GABRG2

Summary

GABRG2 (gamma-aminobutyric acid type A receptor subunit gamma2, HGNC:4087) is a protein-coding gene on chromosome 5q34, encoding Gamma-aminobutyric acid receptor subunit gamma-2 (P18507). Gamma subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammlian brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene have been associated with epilepsy and febrile seizures. Multiple transcript variants encoding different isoforms have been identified for this gene.

Source: NCBI Gene 2566 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epilepsy (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 821 total — 82 pathogenic, 60 likely-pathogenic (top 4% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈27% of expected missense variation)
• GTEx eGene: eQTL in 6 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 143
• Drug target: yes — 2 via a complex or family; 55 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs acting on a complex or family including it: 2 — Zaleplon, Zolpidem Tartrate (GABA A receptor alpha-1/beta-1/gamma-2)
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.43 (moderately constrained)
• MANE Select transcript: NM_198904

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4087
Approved symbol	GABRG2
Name	gamma-aminobutyric acid type A receptor subunit gamma2
Location	5q34
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000113327
Ensembl biotype	protein_coding
OMIM	137164
Entrez	2566

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 19 protein_coding, 6 nonsense_mediated_decay, 4 retained_intron, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000639213

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 3, TSL 3: 3, TSL 5: 19

ENST00000639213, ENST00000356592, ENST00000361925, ENST00000414552, ENST00000522053, ENST00000522990, ENST00000523372, ENST00000638253, ENST00000638552, ENST00000638660, ENST00000638772, ENST00000638782, ENST00000638877, ENST00000639046, ENST00000639111, ENST00000639278, ENST00000639384, ENST00000639424, ENST00000639549, ENST00000639554, ENST00000639683, ENST00000639975, ENST00000640500, ENST00000640574, ENST00000640739, ENST00000640757, ENST00000640910, ENST00000640985, ENST00000641017, ENST00000943443, ENST00000943444, ENST00001136221

RefSeq mRNA: 15 — MANE Select: NM_198904 NM_000816, NM_001375339, NM_001375340, NM_001375341, NM_001375342, NM_001375343, NM_001375344, NM_001375345, NM_001375346, NM_001375347, NM_001375348, NM_001375349, NM_001375350, NM_198903, NM_198904

CCDS: CCDS4358, CCDS4359, CCDS47333, CCDS93812, CCDS93813, CCDS93814, CCDS93815, CCDS93816

Canonical transcript exons

ENST00000639213 — 10 exons

Exon	Start	End
ENSE00001422058	162151730	162151753
ENSE00003477526	162095495	162095562
ENSE00003477712	162149108	162149313
ENSE00003535086	162097638	162097858
ENSE00003536104	162101235	162101317
ENSE00003610094	162142164	162142316
ENSE00003625954	162103889	162104026
ENSE00003654309	162093828	162093979
ENSE00003809373	162153093	162155526
ENSE00003809572	162067773	162068106

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 99.09.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 6.3357 / max 775.0952, expressed in 135 samples.

Highest expression (Bgee): middle temporal gyrus, Brodmann (1909) area 23, superior frontal gyrus, primary visual cortex, postcentral gyrus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GABRG2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

6 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Frontal Cortex BA9	eqtl	3.6e-03	+0.41	5:162773512:G:A
Brain Cortex	eqtl	8.3e-03	+0.41	5:162184380:T:TG
Pituitary	eqtl	9.1e-03	-1.67	5:162271757:G:A
Brain Cerebellum	eqtl	3.1e-02	-0.15	5:161815953:C:T
Brain Putamen basal ganglia	eqtl	3.2e-02	+0.26	5:161635170:A:C
Brain Hypothalamus	eqtl	5.0e-02	+0.36	5:162004386:C:T

FANTOM5 promoters

showing 10 of 15 alternative TSS:

Promoter ID	TPM avg	Samples expressed
59960	2.1026	112
59959	1.1804	104
59953	0.7889	101
59949	0.5050	96
59952	0.4074	93
59955	0.3138	65
59950	0.2774	74
59958	0.1633	66
59954	0.1569	59
59957	0.1387	54

Top tissues by expression

showing 100 of 283 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.09	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.46	gold quality
superior frontal gyrus	UBERON:0002661	96.66	gold quality
primary visual cortex	UBERON:0002436	96.52	gold quality
postcentral gyrus	UBERON:0002581	96.38	gold quality
parietal lobe	UBERON:0001872	96.23	gold quality
frontal pole	UBERON:0002795	96.18	gold quality
occipital lobe	UBERON:0002021	95.58	gold quality
pons	UBERON:0000988	95.34	gold quality
prefrontal cortex	UBERON:0000451	95.06	gold quality
endothelial cell	CL:0000115	94.93	gold quality
entorhinal cortex	UBERON:0002728	94.86	gold quality
superior vestibular nucleus	UBERON:0007227	94.74	gold quality
frontal cortex	UBERON:0001870	94.18	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.17	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.66	gold quality
cerebellar vermis	UBERON:0004720	93.56	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.50	gold quality
neocortex	UBERON:0001950	93.11	gold quality
cerebellar cortex	UBERON:0002129	92.48	gold quality
cerebellum	UBERON:0002037	92.43	gold quality
cerebral cortex	UBERON:0000956	92.41	gold quality
cerebellar hemisphere	UBERON:0002245	92.38	gold quality
right frontal lobe	UBERON:0002810	92.00	gold quality
paraflocculus	UBERON:0005351	91.75	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.71	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.57	gold quality
cingulate cortex	UBERON:0003027	90.34	gold quality
anterior cingulate cortex	UBERON:0009835	90.31	gold quality
telencephalon	UBERON:0001893	89.87	gold quality
nucleus accumbens	UBERON:0001882	89.60	gold quality
cortical plate	UBERON:0005343	89.46	gold quality
forebrain	UBERON:0001890	88.68	gold quality
temporal lobe	UBERON:0001871	88.67	gold quality
hypothalamus	UBERON:0001898	88.64	gold quality
substantia nigra pars compacta	UBERON:0001965	88.59	gold quality
brain	UBERON:0000955	88.52	gold quality
lateral globus pallidus	UBERON:0002476	88.18	gold quality
central nervous system	UBERON:0001017	87.92	gold quality
Ammon’s horn	UBERON:0001954	87.47	gold quality
orbitofrontal cortex	UBERON:0004167	87.26	gold quality
Brodmann (1909) area 10	UBERON:0013541	86.52	gold quality
ventral tegmental area	UBERON:0002691	85.52	gold quality
amygdala	UBERON:0001876	84.42	gold quality
caudate nucleus	UBERON:0001873	84.24	gold quality
substantia nigra pars reticulata	UBERON:0001966	82.84	gold quality
putamen	UBERON:0001874	82.33	gold quality
dorsal root ganglion	UBERON:0000044	81.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.83	gold quality
medulla oblongata	UBERON:0001896	80.22	gold quality
middle frontal gyrus	UBERON:0002702	79.81	silver quality
adult organism	UBERON:0007023	79.69	gold quality
midbrain	UBERON:0001891	79.05	gold quality
substantia nigra	UBERON:0002038	78.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.96	gold quality
pituitary gland	UBERON:0000007	77.05	gold quality
trigeminal ganglion	UBERON:0001675	76.32	gold quality
dorsal plus ventral thalamus	UBERON:0001897	75.94	gold quality
adenohypophysis	UBERON:0002196	74.98	gold quality
islet of Langerhans	UBERON:0000006	73.72	gold quality
globus pallidus	UBERON:0001875	70.63	gold quality
ganglionic eminence	UBERON:0004023	70.18	gold quality
spinal cord	UBERON:0002240	69.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	69.09	gold quality
medial globus pallidus	UBERON:0002477	68.15	gold quality
ventricular zone	UBERON:0003053	66.47	gold quality
inferior vagus X ganglion	UBERON:0005363	66.42	gold quality
corpus callosum	UBERON:0002336	65.11	gold quality
subthalamic nucleus	UBERON:0001906	62.24	gold quality
embryo	UBERON:0000922	61.54	gold quality
CA1 field of hippocampus	UBERON:0003881	61.08	silver quality
endometrium epithelium	UBERON:0004811	60.62	gold quality
tibialis anterior	UBERON:0001385	56.90	silver quality
oocyte	CL:0000023	56.56	gold quality
decidua	UBERON:0002450	56.55	gold quality
rectum	UBERON:0001052	54.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	54.47	silver quality
muscle layer of sigmoid colon	UBERON:0035805	53.91	gold quality
pancreas	UBERON:0001264	53.85	gold quality
ileal mucosa	UBERON:0000331	53.75	silver quality
hair follicle	UBERON:0002073	52.43	gold quality
quadriceps femoris	UBERON:0001377	52.34	gold quality
thymus	UBERON:0002370	52.28	gold quality
vermiform appendix	UBERON:0001154	51.73	gold quality
sigmoid colon	UBERON:0001159	51.45	gold quality
right adrenal gland	UBERON:0001233	51.36	gold quality
vastus lateralis	UBERON:0001379	51.16	gold quality
choroid plexus epithelium	UBERON:0003911	50.87	silver quality
deltoid	UBERON:0001476	50.78	gold quality
anatomical system	UBERON:0000467	50.70	gold quality
multicellular organism	UBERON:0000468	50.58	gold quality
material anatomical entity	UBERON:0000465	50.57	gold quality
caecum	UBERON:0001153	50.26	gold quality
adrenal gland	UBERON:0002369	49.63	gold quality
colonic epithelium	UBERON:0000397	49.62	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
leukocyte	CL:0000738	49.27	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
colon	UBERON:0001155	48.89	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	238.27
E-HCAD-35	yes	59.20
E-HCAD-25	yes	8.88
E-ANND-3	yes	7.45
E-GEOD-84465	yes	6.56
E-GEOD-137537	yes	6.08

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 71 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Frontal cortex	tissue	168.1
Cerebral cortex	tissue	121.2
Occipital cortex	tissue	121.2
Somatosensory cortex	tissue	120.0
Caudate putamen	tissue	100.1
Retrosplenial and cingulate cortex	tissue	92.5
Motor cortex	tissue	90.9
Hippocampal formation	tissue	87.6
Entorhinal cortex	tissue	87.6
Prefrontal cortex	tissue	87.1
Pons	tissue	85.6
Temporal cortex	tissue	80.4
Hypothalamus	tissue	79.4
Retrosplenial cortex	tissue	76.4
Thalamus	tissue	75.1
Superior colliculi	tissue	71.9
Postcentral gyrus	tissue	71.8
Midbrain	tissue	70.8
Septum	tissue	70.2
Cerebellum	tissue	70.0
Insular cortex	tissue	64.7
Locus coeruleus	tissue	52.0
Ventral forebrain	tissue	51.7
Periaqueductal gray	tissue	51.7
Substantia nigra	tissue	47.2
Putamen	tissue	47.0
Amygdala	tissue	45.3
Olfactory bulb	tissue	42.4
Basal ganglia	tissue	40.2
Medulla oblongata	tissue	36.6
Hippocampus	tissue	29.2
Nucleus accumbens	tissue	28.7
Spinal cord	tissue	15.0
Choroid plexus	tissue	13.4
Retina	tissue	10.3
Corpus callosum	tissue	6.2
Adrenal gland	tissue	4.3
Gallbladder	tissue	2.3
Placenta	tissue	1.9
Stomach 1	tissue	1.8
Bone marrow	tissue	1.8
Thymus	tissue	1.5
Pituitary gland	tissue	1.4
Duodenum	tissue	1.1
Skin 1	tissue	1.0
Epididymis	tissue	0.8
Lung	tissue	0.8
Small intestine	tissue	0.8
Testis	tissue	0.7
Smooth muscle	tissue	0.7
Heart muscle	tissue	0.6
Colon	tissue	0.6
Salivary gland	tissue	0.5
Rectum	tissue	0.5
Tongue	tissue	0.5
Tonsil	tissue	0.5
Lymph node	tissue	0.4
Skeletal muscle	tissue	0.4
Endometrium 1	tissue	0.4
Thyroid gland	tissue	0.4

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Dorsal hippocampus (86.2), Transversal temporal gyrus, anterior (63.5), Ventral hippocampus (62.9), Postcentral gyrus, middle (62.1), Precentral gyrus, middle (62.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EPAS1, FOXO1, HIF1A, IKZF1

miRNA regulators (miRDB)

Targeting GABRG2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 145 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734

Functional genomics

gnomAD constraint: pLI 0.999, LOEUF 0.428, missense Z 3.93 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000639213 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈27% 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
5:162,068,000–162,093,911	73 / 72.2	1.01	no
5:162,093,912–162,103,956	104 / 209.3	0.50	no
5:162,103,957–162,149,271	42 / 156.9	0.27	yes (p 4.6e-20)
5:162,149,272–162,153,365	108 / 144.2	0.75	no
ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus (PMID:11748509)
• The GABRG2 gene seems to confer a rare, rather than frequent, major susceptibility effect to common idiopathic absence epilepsy syndromes. (PMID:12117362)
• modeling of molecular configuration (PMID:12225856)
• using full-length or truncated chimeric subunits it was demonstrated that homologous sequences from gamma2 are important for assembly of GABA(A) receptors composed of alpha(1), beta(3), and gamma(2) subunits (PMID:12367595)
• GABRG2 gene might be neither a susceptibility gene for CAE nor in linkage disequilibrium with disease-predisposing sites in the Chinese population (PMID:12384214)
• GABRG2 gene might be one of the susceptibility factors for febrile seizures (PMID:12672902)
• No difference in allele frequency observed for severe myoclonic epilepsy of infancy patients compared to control population. (PMID:12694927)
• In the polymorphic SNPs, significant differences between methamphetamine users and controls were identified in the female sample of the GABA(A)alpha1 subunit gene, and novel SNP in GABA(A)gamma2 subunit gene. No associations were found in the male sample. (PMID:14569258)
• Ser171 and Tyr172 in the GABAA receptor gamma2 subunit constitute a critical motif for access to the cell surface (PMID:14593118)
• Properties of recombinant GABRG2 receptor vary significantly from one expression system to another most likely due to differences in endogenous modulators. (PMID:14625018)
• serine 171 may play a critical role in the formation and stabilization of an exposed turn structure that is part of the subunit interaction site. (PMID:14736867)
• Association of the GABA(B)R1 with the GABA(A) receptor gamma2S subunit robustly promotes cell surface expression of GABA(B)R1 in the absence of GABA(B)R2, that is usually required for efficient trafficking of GABA(B)R1 to the cell surface. (PMID:14966130)
• Human gamma 2L subunit is capable of forming fully functional GABA receptors by itself in Xenopus oocytes. (PMID:14981251)
• Two etomidate sites allosterically enhance GABA(A) receptor subunit gating independently of agonist binding. (PMID:15016806)
• extracellular domain models show subunit arrangement of GABA-A receptors (PMID:15033447)
• Gaba A receptor gamma 1/3 immunolabeling in prefrontal cortex of bipolar disorder subjects was more intense than controls and schizophrenics. There was a significant increase in gamma 1 subunit in bipolar subjects, with no difference in schizophrenics. (PMID:15257153)
• the GABAA receptor mutation linked to human epilepsy (gamma2R43Q) impairs cell surface expression of alphabetagamma receptors (PMID:15342642)
• The GABAA receptor gamma2 subunit R43Q mutation impaired GABA(A) receptor function by compromising receptor trafficking and reducing surface expression. (PMID:15470132)
• Models of GABA(A) receptors composed of alpha1 beta3 gamma2 subunits were generated and were used for predicting putative engineered cross-link sites between the alpha1 and the gamma2 subunit. (PMID:16412095)
• a conserved lysine in the TM2-3 of alpha1, beta2, and gamma2 of the GABA-A receptor has an asymmetric function in different GABAA subunits (PMID:16627470)
• Our results suggest that common variants of strong effect in GABRG2 do not appear to play a role in the development of common, complex forms of epilepsy. (PMID:16806831)
• alpha4beta3gamma2L receptors have unique kinetic properties that limit the range of GABA applications to which they can respond maximally. (PMID:17124266)
• the gamma2 subunit of the GABA receptor gene might be one of the susceptibility factors for idiopathic generalized epilepsies (PMID:17162195)
• In south china, the K289M mutation and single-nucleotide polymorphism rs211014 of the GABRD2 gene not releate to children with febrile seizures. (PMID:17641256)
• study found mutations of GABRA1, GABRB3, and GABRG2 appear not to play a major role in the development of familial primary dystonia (PMID:17880575)
• This suggests that mutations in the GABRG2 gene is not a prevalent cause of familial cases of FS and epilepsy or GEFS+ in Scandinavia. (PMID:17927801)
• 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)
• Febrile Seizure is not related to the most common mutations of GABRG2 in two Tunisian families (PMID:18175077)
• built homology models of the ion pores of alpha1beta2 and alpha1beta2gamma2 GABA(A)-R using coordinates of the nicotinic acetylcholine receptor as a template to determine details about the zinc binding site (PMID:18197653)
• Using wild type/mutated receptor subunits to identify compounds with anesthetic effect. (PMID:18292428)
• Novel ligand-gated gamma aminobutyric acid receptor(GABRG)2 and sodium channel voltage-gated type I alpha subunit (SCN1A) gene mutations are found in two unrelated Chinese families with generalized epilepsy with febrile seizures plus (GEFS+). (PMID:18566737)
• Seizure susceptibility was significantly reduced in mice where the GABRG2 Q43 allele was suppressed during development. (PMID:18825662)
• results of the present study suggest that hippocampal neurons expressing GABAAgamma receptor subunits resist the progression of neurofibrillary degeneration in Alzheimer disease hippocampus (PMID:19019179)
• the mutation of the GABA(A)-receptor gamma 2 subunit gene (GABRG2) in a Chinese family with generalized epilepsy with febrile seizures plus (GEFS+ ) and the genotype-phenotype correlations and its inheritance (PMID:19065515)
• Our results support that SCN1A is the responsible gene for GEFS+ in one of the two studied Tunisian families and suggest a positive association of an intronic SNP in the GABRG2 gene in both families. (PMID:19236456)
• 2(L287A) mutation introduced a modest defect in GABA-induced gating that simultaneously increased propofol potentiation. (PMID:19553237)
• These findings suggest that in the autistic group this downregulation of both benzodiazepine sites and GABA(A) receptors in the ACC. (PMID:19650112)
• The results of the present study suggest that GABRG2 may be involved in SCZ susceptibility, but further studies are required. (PMID:19682861)
• Report interaction of androsterone and progesterone with inhibitory ligand-gated ion channels: a patch clamp study. (PMID:19705103)
• 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)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabrg2	ENSDARG00000053665
mus_musculus	Gabrg2	ENSMUSG00000020436
rattus_norvegicus	Gabrg2	ENSRNOG00000003241

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), 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:95623) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 48 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased susceptibility to pharmacologically induced seizures	3
abnormal inhibitory postsynaptic currents	3
postnatal lethality, complete penetrance	3
abnormal gait	2
seizures	2
absence seizures	2
abnormal GABA-mediated receptor currents	2
impaired behavioral response to xenobiotic	2
decreased bone mineral density	1
myoclonus	1
tremors	1
abnormal ovary morphology	1
abnormal testis morphology	1
enlarged testis	1
persistence of hyaloid vascular system	1
abnormal retina morphology	1
increased anxiety-related response	1
hyperactivity	1
decreased locomotor activity	1
impaired coordination	1
limb grasping	1
impaired righting response	1
reduced male fertility	1
abnormal skin morphology	1
premature death	1

+23 more (showing top 25).

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Macaca mulatta	D1LYT2	100.0%	Diamond
Drosophila melanogaster	P25123	99.8%	Diamond
Bos taurus	P57695	99.8%	Diamond
Macaca fascicularis	Q4R534	99.8%	Diamond
Pongo abelii	Q5RCC5	99.8%	Diamond
Drosophila simulans	Q9BLY8	99.8%	Diamond
Gallus gallus	P19150	96.9%	Diamond
Musca domestica	Q75NA5	84.3%	Diamond
Haemonchus contortus	P91730	81.4%	Diamond
Lymnaea stagnalis	P26714	58.6%	Diamond
Caenorhabditis elegans	O18276	57.3%	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
GABRA1-AS1	ncRNA	105377696
GABRA1	protein-coding	2554
LINC01202	ncRNA	104326188
GABRA6-AS1	ncRNA	132532400
GABRA6	protein-coding	2559

Protein

Protein identifiers

Gamma-aminobutyric acid receptor subunit gamma-2 — P18507 (reviewed: P18507)

Alternative names: GABA(A) receptor subunit gamma-2

All UniProt accessions (20): P18507, A0A1W2PP56, A0A1W2PPN5, A0A1W2PPS4, A0A1W2PQ81, A0A1W2PQA6, A0A1W2PQR9, A0A1W2PQX1, A0A1W2PR49, A0A1W2PRM8, A0A1W2PRN4, A0A1W2PRU1, A0A1W2PRY3, A0A1W2PSF4, A0A1X7SBS5, A0A1X7SBZ8, A0A286YFI6, A8MWU7, E5RGJ0, E5RIG3

UniProt curated annotations — full annotation on UniProt →

Function. Gamma 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. Gamma-2/GABRG2-containing GABAARs are found at both synaptic and extrasynaptic sites. Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission. GABAARs containing alpha-1 and beta-2 or -3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation. Extrasynaptic gamma-2-containing receptors contribute to the tonic GABAergic inhibition. GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response in a gamma-2 subunit-controlled manner.

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. Interacts with GABARAP. Interacts with KIF21B. Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3. Interacts with LHFPL4. Interacts with SHISA7; interaction leads to the regulation of GABA(A) receptor trafficking, channel deactivation kinetics and pharmacology.

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

Post-translational modifications. Palmitoylated by ZDHHC3/GODZ; required for the accumulation of GABA(A) receptors at the postsynaptic membrane of inhibitory GABAergic synapses.

Disease relevance. Developmental and epileptic encephalopathy 74 (DEE74) [MIM:618396] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE74 is an autosomal dominant form with onset in the first year of life. The gene represented in this entry is involved in disease pathogenesis. Epilepsy, childhood absence 2 (ECA2) [MIM:607681] A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Some individuals manifest febrile seizures. Absence seizures may either remit or persist into adulthood. Disease susceptibility is associated with variants affecting the gene represented in this entry. Febrile seizures, familial, 8 (FEB8) [MIM:607681] Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. The disease is caused by variants affecting the gene represented in this entry. Generalized epilepsy with febrile seizures plus 3 (GEFSP3) [MIM:607681] A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Allosterically activated by benzodiazepines. Activated by pentobarbital. Potentiated by etomidate, propofol, pregnanolone. Inhibited by the antagonist bicuculline. Inhibited by zinc ions. Potentiated by histamine.

Domain organisation. The extracellular domain contributes to synaptic contact formation. 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. GABRG2 sub-subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P18507-2	1	yes
P18507-1	2
P18507-3	3

RefSeq proteins (15): NP_000807, NP_001362268, NP_001362269, NP_001362270, NP_001362271, NP_001362272, NP_001362273, NP_001362274, NP_001362275, NP_001362276, NP_001362277, NP_001362278, NP_001362279, NP_944493, NP_944494* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005437	GABRG-1-4	Family
IPR005439	GABBAg2_rcpt	Family
IPR006028	GABAA/Glycine_rcpt	Family
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR018000	Neurotransmitter_ion_chnl_CS	Conserved_site
IPR036719	Neuro-gated_channel_TM_sf	Homologous_superfamily
IPR036734	Neur_chan_lig-bd_sf	Homologous_superfamily
IPR038050	Neuro_actylchol_rec	Homologous_superfamily

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea)

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

UniProt features (70 total): strand 16, sequence variant 13, helix 13, topological domain 5, sequence conflict 5, turn 5, transmembrane region 4, glycosylation site 3, splice variant 2, signal peptide 1, chain 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

showing 30 of 84 structures by resolution:

PDB	Title	Method	Resolution (Å)
9RGD	CryoEM structure of human alpha1beta3gamma2L GABA(A)R in CL47a	ELECTRON MICROSCOPY	2
8BHG	GABA-A receptor a5 heteromer - a5V2 - Bretazenil	X-RAY DIFFRACTION	2.39
9EQG	CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with GABA …	ELECTRON MICROSCOPY	2.4
9FAS	CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with …	ELECTRON MICROSCOPY	2.5
6X3T	Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus propofol	ELECTRON MICROSCOPY	2.55
8VRN	Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus PPTQ	ELECTRON MICROSCOPY	2.57
9FAJ	CryoEM structure of human full-length alpha1beta3gamma2 GABA(A) receptor in complex with …	ELECTRON MICROSCOPY	2.6
9FAK	CryoEM structure of human full-length alpha1beta3gamma2 GABA(A) receptor in complex with …	ELECTRON MICROSCOPY	2.6
9FGG	Cryo-EM structure of the full-length alpha1beta3gamma2 GABA(A) receptor in Saposin A …	ELECTRON MICROSCOPY	2.6
8SGO	Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus pregnenolone …	ELECTRON MICROSCOPY	2.65
7QNE	Cryo-EM structure of human full-length synaptic alpha1beta3gamma2 GABA(A)R in complex …	ELECTRON MICROSCOPY	2.7
9FG7	Cryo-EM structure of the full-length alpha1beta3gamma2 GABA(A) receptor in complex with …	ELECTRON MICROSCOPY	2.7
9FG9	Cryo-EM structure of the full-length alpha1beta3gamma2 GABA(A) receptor in complex with …	ELECTRON MICROSCOPY	2.7
9QJX	GABA-A receptor a2b3g2 + a2NB00(PAM) + GABA	ELECTRON MICROSCOPY	2.7
8SID	Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus …	ELECTRON MICROSCOPY	2.71
9QJY	GABA-A receptor a2b3g2 + a2NB04(silent) + GABA	ELECTRON MICROSCOPY	2.78
9FAP	CryoEM structure of human full-length alpha1beta3gamma2 GABA(A)R in complex with GARLH4 …	ELECTRON MICROSCOPY	2.8
9FFV	Cryo-EM structure of the alpha1beta3gamma2 GABA(A) receptor in complex with Nb38 in the …	ELECTRON MICROSCOPY	2.8
9TNS	GABA-A receptor a3b3g2 + GABA-PRE + a3NB83	ELECTRON MICROSCOPY	2.8
8VQY	Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus methaqualone	ELECTRON MICROSCOPY	2.82
6X40	Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus picrotoxin	ELECTRON MICROSCOPY	2.86
9TNB	GABA-A receptor a3b3g2 + a3NB77 + bicuculline	ELECTRON MICROSCOPY	2.87
8DD2	Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus Zolpidem	ELECTRON MICROSCOPY	2.9
8DD3	Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus DMCM	ELECTRON MICROSCOPY	2.9
9CRS	Native human GABAA receptor of beta2-alpha1-beta2-alpha1-gamma2 assembly	ELECTRON MICROSCOPY	2.9
9FAN	CryoEM structure of gamma2 subunit of GABA(A)R in complex with GARLH4, the TMD of …	ELECTRON MICROSCOPY	2.9
9FAQ	CryoEM structure of human full-length alpha1beta3gamma2 GABA(A)R in complex with GARLH4 …	ELECTRON MICROSCOPY	2.9
9FAR	CryoEM structure of gamma2 subunit of GABA(A)R in complex with GARLH4, the TMD of …	ELECTRON MICROSCOPY	2.9
9FAW	CryoEM structure of human full-length beta3gamma2 GABA(A) receptor in complex with …	ELECTRON MICROSCOPY	2.9
9FAX	CryoEM structure of human full-length beta3gamma2 GABA(A) receptor in complex with …	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18507-F1	77.41	0.59

Antibody-complex structures (SAbDab)

60 antibodies co-crystallized with this protein: 6D6T, 6D6U, 6HUG, 6HUJ, 6HUK, 6HUO, 6HUP, 6I53, 6X3S, 6X3T, 6X3U, 6X3V, 6X3W, 6X3X, 6X3Z, 6X40, 7QNA, 7QNB, 7QNE, 7T0W, 7T0Z, 8DD2, 8DD3, 8SGO, 8SI9 (+35 more)

Human Protein Atlas

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

Protein evidence: Evidence at protein level

Functional residue map

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

Disulfide bonds (1)

Type	Positions
Disulfide bond	190–204

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	52, 129, 247

Function

Pathways and Gene Ontology

Reactome pathways

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

7 pathways:

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

MSigDB gene sets: 465 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_274, GOBP_BEHAVIOR, GOBP_SYNAPSE_ASSEMBLY, LFA1_Q6, GOBP_ADULT_BEHAVIOR, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, TTGGGAG_MIR150, GOBP_CELL_CELL_SIGNALING, MODULE_66, PAX8_B, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (11): gamma-aminobutyric acid signaling pathway (GO:0007214), negative regulation of synaptic transmission, GABAergic (GO:0032229), synaptic transmission, GABAergic (GO:0051932), cellular response to histamine (GO:0071420), extrasynaptic signaling via GABA (GO:0160001), chloride transmembrane transport (GO:1902476), inhibitory synapse assembly (GO:1904862), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220), regulation of postsynaptic membrane potential (GO:0060078)

GO Molecular Function (9): GABA-A receptor activity (GO:0004890), chloride channel activity (GO:0005254), 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), protein binding (GO:0005515)

GO Cellular Component (15): plasma membrane (GO:0005886), axon (GO:0030424), cytoplasmic vesicle membrane (GO:0030659), dendrite membrane (GO:0032590), chloride channel complex (GO:0034707), dendritic spine (GO:0043197), postsynaptic membrane (GO:0045211), postsynapse (GO:0098794), GABA-ergic synapse (GO:0098982), postsynaptic specialization membrane (GO:0099634), GABA-A receptor complex (GO:1902711), membrane (GO:0016020), dendrite (GO:0030425), cytoplasmic vesicle (GO:0031410), synaptic membrane (GO:0097060)

Reactome top-level categories

5 top-level categories:

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

GO top-level categories

50 GO namespaces:

Category	Terms
synapse	3
GABA receptor activity	2
transmitter-gated monoatomic ion channel activity	2
neuron projection	2
dendrite	2
postsynapse	2
synaptic membrane	2
cellular anatomical structure	2
cell-cell signaling	1
regulation of synaptic transmission, GABAergic	1
negative regulation of synaptic transmission	1
synaptic transmission, GABAergic	1
chemical synaptic transmission	1
response to histamine	1
cellular response to nitrogen compound	1
gamma-aminobutyric acid signaling pathway	1
chloride transport	1
monoatomic anion transmembrane transport	1
synapse assembly	1
transport	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
regulation of membrane potential	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	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
binding	1
membrane	1
cell periphery	1
vesicle membrane	1
cytoplasmic vesicle	1
neuron projection membrane	1
monoatomic ion channel complex	1
neuron spine	1
postsynaptic membrane	1
postsynaptic specialization	1
GABA receptor complex	1
dendritic tree	1
cytoplasm	1
intracellular vesicle	1
plasma membrane region	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 35 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
chloride transmembrane transport	BP	direct assay
gamma-aminobutyric acid signaling pathway	BP	direct assay
inhibitory synapse assembly	BP	direct assay
synaptic transmission, GABAergic	BP	direct assay
dendritic spine	CC	direct assay
postsynaptic membrane	CC	direct assay
GABA-A receptor activity	MF	direct assay
GABA-gated chloride ion channel activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,638 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRG2	SCN1A	P35498	938
GABRG2	SCN1B	Q07699	935
GABRG2	CLCN2	P51788	889
GABRG2	SCN9A	Q15858	858
GABRG2	CACNA1H	O95180	727
GABRG2	SCN8A	Q9UQD0	703
GABRG2	SCN2A	Q99250	700
GABRG2	GPHN	Q9NQX3	665
GABRG2	PCDH19	Q8TAB3	663
GABRG2	SLC6A1	P30531	657
GABRG2	GAD1	Q99259	626
GABRG2	STXBP1	P61764	600
GABRG2	GAD2	Q05329	597
GABRG2	NOVA1	P51513	597
GABRG2	KCNQ2	O43526	593

IntAct

Human interaction partners of GABRG2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
GABRA1	physical association	0.550	2
GPAA1	association	0.530	1
NOVA1	physical association	0.400	2
CFTR	physical association	0.370	1
B4GALT5	association	0.350	1
GABRA4	physical association	0.320	1
GABRB3	physical association	0.320	1

BioGRID (35 interactions; top human partners by supporting records): GABARAP (Protein-peptide; 5 records), ABHD14A (Affinity Capture-MS; 2 records), BSCL2 (Affinity Capture-MS; 2 records), CANX (Affinity Capture-MS; 2 records), CPT1A (Affinity Capture-MS; 2 records), DNAJC18 (Affinity Capture-MS; 2 records), DRD5 (Affinity Capture-Western; 2 records), GABRG1 (Affinity Capture-MS; 2 records), GPAA1 (Affinity Capture-MS; 2 records), SHANK2 (Cross-Linking-MS (XL-MS); 2 records), TUBB1 (Affinity Capture-MS; 2 records), ATP13A1 (Affinity Capture-MS), B4GALT5 (Affinity Capture-MS), CFTR (PCA), DHRS7B (Cross-Linking-MS (XL-MS))

SIGNOR signaling

7 signaling interactions:

A	Effect	B	Mechanism
GABRG2	“form complex”	“GABA-A (a1-b1-g2) receptor”	binding
GABRG2	“form complex”	“GABA-A (a2-b1-g2) receptor”	binding
GABRG2	“form complex”	“GABA-A (a3-b1-g2) receptor”	binding
GABRG2	“form complex”	“GABA-A (a4-b1-g2) receptor”	binding
GABRG2	“form complex”	“GABA-A (a6-b1-g2) receptor”	binding
GABRG2	“form complex”	“GABA-A (a5-b1-g2) receptor”	binding
PRKCE	“down-regulates activity”	GABRG2	phosphorylation

Protein complexes (CORUM) (1)

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

1 complexes by size:

Complex	Subunits	Members
★ GABA-A receptor (GABRA1, GABRB2, GABRG2)	3	GABRA1, GABRB2, GABRG2

Ligand–receptor pairs (CellPhoneDB) (7)

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

7 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
GABRA6;GABRB3;GABRG2		Signaling by GABA
GABRA2;GABRB3;GABRG2		Signaling by GABA
GABRA1;GABRB2;GABRG2		Signaling by GABA
GABRA3;GABRB3;GABRG2		Signaling by GABA
GABRA1;GABRB3;GABRG2		Signaling by GABA
GABRA4;GABRB3;GABRG2		Signaling by GABA
GABRA5;GABRB3;GABRG2		Signaling by GABA

Disease & clinical

Genetic variants

Variant evidence for GABRG2: 821 ClinVar records (142 pathogenic / likely pathogenic); 10 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	82
Likely pathogenic	60
Uncertain significance	355
Likely benign	200
Benign	27

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 142 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
60708	NM_198904.4(GABRG2):c.968G>A (p.Arg323Gln)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
379114	NM_198904.4(GABRG2):c.269C>T (p.Thr90Met)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
503773	NM_198904.4(GABRG2):c.351dup (p.Ala118fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
205540	NM_198904.4(GABRG2):c.406C>T (p.Arg136Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
625863	NM_198904.4(GABRG2):c.844C>T (p.Pro282Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
205561	NM_198904.4(GABRG2):c.272T>G (p.Leu91Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
651395	NM_198904.4(GABRG2):c.501C>A (p.Asn167Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1508087	NM_198904.4(GABRG2):c.929C>T (p.Thr310Ile)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2507179	NM_198904.4(GABRG2):c.452_455del (p.Phe151fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3280411	NM_198904.4(GABRG2):c.892A>T (p.Lys298Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
408211	NM_198904.4(GABRG2):c.1061G>T (p.Gly354Val)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1017056	NM_198904.4(GABRG2):c.859G>A (p.Val287Ile)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
127233	NM_198904.4(GABRG2):c.247C>T (p.Pro83Ser)	Pathogenic	criteria provided, single submitter	2
205545	NM_198904.4(GABRG2):c.770-1G>A	Pathogenic	criteria provided, single submitter	1
205546	NM_198904.4(GABRG2):c.844C>A (p.Pro282Thr)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore GABRG2’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; 33 predictions of 710):

Position(s)	Effect	Δscore	Sites
5:162093826–162093827	acceptor_loss	1.0000	6
5:162093980	donor_loss	1.0000	3
5:162095492	acceptor_gain	1.0000
5:162095493–162095494	acceptor_loss	1.0000	6
5:162095563–162095564	donor_loss	1.0000	5
5:162101230	acceptor_gain	1.0000
5:162101233–162101234	acceptor_loss	1.0000	3
5:162101318–162101319	donor_loss	1.0000	5
5:162103883	acceptor_gain	1.0000
5:162103887–162103888	acceptor_loss	1.0000	2

AlphaMissense

1,848 missense substitutions predicted likely pathogenic (of 3,087 scored), across 361 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
M109	9	0.970	1.000
M315	9	0.958	0.999
M335	9	0.895	0.997
M199	9	0.879	0.996
D200	8	0.999	1.000
D336	8	0.999	1.000
D114	8	0.998	0.999
D123	8	0.998	1.000
D442	8	0.998	0.999
D149	8	0.997	1.000
H161	8	0.997	0.999
F294	8	0.996	1.000
F152	8	0.992	0.999
F266	8	0.988	0.999
N167	8	0.987	1.000
F345	8	0.987	0.998
F117	8	0.986	0.999
F449	8	0.986	0.999
D78	8	0.985	0.997
N154	8	0.984	0.999

HPA cancer prognostics

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

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	6.93e-05
Lung Adenocarcinoma (TCGA)	unfavorable	0.000718

Disease associations

OMIM: gene MIM:137164 | disease phenotypes: MIM:607681, MIM:611277, MIM:618396, MIM:600513, MIM:606369, MIM:600669, MIM:611136, MIM:117100

GenCC curated gene-disease

7 curated gene-disease records:

Disease	Classification	Inheritance	Records
epilepsy	Definitive	Autosomal dominant
febrile seizures, familial, 8	Strong	Autosomal dominant	4
developmental and epileptic encephalopathy, 74	Strong	Autosomal dominant	2
self-limited epilepsy with centrotemporal spikes	Supportive	Autosomal dominant
Dravet syndrome	Supportive	Autosomal dominant
generalized epilepsy with febrile seizures plus	Supportive	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
epilepsy	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 9 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
DDG2P	green
Early onset or syndromic epilepsy	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Paediatric disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Fetal anomalies	amber

Mondo (13): febrile seizures, familial, 8 (MONDO:0011891), developmental and epileptic encephalopathy, 74 (MONDO:0032725), sudden unexplained death in childhood (MONDO:1010117), familial sleep-related hypermotor epilepsy (MONDO:0000030), epilepsy (MONDO:0005027), Lennox-Gastaut syndrome (MONDO:0016532), intellectual disability (MONDO:0001071), idiopathic generalized epilepsy (MONDO:0005579), epilepsy, idiopathic generalized, susceptibility to, 13 (MONDO:0012627), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), (MONDO:0011794), generalized epilepsy with febrile seizures plus (MONDO:0018214), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (7): Genetic epilepsy with febrile seizure plus (Orphanet:36387), Childhood absence epilepsy (Orphanet:64280), Sleep-related hypermotor epilepsy (Orphanet:98784), Lennox-Gastaut syndrome (Orphanet:2382), Juvenile myoclonic epilepsy (Orphanet:307), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

showing 60 of 143 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000466	Limited neck range of motion
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000980	Pallor
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001266	Choreoathetosis
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001300	Parkinsonism
HP:0001315	Diminished deep tendon reflex
HP:0001326	EEG with irregular generalized spike and wave complexes
HP:0001327	Photosensitive myoclonic seizure
HP:0001328	Specific learning disability
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001508	Failure to thrive
HP:0001558	Decreased fetal movement
HP:0001763	Pes planus
HP:0002020	Gastroesophageal reflux
HP:0002059	Cerebral atrophy
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002076	Migraine
HP:0002121	Generalized non-motor (absence) seizure
HP:0002123	Generalized myoclonic seizure
HP:0002133	Status epilepticus
HP:0002188	Delayed CNS myelination
HP:0002197	Generalized-onset seizure
HP:0002283	Global brain atrophy
HP:0002307	Drooling
HP:0002311	Incoordination
HP:0002317	Unsteady gait

GWAS associations

10 associations:

Study	Trait	p-value
GCST003123_15	Severe influenza A (H1N1) infection	2e-13
GCST012490_615	Femur bone mineral density x serum urate levels interaction	2e-11
GCST004029_14	Angiotensin-converting enzyme inhibitor intolerance	8e-9
GCST012490_650	Femur bone mineral density x serum urate levels interaction	3e-8
GCST003075_52	Cognitive decline rate in late mild cognitive impairment	6e-7
GCST90000014_2	Parkinson’s disease motor subtype (tremor dominant vs postural instability/gait difficulty)	2e-6
GCST003265_284	Post bronchodilator FEV1/FVC ratio in COPD	3e-6
GCST011140_6	Glucagon levels in response to oral glucose tolerance test (decremental area under the curve for 0-30 minutes)	3e-6
GCST010105_146	Nicotine dependence symptom count	5e-6
GCST010105_53	Nicotine dependence symptom count	5e-6

EFO canonical traits (from GWAS)

7 canonical traits:

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:1001488	influenza A (H1N1)
EFO:0004713	FEV/FVC ratio
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0009262	nicotine dependence symptom count
EFO:0008463	glucagon measurement
EFO:0004531	urate measurement

MeSH disease descriptors

8 disease descriptors:

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065768	Lennox Gastaut Syndrome	C10.228.140.490.493.750; C16.320.495
C579932	Autosomal Dominant Nocturnal Frontal Lobe Epilepsy *(supp.)*
C567002	Epilepsy, Childhood Absence, Susceptibility To, 4 *(supp.)*
C562694	Epilepsy, Idiopathic Generalized *(supp.)*
C565811	Generalized Epilepsy With Febrile Seizures Plus, Type 3 *(supp.)*
C565808	Generalized Epilepsy with Febrile Seizures Plus *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (18): CHEMBL2093872 (PROTEIN COMPLEX GROUP), CHEMBL2094120 (PROTEIN COMPLEX), CHEMBL2094121 (PROTEIN COMPLEX), CHEMBL2094122 (PROTEIN COMPLEX), CHEMBL2094130 (PROTEIN COMPLEX), CHEMBL2095172 (PROTEIN COMPLEX), CHEMBL2095190 (PROTEIN COMPLEX), CHEMBL2109243 (PROTEIN COMPLEX GROUP), CHEMBL2111339 (PROTEIN COMPLEX), CHEMBL2111366 (PROTEIN COMPLEX)

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 GABRG2 — the drug acts on the assembly or class, not necessarily on this subunit alone.

2 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
ZALEPLON	GABA A receptor alpha-1/beta-1/gamma-2	3	4
ZOLPIDEM TARTRATE	GABA A receptor alpha-1/beta-1/gamma-2	3	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 613,620 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

55 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL661	ALPRAZOLAM	4	131,051
CHEMBL3183409	APALUTAMIDE	4	4,347
CHEMBL3187365	ASENAPINE	4	146
CHEMBL639	AZELASTINE	4	16,951
CHEMBL297302	BENPERIDOL	4	3,436
CHEMBL207538	BREXANOLONE	4	1,647
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,240
CHEMBL515	CHLORAMBUCIL	4	173,945
CHEMBL451	CHLORDIAZEPOXIDE	4	36,835
CHEMBL452	CLONAZEPAM	4	33,611
CHEMBL42	CLOZAPINE	4	37,868
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL12	DIAZEPAM	4	92,923
CHEMBL1082407	ENZALUTAMIDE	4	10,210
CHEMBL1106	EPINASTINE	4	8,600
CHEMBL1522	ESZOPICLONE	4	6,627
CHEMBL681	ETOMIDATE	4	8,520
CHEMBL407	FLUMAZENIL	4	7,208
CHEMBL13280	FLUNITRAZEPAM	4	11,627
CHEMBL1568698	GANAXOLONE	4	1,695
CHEMBL146095	GLAFENINE	4
CHEMBL15891	LINDANE	4
CHEMBL1544	LIOTHYRONINE	4
CHEMBL448	PENTOBARBITAL	4
CHEMBL526	PROPOFOL	4
CHEMBL1064	SIMVASTATIN	4
CHEMBL1983350	STIRIPENTOL	4
CHEMBL222559	TIPRANAVIR	4
CHEMBL646	TRIAZOLAM	4
CHEMBL408	TROGLITAZONE	4
CHEMBL1521	ZALEPLON	4
CHEMBL911	ZOLPIDEM	4
CHEMBL4105630	ZURANOLONE	4
CHEMBL312443	GABOXADOL	3
CHEMBL265502	SURAMIN	3
CHEMBL41632	TIRATRICOL	3
CHEMBL454095	ABECARNIL	2
CHEMBL190279	ALFAXALONE	2
CHEMBL1783282	AZD7325	2
CHEMBL8260	BAICALEIN	2
CHEMBL3681419	BASMISANIL	2
CHEMBL366947	BRETAZENIL	2
CHEMBL3647536	DARIGABAT	2
CHEMBL268254	DELORAZEPAM	2
CHEMBL275638	FLAVONE	2
CHEMBL1397886	LORECLEZOLE	2
CHEMBL200177	MK-0777	2
CHEMBL279867	PANADIPLON	2
CHEMBL43185	PIPERINE	2
CHEMBL287631	PROGABIDE	2
CHEMBL73416	SARIPIDEM	2
CHEMBL285802	ZOTEPINE	2
CHEMBL1783256	AZD6280	1
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1
CHEMBL273481	MUSCIMOL	1

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

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

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs77370934	Ace Inhibitors, Plain	Toxicity	Allele G is associated with increased likelihood of discontinuation when treated with Ace Inhibitors, Plain as compared to allele T.	PMID:28030426

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

Binding affinities (BindingDB)

1994 measured of 2157 human assays (2175 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
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
CHEMBL487686	KI	0.12 nM
CHEMBL469477	KI	0.12 nM
CHEMBL488283	KI	0.12 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
CHEMBL487687	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
6-[[3-(5-chloro-2-pyridinyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-N-(oxan-4-yl)pyridine-3-carboxamide	KI	0.2 nM	US-20240279218: ISOXAZOLYL ETHER DERIVATIVES AS GABA A ALPHA5 PAM
11-(4-Chloro-phenyl)-9-(4-methyl-thiazol-2-yl)-6,7-dihydro-5H-2,7a-diaza-dibenzo[a,c]cyclohepten-8-one	KI	0.2 nM
2’-Fluoro-5’-[8-fluoro-7-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridin-3-yl]-biphenyl-2-carbonitrile	KI	0.2 nM
3-(2,5-difluorophenyl)-7-(2-fluorophenyl)-2-((2-methyl-2H-1,2,4-triazol-3-yl)methoxy)pyrazolo[1,5-d][1,2,4]triazine	KI	0.2 nM
ethyl 3-fluoro-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepine-10-carboxylate	KI	0.2 nM
3-(3-fluoro-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepin-10-yl)-5-methyl-1,2,4-oxadiazole	KI	0.2 nM
CHEMBL566181	KI	0.2 nM
CHEMBL567243	KI	0.2 nM
CHEMBL571466	KI	0.2 nM
CHEMBL566189	KI	0.2 nM
2-(4-Bromo-phenyl)-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.21 nM
3’-(7-trifluoromethyl-imidazo[1,2-a]pyrimidin-3-yl)-biphenyl-2-carbonitrile	KI	0.21 nM
[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
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
4-(6-((1-(4-(Difluoromethyl)phenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methoxy)pyridazin-3-yl)-5,6-dihydropyridin-2(1H)-one	KI	0.27 nM	US-20250136581: SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
7-(2-fluorophenyl)-3-(3-fluorophenyl)-2-((2-methyl-2H-1,2,4-triazol-3-yl)methoxy)pyrazolo[1,5-d][1,2,4]triazine	KI	0.28 nM
8-Methoxy-5-methyl-6-oxo-5,6-dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid tert-butyl ester	KI	0.29 nM
2-(4-Fluoro-phenyl)-2,5,6,7,8,9-hexahydro-pyrazolo[4,3-c]quinolin-3-one	KI	0.29 nM
[3-(5-Cyclopropyl-[1,2,4]oxadiazol-3-yl)-4H-imidazo[1,5-a]quinoxalin-5-yl]-phenyl-methanone	KI	0.3 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

ChEMBL bioactivities

4309 potent at pChembl≥5 of 4573 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	Ki	0.02	nM	CHEMBL3144696
10.52	Ki	0.03	nM	CHEMBL3144849
10.40	Ki	0.04	nM	CHEMBL3144849
10.30	Ki	0.05	nM	PHENAZEPAM
10.30	Ki	0.05	nM	CGS-8216
10.30	Ki	0.05	nM	CHEMBL4243764
10.22	Ki	0.06	nM	PHENAZEPAM
10.22	Ki	0.06	nM	CHEMBL3144696
10.22	Ki	0.06	nM	CHEMBL4243764
10.15	Ki	0.07	nM	CHEMBL3144849
10.10	Ki	0.08	nM	CHEMBL3144696
10.10	Ki	0.08	nM	CGS-8216
10.10	Ki	0.08	nM	CHEMBL4243764
10.05	Ki	0.09	nM	CHEMBL3144841
10.00	IC50	0.1	nM	CHEMBL454349
10.00	Ki	0.1	nM	CHEMBL436768
10.00	Ki	0.1	nM	CHEMBL202696
10.00	Ki	0.1	nM	CHEMBL203286
10.00	Ki	0.1	nM	CHEMBL378761
10.00	Ki	0.1	nM	CHEMBL211704
10.00	Ki	0.1	nM	CHEMBL3144841
9.96	Ki	0.11	nM	CHEMBL380110
9.96	Ki	0.11	nM	CHEMBL3144841
9.92	Ki	0.12	nM	CHEMBL199957
9.92	Ki	0.12	nM	CHEMBL4476044
9.92	Ki	0.12	nM	CHEMBL487686
9.92	Ki	0.12	nM	CHEMBL488283
9.92	Ki	0.12	nM	CHEMBL469477
9.92	Ki	0.12	nM	PHENAZEPAM
9.92	Ki	0.12	nM	CHEMBL3144615
9.92	Ki	0.12	nM	CGS-8216
9.92	Ki	0.12	nM	CHEMBL4243764
9.85	Ki	0.14	nM	CHEMBL383677
9.85	Ki	0.14	nM	CHEMBL212008
9.85	Ki	0.14	nM	CHEMBL225631
9.85	Ki	0.14	nM	CHEMBL487687
9.85	Ki	0.14	nM	CHEMBL1644826
9.85	Ki	0.14	nM	CHEMBL130609
9.85	Ki	0.14	nM	CHEMBL10483
9.82	Ki	0.15	nM	CHEMBL202343
9.82	Ki	0.15	nM	CHEMBL206587
9.82	Ki	0.15	nM	CHEMBL3274851
9.82	Ki	0.15	nM	CHEMBL300615
9.80	IC50	0.16	nM	CHEMBL309517
9.80	Ki	0.16	nM	CHEMBL206380
9.77	Ki	0.17	nM	CHEMBL375742
9.77	Ki	0.17	nM	CHEMBL50763
9.77	Ki	0.17	nM	CHEMBL3144849
9.77	Ki	0.17	nM	CHEMBL3144615
9.77	Ki	0.17	nM	CHEMBL299210

PubChem BioAssay actives

2876 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-(4-ethynylphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	73089: Binding affinity to human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-2-beta-3-gamma-2	ki	<0.0001	uM
8-ethynyl-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73244: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-3-beta-3-gamma-2	ki	<0.0001	uM
1,4,5,6-tetrahydropyrimidine-5-carboxylic acid	1184360: Agonist activity at human GABAAalpha1beta2gamma2S receptor expressed in tsA-201cells by FLIPR membrane potential blue assay	ec50	<0.0001	uM
6-amino-2-methylpyridine-3-carboxylic acid	1184360: Agonist activity at human GABAAalpha1beta2gamma2S receptor expressed in tsA-201cells by FLIPR membrane potential blue assay	ec50	<0.0001	uM
8-methoxy-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	ki	0.0001	uM
2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	40988: Inhibition on Benzodiazepine receptor	ic50	0.0001	uM
5-fluoro-2-[2-fluoro-5-[7-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]benzonitrile	259132: Displacement of [3H]Ro-151788 from human recombinant GABAA alpha5 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0001	uM
8-chloro-2-phenyl-1H-pyrazolo[4,3-c]quinolin-3-one	73244: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-3-beta-3-gamma-2	ki	0.0001	uM
tert-butyl 8-hydroxy-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	ki	0.0001	uM
3-phenyl-6-(pyridazin-3-ylmethoxy)-[1,2,4]triazolo[3,4-a]phthalazine	72625: Binding affinity for human GABA-A receptor alpha-5-beta-3-gamma-2 subunits in L(tk-) cells	ki	0.0001	uM
2-[5-(7-ethyl-8-oxoimidazo[1,2-a]pyrazin-3-yl)-2-fluorophenyl]-5-fluorobenzonitrile	262297: Displacement of [3H]Ro-151788 from human recombinant GABA-Aalpha5 receptor plus beta3gamma2	ki	0.0001	uM
3,5-difluoro-2-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile	260334: Displacement of [3H]Ro 15-1788 from recombinant human GABAA alpha-1 receptor plus beta3gamma2 expressed in L(tk-) cells	ki	0.0001	uM
7-tert-butyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine	282667: Displacement of [3H]Ro 15-1788 from human recombinant GABAA alpha-3-beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
3-(2,6-difluorophenyl)-5-[4-fluoro-3-(3-fluoro-2-pyridinyl)phenyl]pyridazine	262644: Displacement of [3H]Ro-151788 from recombinant human GABA-Aalpha1 receptor plus beta3gamma2	ki	0.0001	uM
7-bromo-5-(2-fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one	1889907: Displacement of [3H]flunitrazepam from human recombinant alpha2beta2gamma2 GABAA receptor expressed in HEK cell membrane by competitive radioligand binding assay	ki	0.0001	uM
ethyl 6-methoxy-4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate	219791: Binding affinity measured using LtK- cell membranes expressing GABA alpha-1-beta-3-gamma-2 receptor	ki	0.0001	uM
2-(4-methylphenyl)-9-(2-thiophen-3-ylethyl)-6H-[1,2,4]triazolo[4,3-c]quinazoline-3,5-dione	552801: Displacement of [3H]flumazenil human recombinant alpha1beta3gamma2 GABA(A) receptor expressed in HEK293 cells after 30 mins by glass fiber filtration assay	ki	0.0001	uM
7-(2-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-thiophen-3-ylpyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
2-[3-[5-(2-hydroxypropan-2-yl)benzimidazol-1-yl]phenyl]benzonitrile	1604549: Displacement of [3H]-Ro15-1788 from human GABAA alpha5beta3gamma2 expressed in HEK293 cell membranes incubated for 40 or 90 mins by liquid scintillation counting method	ki	0.0001	uM
7-(2-fluorophenyl)-3-(furan-2-yl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]pyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
7-(2-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-thiophen-2-ylpyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0001	uM
2-[2-fluoro-5-[8-fluoro-7-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]benzonitrile	262219: Displacement of [3H]Ro 15-1788 from human GABA-Aalpha1 receptor plus beta-3-gamma-2 expressed in mouse L(tk-) cells	ki	0.0002	uM
8-chloro-2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	1388015: Displacement of [3H]Ro15-1788 from human GABAA receptor alpha1beta3gamma2 expressed in LTK cells preincubated for 30 secs measured every 15 mins at -60 mV holding potential by two-electrode voltage clamp assay	ki	0.0002	uM
[7-chloro-3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-4H-imidazo[1,5-a]quinoxalin-5-yl]-morpholin-4-ylmethanone	72905: Displacement of [3H]flunitrazepam from GABA-A receptor alpha-1-beta-2-gamma-2 subunits expressed in Sf9 cells	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
[3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-6-fluoro-4H-imidazo[1,5-a]quinoxalin-5-yl]-morpholin-4-ylmethanone	72906: Displacement of [3H]Flunitrazepam from GABA-A receptor alpha-1-beta-2-gamma-2 subunits expressed in Sf9 cells	ki	0.0002	uM
6-phenyl-9-[(2-propyl-1,2,4-triazol-3-yl)methoxy]-4,5,7,8-tetrazatetracyclo[9.2.2.02,10.03,7]pentadeca-2(10),3,5,8-tetraene	239566: Inhibition of [3H]Ro-151788 binding to recombinant human gamma-aminobutyric-acid A receptor alpha-5-beta-3-gamma-2 subtype expressed in L (tk-) cells	ki	0.0002	uM
9-[(1-benzylimidazol-2-yl)methoxy]-6-phenyl-4,5,7,8-tetrazatetracyclo[9.2.2.02,10.03,7]pentadeca-2(10),3,5,8-tetraene	239566: Inhibition of [3H]Ro-151788 binding to recombinant human gamma-aminobutyric-acid A receptor alpha-5-beta-3-gamma-2 subtype expressed in L (tk-) cells	ki	0.0002	uM
6-[(1-methylimidazol-2-yl)methoxy]-3-phenyl-[1,2,4]triazolo[3,4-a]phthalazine	72620: Binding affinity for human GABA-A receptor alpha-3-beta-3-gamma-2 subunits in L(tk-) cells	ki	0.0002	uM
9-[(3,5-dimethyl-2-pyridinyl)methoxy]-6-phenyl-4,5,7,8-tetrazatetracyclo[9.2.2.02,10.03,7]pentadeca-2(10),3,5,8-tetraene	239566: Inhibition of [3H]Ro-151788 binding to recombinant human gamma-aminobutyric-acid A receptor alpha-5-beta-3-gamma-2 subtype expressed in L (tk-) cells	ki	0.0002	uM
ethyl 15-methoxy-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carboxylate	448426: Binding affinity to GABAA alpha-5-beta-3-gamma-2 receptor	ki	0.0002	uM
ethyl 4-(methoxymethyl)-5-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate	1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assay	ic50	0.0002	uM
2-(4-chlorophenyl)-6,7,8,9-tetrahydro-1H-pyrazolo[4,3-c]quinolin-3-one	221780: In vitro binding affinity against gamma-aminobutyric acid A receptor, alpha 1 expressed in L(tk) cells by displacement of [3H]Ro-151788	ki	0.0002	uM
2-(4-bromophenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	ki	0.0002	uM
3-(2,5-difluorophenyl)-7-(2-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)methoxy]pyrazolo[1,5-d][1,2,4]triazine	267883: Inhibition of [3H]Ro15-1788 binding to human recombinant GABA-Aalpha3 plus beta-3-gamma-2 receptor expressed in L(tk-) cells	ki	0.0002	uM
3-(15-fluoro-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaen-5-yl)-5-methyl-1,2,4-oxadiazole	468635: Displacement of [3H]Flumazenil from cloned human GABA alpha-5-beta-3-gamma-2 receptor expressed in HEK293 cells	ki	0.0002	uM
ethyl 2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(17),3,5,9,11,13,15-heptaene-5-carboxylate	448426: Binding affinity to GABAA alpha-5-beta-3-gamma-2 receptor	ki	0.0002	uM
ethyl 15-chloro-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carboxylate	448426: Binding affinity to GABAA alpha-5-beta-3-gamma-2 receptor	ki	0.0002	uM
ethyl 15-fluoro-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carboxylate	468641: Displacement of [3H]Flumazenil from human GABA alpha-5-beta-3-gamma-2 receptor expressed in insect SF9 cells	ki	0.0002	uM
7-cyclobutyl-3-(2,6-difluorophenyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine	1604538: Displacement of [3H]-flumazenil from human GABAA alpha1beta3gamma2 expressed in Ltk cells	ki	0.0002	uM
Flumazenil	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	0.0002	uM
4-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]pyridine-3-carbonitrile	262147: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha5 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0003	uM
4-fluoro-2-[2-fluoro-5-[7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]benzonitrile	259132: Displacement of [3H]Ro-151788 from human recombinant GABAA alpha5 in combination with beta3gamma2 expressed in L(tk-) cells	ki	0.0003	uM
2-[3-(4-fluoro-3-pyridin-4-ylphenyl)imidazo[1,2-a]pyrimidin-7-yl]propan-2-ol	262147: Displacement of [3H]Ro 15-1788 from recombinant human GABA-Aalpha5 receptor plus beta-3-gamma-2 expressed in L(tk-) cells	ki	0.0003	uM
7-methoxy-2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one	72927: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-1-beta-3-gamma-2	ki	0.0003	uM
tert-butyl 8-azido-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	ki	0.0003	uM
ethyl (7S)-14-bromo-11-oxo-2,4,10-triazatetracyclo[10.4.0.02,6.07,10]hexadeca-1(16),3,5,12,14-pentaene-5-carboxylate	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	ki	0.0003	uM
tert-butyl 8-methoxy-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate	73523: Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor alpha-5-beta-3-gamma-2	ki	0.0003	uM
[3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-7-fluoro-4H-imidazo[1,5-a]quinoxalin-5-yl]-morpholin-4-ylmethanone	72906: Displacement of [3H]Flunitrazepam from GABA-A receptor alpha-1-beta-2-gamma-2 subunits expressed in Sf9 cells	ki	0.0003	uM
3-phenyl-6-(pyridin-4-ylmethoxy)-[1,2,4]triazolo[3,4-a]phthalazine	72625: Binding affinity for human GABA-A receptor alpha-5-beta-3-gamma-2 subunits in L(tk-) cells	ki	0.0003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
gamma-Aminobutyric Acid	affects binding, decreases reaction, increases activity, affects cotreatment, affects reaction (+1 more)	17
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Propofol	affects binding, decreases reaction, increases activity, increases reaction, affects reaction (+1 more)	4
1-(3-chlorophenyl)piperazine	decreases activity, increases reaction, affects cotreatment, affects reaction, increases activity (+2 more)	3
Hexachlorocyclohexane	increases activity, increases reaction, affects binding, decreases reaction	3
Diazepam	affects binding, increases activity, increases reaction, affects response to substance	3
2,4,2’,4’-tetrachlorobiphenyl	affects binding, increases activity, affects cotreatment, increases reaction, decreases reaction	2
tert-butylbicyclophosphorothionate	affects binding, decreases reaction	2
delta-hexachlorocyclohexane	affects cotreatment, increases activity, increases reaction, decreases reaction, decreases activity (+1 more)	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Flunitrazepam	affects binding, increases reaction, increases activity, affects reaction	2
Methamphetamine	increases response to substance, affects cotreatment, decreases reaction, increases activity	2
Pentobarbital	affects binding, decreases reaction, increases activity, increases reaction, affects cotreatment	2
Picrotoxin	affects binding, decreases reaction, increases activity	2
3,4-Methylenedioxyamphetamine	affects binding, decreases activity, increases reaction, affects cotreatment, affects reaction (+1 more)	2
6-methoxyflavone	affects binding, increases activity, increases reaction	1
6-methoxyflavanone	increases reaction, affects binding, increases activity	1
beta-thujone	affects binding, decreases reaction, increases activity	1
1-benzylpiperazine	decreases reaction, increases activity, affects binding	1
bisphenol A	increases methylation, affects cotreatment	1
carvone	affects binding, increases activity, increases reaction	1
2,5,2’,5’-tetrachlorobiphenyl	affects binding, affects cotreatment, increases activity	1
tetramethylenedisulfotetramine	affects binding, decreases reaction, increases activity, increases reaction	1
trichostatin A	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases activity, affects binding, decreases reaction	1
arsenite	increases methylation	1
bromoform	affects activity, affects binding	1
sodium arsenite	increases expression	1
1-(3-trifluoromethylphenyl)piperazine	affects binding, decreases reaction, increases activity	1
menthone	affects binding, increases activity, increases reaction	1

ChEMBL screening assays

1155 unique, capped per target: 940 binding, 201 functional, 10 admet, 4 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

14 cell lines: 7 transformed cell line, 3 cancer cell line, 3 spontaneously immortalized cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AY57	GM25431	Finite cell line	Female
CVCL_B8GM	Abcam HCT 116 GABRG2 KO	Cancer cell line	Male
CVCL_B8W7	Abcam MCF-7 GABRG2 KO	Cancer cell line	Female
CVCL_B9IV	Abcam A-549 GABRG2 KO	Cancer cell line	Male
CVCL_C0XQ	B’SYS CHO alpha1beta2gamma2 GABA(A)	Spontaneously immortalized cell line	Female
CVCL_C0YP	CHO-K1 GABA(A)R alpha1beta2gamma2L	Spontaneously immortalized cell line	Female
CVCL_C5TV	GABAA1-CHO	Spontaneously immortalized cell line	Female
CVCL_C9E7	B’SYS LTK alpha1beta2gamma2 GABA(A)	Transformed cell line	Male
CVCL_D1JK	PrecisION hGABAA alpha1/beta3/gamma2-HEK	Transformed cell line	Female
CVCL_D1JL	PrecisION hGABAA alpha3/beta3/gamma2-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

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

showing 60 of 372 trials:

NCT	Phase	Status	Title
NCT00004637	Phase 4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	Phase 4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	Phase 4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	Phase 4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	Phase 4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	Phase 4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	Phase 4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	Phase 4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	Phase 4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	Phase 4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	Phase 4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	Phase 4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	Phase 4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	Phase 4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	Phase 4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	Phase 4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	Phase 4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	Phase 4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	Phase 4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	Phase 4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	Phase 4	COMPLETED	RNS® System LTT Study
NCT00610532	Phase 4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	Phase 4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	Phase 4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	Phase 4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	Phase 4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	Phase 4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	Phase 4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	Phase 4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	Phase 4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	Phase 4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	Phase 4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	Phase 4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	Phase 4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	Phase 4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	Phase 4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	Phase 4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	Phase 4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	Phase 4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	Phase 4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy
NCT01309074	Phase 4	WITHDRAWN	Does Pregabalin Improve Symptoms of Anxiety in Patients With Epilepsy? A Comparison With Sertraline
NCT01318408	Phase 4	COMPLETED	Levetiracetam: The Anti-Convulsant of Choice for Elderly Patients With Dementia
NCT01498822	Phase 4	COMPLETED	Levetiracetam Versus Oxcarbazepine as Monotherapy to Evaluate Efficacy and Safety in Subjects With Newly or Recently Diagnosed Partial Epilepsy
NCT01546688	Phase 4	TERMINATED	A Study to Evaluate the Safety and Tolerability and Explore the Efficacy of Zonisamide as add-on Therapy in Elderly Patients With Refractory Partial Seizures
NCT01607346	Phase 4	TERMINATED	An Open Label Study to Evaluate the Effects of Ezogabine/Retigabine Added to Existing Anti-epileptic Drug(s) on Urinary Voiding Function in Subjects With Partial Onset Seizures
NCT01627860	Phase 4	COMPLETED	First Add-on vs. Mono-therapy Study of Topiramate in Neuro-Surgical Patients
NCT01689649	Phase 4	COMPLETED	A Study to Assess Tolerability and Efficacy of Topiramate Monotherapy in Recently Diagnosed Patients With Epilepsy
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Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for GABRG2 across ~30M SureChEMBL compounds — explore on Sugi Predict.