genetic developmental and epileptic encephalopathy (MONDO:0100062), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002123_1	Type 2 diabetes	1.000000e-06
GCST003901_4	Cognitive decline (age-related)	5.000000e-07
GCST006659_1	Polycystic ovary syndrome	2.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (11): CHEMBL2093872 (PROTEIN COMPLEX GROUP), CHEMBL2109243 (PROTEIN COMPLEX GROUP), CHEMBL2109244 (PROTEIN COMPLEX GROUP), CHEMBL2111366 (PROTEIN COMPLEX), CHEMBL2472 (SINGLE PROTEIN), CHEMBL3430899 (PROTEIN COMPLEX), CHEMBL4106157 (PROTEIN COMPLEX), CHEMBL4296046 (PROTEIN COMPLEX), CHEMBL4523639 (PROTEIN COMPLEX), CHEMBL4523640 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

18 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 478,322 (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
CHEMBL526	PROPOFOL	4	28,835
CHEMBL1522	ESZOPICLONE	4	6,548
CHEMBL4105630	ZURANOLONE	4	290
CHEMBL268254	DELORAZEPAM	2	1,308
CHEMBL275638	FLAVONE	2	88,985
CHEMBL287631	PROGABIDE	2	3,853
CHEMBL454095	ABECARNIL	2	566
CHEMBL8260	BAICALEIN	2	8,592
CHEMBL273481	MUSCIMOL	1	5,759
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1	160,188

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
flumazenil	Positive	7.03	pKi
cenobamate	Positive	4.38	pEC50

Binding affinities (BindingDB)

13 measured of 15 human assays (20 total across all organisms); most potent 13 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-(4-Methoxy-phenyl)-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one (CGS 9895)	KI	0.09 nM
2-Phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one (CGS 8216)	KI	0.11 nM
CGS-20625	KI	0.15 nM
CGS 9896	KI	0.26 nM
8-Bromo-7-oxo-3b,4,5,6-tetrahydro-7H-2,6a,11b-triaza-benzo[g]cyclopenta[e]azulene-3-carboxylic acid tert-butyl ester	KI	0.45 nM
Abecarnil	KI	4.4 nM
CAS_123662	KI	7.1 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
CAS_4375	KI	160 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
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

ChEMBL bioactivities

657 potent at pChembl≥5 of 706 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL454349
9.80	IC50	0.16	nM	CHEMBL309517
9.70	IC50	0.2	nM	CHEMBL4747460
9.62	IC50	0.24	nM	CHEMBL79037
9.40	IC50	0.3981	nM	CGS-8216
9.40	IC50	0.4	nM	CHEMBL1271047
9.34	IC50	0.46	nM	CHEMBL78730
9.31	IC50	0.49	nM	CHEMBL76263
9.30	IC50	0.5	nM	CHEMBL5266498
9.30	IC50	0.5	nM	CHEMBL5290464
9.30	IC50	0.5	nM	CHEMBL5280240
9.30	IC50	0.5	nM	CHEMBL49141
9.30	IC50	0.5	nM	CHEMBL1518572
9.22	IC50	0.6026	nM	CGS-9896
9.22	IC50	0.6	nM	CHEMBL419096
9.12	IC50	0.76	nM	CHEMBL540583
9.10	IC50	0.79	nM	CHEMBL77226
9.10	IC50	0.8	nM	CHEMBL5265845
9.10	IC50	0.8	nM	CHEMBL5291368
9.10	IC50	0.8	nM	CHEMBL5271392
9.07	Ki	0.85	nM	CLONAZEPAM
9.07	Ki	0.85	nM	Ro-151310
9.05	Ki	0.9	nM	FLUMAZENIL
9.05	IC50	0.9	nM	CHEMBL5285377
9.00	Ki	1	nM	CHEMBL3410222
9.00	IC50	1	nM	BETA-CCM
9.00	IC50	1	nM	CHEMBL454606
9.00	IC50	1	nM	CHEMBL1337028
9.00	IC50	1	nM	CHEMBL509197
9.00	IC50	1	nM	ABECARNIL
9.00	Ki	1	nM	CHEMBL54341
9.00	Ki	1	nM	CHEMBL348367
8.96	IC50	1.1	nM	CHEMBL444586
8.77	Ki	1.7	nM	CHEMBL154342
8.74	IC50	1.8	nM	CHEMBL444050
8.70	Ki	2	nM	FLUMAZENIL
8.70	IC50	2	nM	MUSCIMOL
8.66	IC50	2.2	nM	CHEMBL80610
8.64	IC50	2.3	nM	FIPRONIL
8.58	Ki	2.61	nM	CHEMBL471977
8.55	IC50	2.8	nM	CHEMBL75642
8.55	Ki	2.8	nM	CHEMBL372281
8.55	IC50	2.8	nM	DELORAZEPAM
8.52	Ki	3	nM	CHEMBL265547
8.52	IC50	3	nM	CHEMBL510764
8.52	IC50	3	nM	CHEMBL5266558
8.52	IC50	3	nM	CHEMBL2262044
8.52	IC50	3	nM	CHEMBL499814
8.52	IC50	3	nM	CHEMBL1161036
8.48	IC50	3.3	nM	CHEMBL75642

PubChem BioAssay actives

586 with measured affinity, of 1340 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	40988: Inhibition on Benzodiazepine receptor	ic50	0.0001	uM
ethyl 4-(methoxymethyl)-5-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0002	uM
ethyl 4-methyl-5-propan-2-yloxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0004	uM
2-phenyl-3aH-pyrazolo[4,3-c]quinolin-3-one	40988: Inhibition on Benzodiazepine receptor	ic50	0.0004	uM
ethyl 4-(methoxymethyl)-6-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
ethyl 4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
ethyl 6-methoxy-4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
ethyl 4-(methoxymethyl)-6-propoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
ethyl 6-hydroxy-4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0005	uM
2-(4-chlorophenyl)-3aH-pyrazolo[4,3-c]quinolin-3-one	40988: Inhibition on Benzodiazepine receptor	ic50	0.0006	uM
5-[[3-(1,3-benzodioxol-5-yl)-6-iminopyridazin-1-yl]methyl]-1,2-thiazol-3-one;hydrobromide	72153: Affinity for gamma-aminobutyric-acid A receptor measured by its ability to displace [3H]gabazine antagonist from rat brain preparations.	ic50	0.0008	uM
propan-2-yl 16-(methoxymethyl)-3,6,11,14-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-1(10),2,4,6,8,12,14,16-octaene-15-carboxylate	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0008	uM
ethyl 8-chloro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	533786: Binding affinity to human recombinant GABA alpha-4-beta-2-gamma-2 receptor	ki	0.0008	uM
propan-2-yl 4-(methoxymethyl)-6,9,14,21-tetrazapentacyclo[11.8.0.02,10.03,8.015,20]henicosa-1(21),2,4,6,8,10,12,15(20)-octaene-5-carboxylate	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0008	uM
propan-2-yl 15-(methoxymethyl)-4-propan-2-yl-5-oxa-10,13-diazatetracyclo[7.7.0.02,6.011,16]hexadeca-1(9),2(6),3,7,11,13,15-heptaene-14-carboxylate	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0008	uM
Clonazepam	239299: Displacement of [3H]flumazenil from bovine benzodiazepine receptor GABA-A channel of brain membranes	ki	0.0008	uM
15-(methoxymethyl)-14-(5-methyl-1,2-oxazol-3-yl)-4-propan-2-yl-5-oxa-3,10,13-triazatetracyclo[7.7.0.02,6.011,16]hexadeca-1(9),2(6),3,7,11,13,15-heptaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0009	uM
Flumazenil	239299: Displacement of [3H]flumazenil from bovine benzodiazepine receptor GABA-A channel of brain membranes	ki	0.0009	uM
ethyl 9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0010	uM
methyl 9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0010	uM
propyl 9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0010	uM
tert-butyl 9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0010	uM
7-chloro-5-methyl-3-(2-phenylethynyl)-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one	1196597: Displacement of [3H]flumazenil from rat cortex GABAA receptor BDZ binding site expressed in HEK293 cells by competition binding assay	ki	0.0010	uM
6-bromo-2-(3-nitrophenyl)chromen-4-one	72729: Binding affinity towards benzodiazepine site in GABAA receptor	ki	0.0010	uM
(2-methoxyphenyl)methyl 8-chloro-5-oxido-3,3a-dihydropyrazolo[5,1-c][1,2,4]benzotriazin-5-ium-3-carboxylate	41860: Binding affinity towards Benzodiazepine receptor from bovine brain membrane using [3H]Ro-151788 as radioligand	ki	0.0010	uM
propan-2-yl 4-(methoxymethyl)-6-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0010	uM
(2-methoxyphenyl)methyl 8-chloropyrazolo[5,1-c][1,2,4]benzotriazine-3-carboxylate	41860: Binding affinity towards Benzodiazepine receptor from bovine brain membrane using [3H]Ro-151788 as radioligand	ki	0.0017	uM
5-(aminomethyl)-1,2-oxazol-3-one	72155: Binding affinity in vivo for gamma-aminobutyric-acid A receptor measured by its ability to displace [3H]-GABA agonist from rat brain preparations after iv injection.	ic50	0.0020	uM
Fipronil	242615: In vitro insecticidal activity as inhibition of [3H]EBOB binding to Gamma-aminobutyric acid GABA-A receptor of housefly neuronal membranes	ic50	0.0023	uM
tert-butyl 5-methyl-6-oxo-8-(2-trimethylsilylethynyl)-3a,4-dihydro-1H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	343095: Binding affinity to GABAA alpha-4-beta-3-gamma-2 receptor	ki	0.0026	uM
9-chloro-2-phenyl-6H-triazolo[1,2-a][1,2,4]benzotriazine-1,5-dione	239299: Displacement of [3H]flumazenil from bovine benzodiazepine receptor GABA-A channel of brain membranes	ki	0.0028	uM
7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one	40974: In vitro displacement of [3H]-diazepam from GABA-A Benzodiazepine receptor	ic50	0.0028	uM
3-isothiocyanato-9H-pyrido[3,4-b]indole	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0030	uM
9H-pyrido[3,4-b]indole-3-carbonitrile	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0030	uM
3-(6,7-difluoro-1,3-benzoxazol-2-yl)-1,3a,4,5,6,7,8,8a-octahydrocyclohepta[d]imidazol-2-one	40986: Binding affinity against GABA-A benzodiazepine receptor	ki	0.0030	uM
(5aR,7R,9aS,11aS)-2-amino-7-hydroxy-9a,11a-dimethyl-3,3a,3b,4,5,5a,6,7,8,9,9b,11-dodecahydronaphtho[2,1-e]indol-10-one	72153: Affinity for gamma-aminobutyric-acid A receptor measured by its ability to displace [3H]gabazine antagonist from rat brain preparations.	ic50	0.0030	uM
3-propoxy-9H-pyrido[3,4-b]indole	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0030	uM
1-(9H-pyrido[3,4-b]indol-3-yl)butan-1-one	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0030	uM
ethyl 8-azido-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	1798656: Radioligand Binding Assay from Article 10.1021/jm800889m: “Structural Requirements for Eszopiclone and Zolpidem Binding to the gamma-Aminobutyric Acid Type-A (GABAA) Receptor Are Different.”	ki	0.0031	uM
8-fluoro-5-methyl-3-(2-phenylethynyl)-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one	1196597: Displacement of [3H]flumazenil from rat cortex GABAA receptor BDZ binding site expressed in HEK293 cells by competition binding assay	ki	0.0040	uM
methyl 6-hydroxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0040	uM
2-phenyl-6H-[1,2,4]triazolo[1,5-c]quinazolin-5-one	40986: Binding affinity against GABA-A benzodiazepine receptor	ki	0.0040	uM
17-chloro-9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0040	uM
5-nitro-9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0040	uM
5-bromo-9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0040	uM
17-methoxy-9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0040	uM
9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene	1932305: Inhibition of GABAA receptor (unknown origin)	ic50	0.0040	uM
methyl 6-(benzylamino)-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0040	uM
Diazepam	1934094: Inhibition of GABA-A receptor (unknown origin)	ic50	0.0042	uM
4-acetyl-13-(4-chlorophenyl)-5-thia-13,14-diazatricyclo[8.4.0.02,6]tetradeca-1(10),2(6),3-trien-12-one	40977: Binding affinity for GABA-A Benzodiazepine receptor	ki	0.0042	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
gamma-Aminobutyric Acid	increases reaction, decreases reaction, affects binding, increases activity	2
4-chloro-N-(2-(2-thienyl)imidazo(1,2-a)pyridin-3-yl)benzamide	increases activity, affects binding	1
tetramethylenedisulfotetramine	increases activity, affects binding, decreases reaction	1
arsenite	increases methylation	1
picrotoxinin	decreases reaction, increases activity, affects binding	1
benzamide	affects binding, increases activity, increases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
fipronil	affects binding, decreases activity	1
delta-hexachlorocyclohexane	affects binding, decreases activity	1
Resveratrol	affects cotreatment, decreases expression	1
Felbamate	affects binding, decreases activity	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Niclosamide	increases expression	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Pregnanolone	affects binding, increases activity	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Isotretinoin	decreases expression	1

ChEMBL screening assays

273 unique, capped per target: 233 binding, 36 functional, 3 toxicity, 1 admet

Representative assays (with source publication via chembl_document):

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

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1JM	PrecisION hGABAA alpha4/beta3/gamma2-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07531511	Not specified	NOT_YET_RECRUITING	SLC6A1-NDD Prospective Longitudinal Natural History Study
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP