GABRE

Summary

GABRE (gamma-aminobutyric acid type A receptor subunit epsilon, HGNC:4085) is a protein-coding gene on chromosome Xq28, encoding Gamma-aminobutyric acid receptor subunit epsilon (P78334). Epsilon subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

The product of this gene belongs to the ligand-gated ionic channel (TC 1.A.9) family. It encodes the gamma-aminobutyric acid (GABA) A receptor which is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes an epsilon subunit. It is mapped to chromosome Xq28 in a cluster comprised of genes encoding alpha 3, beta 4 and theta subunits of the same receptor. Alternatively spliced transcript variants have been identified, but only one is thought to encode a protein.

Source: NCBI Gene 2564 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 148 total — 1 pathogenic
• GTEx eGene: eQTL in 18 tissues, sQTL in 25 (q < 0.05)
• ChEMBL bioactivity: 15 clinical-phase molecules tested; no curated mechanism-of-action drug
• MANE Select transcript: NM_004961
• Notable: 148 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4085
Approved symbol	GABRE
Name	gamma-aminobutyric acid type A receptor subunit epsilon
Location	Xq28
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000102287
Ensembl biotype	protein_coding
OMIM	300093
Entrez	2564

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 7 retained_intron, 4 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000370328

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 4, TSL 3: 3, TSL 4: 1, TSL 5: 1

ENST00000370328, ENST00000417300, ENST00000441219, ENST00000462018, ENST00000465405, ENST00000474932, ENST00000476016, ENST00000483564, ENST00000486255, ENST00000489333, ENST00000491339, ENST00000495862, ENST00000982121, ENST00000982122, ENST00000982123, ENST00001038158, ENST00001132546

RefSeq mRNA: 1 — MANE Select: NM_004961 NM_004961

CCDS: CCDS14703

Canonical transcript exons

ENST00000370328 — 9 exons

Exon	Start	End
ENSE00000677758	151961283	151961365
ENSE00001777377	151974570	151974676
ENSE00001918612	151953124	151955084
ENSE00003527722	151969669	151969736
ENSE00003529674	151959839	151959976
ENSE00003530319	151955708	151955860
ENSE00003537155	151970185	151970402
ENSE00003559432	151955368	151955567
ENSE00003685231	151962423	151962643

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 97.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.0722 / max 484.5433, expressed in 1203 samples.

Highest expression (Bgee): lower esophagus mucosa, omental fat pad, peritoneum, adipose tissue of abdominal region, vagina.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GABRE is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 25 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 43 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	sqtl	1.1e-43	+0.66	X:151957499:A:G
Nerve Tibial	sqtl	1.1e-38	+0.61	X:151957499:A:G
Thyroid	sqtl	3.5e-34	+0.54	X:151957499:A:G
Skin Sun Exposed Lower leg	eqtl	2.1e-24	-0.19	X:151973503:T:A
Cells Cultured fibroblasts	sqtl	1.1e-23	+0.46	X:151957499:A:G
Heart Left Ventricle	eqtl	7.8e-21	+0.43	X:152074191:G:A
Esophagus Mucosa	sqtl	3.9e-19	+0.38	X:151956439:G:C
Skin Sun Exposed Lower leg	sqtl	2.9e-18	+0.43	X:151965426:G:A
Adipose Visceral Omentum	sqtl	5.6e-18	+0.44	X:151956493:T:C
Skin Not Sun Exposed Suprapubic	sqtl	9.5e-16	-0.34	X:151956016:A:C
Artery Tibial	sqtl	1.1e-15	+0.37	X:151957499:A:G
Lung	sqtl	4.9e-14	+0.36	X:151957499:A:G
Skin Not Sun Exposed Suprapubic	eqtl	1.5e-13	-0.14	X:151973503:T:A
Breast Mammary Tissue	sqtl	5.3e-12	+0.43	X:151957499:A:G
Thyroid	eqtl	5.5e-10	-0.22	X:152253346:TA:T
Cells Cultured fibroblasts	eqtl	2.7e-09	-0.31	X:151870830:A:C
Minor Salivary Gland	eqtl	4.8e-08	+0.38	X:152041600:A:G
Artery Aorta	sqtl	1.8e-07	+0.38	X:151957499:A:G
Esophagus Muscularis	sqtl	9.4e-07	+0.31	X:151957499:A:G
Pancreas	sqtl	3.8e-06	+0.46	X:151957499:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
200840	12.0722	1203

Top tissues by expression

showing 100 of 287 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.36	gold quality
omental fat pad	UBERON:0010414	96.48	gold quality
peritoneum	UBERON:0002358	96.42	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.37	gold quality
vagina	UBERON:0000996	95.90	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.64	gold quality
apex of heart	UBERON:0002098	95.43	gold quality
adipose tissue	UBERON:0001013	95.21	gold quality
ectocervix	UBERON:0012249	95.19	gold quality
endocervix	UBERON:0000458	94.97	gold quality
skin of abdomen	UBERON:0001416	94.84	gold quality
esophagus mucosa	UBERON:0002469	94.47	gold quality
connective tissue	UBERON:0002384	93.69	gold quality
minor salivary gland	UBERON:0001830	92.18	gold quality
skin of leg	UBERON:0001511	92.13	gold quality
popliteal artery	UBERON:0002250	90.93	gold quality
tibial artery	UBERON:0007610	90.93	gold quality
left lobe of thyroid gland	UBERON:0001120	90.86	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.72	gold quality
right lung	UBERON:0002167	90.53	gold quality
right lobe of thyroid gland	UBERON:0001119	90.43	gold quality
uterine cervix	UBERON:0000002	90.25	gold quality
zone of skin	UBERON:0000014	89.97	gold quality
heart left ventricle	UBERON:0002084	89.96	gold quality
body of pancreas	UBERON:0001150	89.73	gold quality
body of uterus	UBERON:0009853	89.73	gold quality
left uterine tube	UBERON:0001303	89.71	gold quality
aorta	UBERON:0000947	89.45	gold quality
cardiac ventricle	UBERON:0002082	89.41	gold quality
stromal cell of endometrium	CL:0002255	89.21	gold quality
thyroid gland	UBERON:0002046	89.12	gold quality
mouth mucosa	UBERON:0003729	89.03	gold quality
upper lobe of left lung	UBERON:0008952	88.91	gold quality
esophagus	UBERON:0001043	88.68	gold quality
prostate gland	UBERON:0002367	88.41	gold quality
small intestine	UBERON:0002108	88.26	gold quality
placenta	UBERON:0001987	88.25	gold quality
gall bladder	UBERON:0002110	88.01	gold quality
ascending aorta	UBERON:0001496	87.96	gold quality
thoracic aorta	UBERON:0001515	87.80	gold quality
tibial nerve	UBERON:0001323	87.76	gold quality
colonic epithelium	UBERON:0000397	87.72	gold quality
descending thoracic aorta	UBERON:0002345	87.59	gold quality
heart	UBERON:0000948	86.46	gold quality
upper lobe of lung	UBERON:0008948	86.37	gold quality
right atrium auricular region	UBERON:0006631	86.10	gold quality
mucosa of stomach	UBERON:0001199	85.94	gold quality
transverse colon	UBERON:0001157	85.83	gold quality
saliva-secreting gland	UBERON:0001044	85.27	gold quality
left coronary artery	UBERON:0001626	85.17	gold quality
metanephros cortex	UBERON:0010533	85.13	gold quality
rectum	UBERON:0001052	84.70	gold quality
cardiac atrium	UBERON:0002081	84.63	gold quality
upper leg skin	UBERON:0004262	84.59	gold quality
coronary artery	UBERON:0001621	84.50	gold quality
urinary bladder	UBERON:0001255	84.16	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.09	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.62	gold quality
left ovary	UBERON:0002119	83.10	gold quality
mucosa of transverse colon	UBERON:0004991	83.07	gold quality
female reproductive system	UBERON:0000474	83.04	gold quality
left adrenal gland cortex	UBERON:0035825	82.40	gold quality
mammalian vulva	UBERON:0000997	82.38	gold quality
spleen	UBERON:0002106	82.25	gold quality
skin of hip	UBERON:0001554	82.23	gold quality
right ovary	UBERON:0002118	82.19	gold quality
lower esophagus	UBERON:0013473	82.08	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.04	gold quality
pharyngeal mucosa	UBERON:0000355	82.03	gold quality
adenohypophysis	UBERON:0002196	82.00	gold quality
cervix epithelium	UBERON:0004801	81.81	gold quality
intestine	UBERON:0000160	81.74	gold quality
pancreas	UBERON:0001264	81.53	gold quality
sural nerve	UBERON:0015488	81.07	gold quality
left adrenal gland	UBERON:0001234	80.87	gold quality
right coronary artery	UBERON:0001625	80.63	gold quality
right uterine tube	UBERON:0001302	80.55	gold quality
urethra	UBERON:0000057	80.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	80.25	gold quality
uterus	UBERON:0000995	80.17	gold quality
duodenum	UBERON:0002114	80.13	gold quality
colon	UBERON:0001155	80.09	gold quality
adrenal cortex	UBERON:0001235	80.05	gold quality
right adrenal gland cortex	UBERON:0035827	79.99	gold quality
right adrenal gland	UBERON:0001233	79.88	gold quality
jejunal mucosa	UBERON:0000399	79.84	gold quality
large intestine	UBERON:0000059	79.67	gold quality
upper arm skin	UBERON:0004263	79.46	gold quality
calcaneal tendon	UBERON:0003701	79.38	gold quality
myometrium	UBERON:0001296	79.23	gold quality
body of stomach	UBERON:0001161	78.75	gold quality
fallopian tube	UBERON:0003889	78.65	gold quality
oviduct epithelium	UBERON:0004804	78.54	gold quality
ovary	UBERON:0000992	78.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.16	gold quality
hypothalamus	UBERON:0001898	77.82	gold quality
right lobe of liver	UBERON:0001114	77.69	gold quality
sigmoid colon	UBERON:0001159	77.64	gold quality
adrenal gland	UBERON:0002369	77.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.29	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.94
E-CURD-11	no	187.48

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 66 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Locus coeruleus	tissue	74.0
Hypothalamus	tissue	45.2
Septum	tissue	24.9
Amygdala	tissue	13.4
Pons	tissue	12.7
Substantia nigra	tissue	11.6
Periaqueductal gray	tissue	11.0
Adipose tissue	tissue	9.1
Heart muscle	tissue	8.9
Hippocampal formation	tissue	8.6
Medulla oblongata	tissue	3.7
Seminal vesicle	tissue	3.2
Placenta	tissue	3.1
Skin 1	tissue	3.0
Ventral forebrain	tissue	3.0
Choroid plexus	tissue	2.9
Midbrain	tissue	2.7
Vagina	tissue	2.2
Pituitary gland	tissue	2.1
Epididymis	tissue	1.7
Spinal cord	tissue	1.5
Cervix	tissue	1.2
Breast	tissue	0.9
Nucleus accumbens	tissue	0.9
Salivary gland	tissue	0.8
Parathyroid gland	tissue	0.8
Esophagus	tissue	0.7
Pancreas	tissue	0.7
Basal ganglia	tissue	0.7
Prostate	tissue	0.7
Postcentral gyrus	tissue	0.7
Duodenum	tissue	0.6
Fallopian tube	tissue	0.6
Endometrium 1	tissue	0.5
Putamen	tissue	0.5
Superior colliculi	tissue	0.5
Lung	tissue	0.5
Gallbladder	tissue	0.5
Hippocampus	tissue	0.5
Prefrontal cortex	tissue	0.4
Cerebral cortex	tissue	0.4
Colon	tissue	0.4
Adrenal gland	tissue	0.4
Retrosplenial and cingulate cortex	tissue	0.4
Ovary	tissue	0.3
Rectum	tissue	0.3
Skeletal muscle	tissue	0.3
Smooth muscle	tissue	0.3
Urinary bladder	tissue	0.3
Thyroid gland	tissue	0.3
Olfactory bulb	tissue	0.3
Caudate putamen	tissue	0.3
Appendix	tissue	0.3
Temporal cortex	tissue	0.3
Insular cortex	tissue	0.3
Lymph node	tissue	0.2
Motor cortex	tissue	0.2
Thalamus	tissue	0.2
Kidney	tissue	0.2
Tonsil	tissue	0.2

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Arcuate nucleus (103.9), Median raphe nucleus (81.8), Dorsal raphe nucleus (38.0), Piriform cortex (33.2), Ventromedial nucleus (29.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

showing 30 of 79 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4251	99.40	69.19	3363

Functional genomics

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000370328 — one region, missense o/e 1.02.

Literature-anchored findings (GeneRIF, showing 14)

• Analysis of epilepsy inter-patient variability of eleven highly expressed GABAAR subunit mRNAs found seven of the subunits varied between patients, as did whole cell GABAAR currents. (PMID:15755675)
• We report here that the GABA-activated current can be potentiated at pH 8.4 for both alphabeta and alphabeta gamma subunit-containing receptors, but only at GABA concentrations below the EC40. (PMID:15946973)
• We infer that activation by anesthetics and GABA induces a similar conformational change at the M2 segment 6’ position that is related to channel opening. (PMID:17293408)
• Increased intracortical excitability is noted in subjects affected by the GABA A receptor gamma 2 subunit (GABRG2 Arg43Glu) mutation; findings are likely to represent an important clue to mechanisms linking this gene defect and the epilepsy phenotype. (PMID:17615250)
• Increased expression of epsilon, in conjunction with alpha2 and beta3 subunits, results in expression of GABAA receptors with correspondingly altered rectification, deactivation and levels of spontaneous openings, but not increased total current density. (PMID:17714454)
• Although GABRE genes did not show positive association, further studies are necessary to consider the role of other GABA receptor genes in migraine susceptibility (PMID:19087248)
• Using published alpha subunit data we identified two principal components labeled ‘Decreasing’ (alpha2, alpha5, beta1, gamma1 and gamma3) and ‘Dynamic’ (alpha1, alpha4, beta2 and gamma2) responsible for 84% of variation in GABA(A)R subunit development. (PMID:20609421)
• single nucleotide polymorphisms studied in the GABRA4, GABRE, and GABRQ genes are not related to the risk for familial ET. (PMID:21422964)
• GABRE protein levels were significantly increased in schizophrenia, major depressive disorder, and bipolar disorder patients’ lateral cerebellum compared to controls. (PMID:24022508)
• Data indicate that GABA(A) receptor subunit epsilon (GABRE) approximately miR-452 approximately miR-224 locus is downregulated and hypermethylated in prostate cancer and is a promising epigenetic candidate biomarker for prostate cancer diagnosis and prognosis. (PMID:24737792)
• This study showed that in male groups, the expression of GABRE was generally lower in schizophrenia cases compared to the control. (PMID:25660468)
• data from the present study suggest a marginal role of GABRE rs1139916 in the risk for migraine in women. (PMID:29299688)
• Comprehensive Transcriptome Profiling of Cryptic CBFA2T3-GLIS2 Fusion-Positive AML Defines Novel Therapeutic Options: A COG and TARGET Pediatric AML Study. (PMID:31719049)
• Rare variants in the GABAA receptor subunit epsilon identified in patients with a wide spectrum of epileptic phenotypes. (PMID:32588540)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gabre	ENSMUSG00000031340
rattus_norvegicus	Gabre	ENSRNOG00000061182

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090), GABRA5 (ENSG00000186297), ZACN (ENSG00000186919), GABRD (ENSG00000187730), CHRNG (ENSG00000196811), GABRQ (ENSG00000268089)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1330235) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
reduced fertility	1
impaired behavioral response to anesthetic	1
prolonged RR interval	1

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Macaca mulatta	D1LYT2	100.0%	Diamond
Macaca fascicularis	Q4R534	99.8%	Diamond
Pongo abelii	Q5RCC5	99.8%	Diamond
Bos taurus	P08219	99.3%	Diamond
Gallus gallus	P19150	96.9%	Diamond
Haemonchus contortus	P91730	81.4%	Diamond
Lymnaea stagnalis	P26714	58.6%	Diamond
Caenorhabditis elegans	O18276	57.3%	Diamond
Drosophila melanogaster	Q24352	41.2%	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
MIR224	ncRNA	407009
MAGEA10	protein-coding	4109
MIR452	ncRNA	574412
GABRA3	protein-coding	2556
MIR105-1	ncRNA	406897
CNGA2	protein-coding	1260
MAGEA4	protein-coding	4103
FATE1	protein-coding	89885
MAGEA4-AS1	ncRNA	105373368

Protein

Protein identifiers

Gamma-aminobutyric acid receptor subunit epsilon — P78334 (reviewed: P78334)

Alternative names: GABA(A) receptor subunit epsilon

All UniProt accessions (2): P78334, F2Z2H5

UniProt curated annotations — full annotation on UniProt →

Function. Epsilon 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 interfaces. When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. GABAARs containing epsilon subunits also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings. GABARs containing epsilon subunit may regulate cardiac function.

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 many tissues. Highest levels of expression in adult heart and placenta.

Activity regulation. Potentiated by pentobarbital, loreclezole, and lanthanum and inhibited by zinc and furosemide. Introduction of the epsilon subunit to the receptor complex resulted in diminished modulatory effects by etomidate, propofol, pregnanolone and flurazepam.

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

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

Isoforms (2)

UniProt ID	Names	Canonical?
P78334-1	1	yes
P78334-2	2

RefSeq proteins (1): NP_004952* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006028	GABAA/Glycine_rcpt	Family
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR008099	GABAAe_rcpt	Family
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 (23 total): sequence conflict 4, topological domain 4, transmembrane region 4, region of interest 2, glycosylation site 2, splice variant 2, sequence variant 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78334-F1	73.13	0.40

Human Protein Atlas

Protein class: Predicted membrane proteins, FDA approved drug targets, Small molecule drugs, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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	195–209

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	134, 252

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 159 (showing top): MODULE_274, GOBP_SYNAPSE_ASSEMBLY, JAEGER_METASTASIS_DN, PEREZ_TP63_TARGETS, MODULE_64, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_CELL_CELL_SIGNALING, NFKB_Q6, PATIL_LIVER_CANCER, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_CHLORIDE_TRANSPORT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4

GO Biological Process (8): gamma-aminobutyric acid signaling pathway (GO:0007214), synaptic transmission, GABAergic (GO:0051932), chloride transmembrane transport (GO:1902476), inhibitory synapse assembly (GO:1904862), negative regulation of chloride transport (GO:2001226), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (7): GABA-A receptor activity (GO:0004890), GABA-gated chloride ion channel activity (GO:0022851), 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), transmitter-gated monoatomic ion channel activity (GO:0022824)

GO Cellular Component (7): dendrite membrane (GO:0032590), chloride channel complex (GO:0034707), postsynaptic membrane (GO:0045211), postsynapse (GO:0098794), GABA-A receptor complex (GO:1902711), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

34 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of chloride transport	BP	direct assay
GABA-A receptor complex	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 902 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRE	UBL4A	P11441	610
GABRE	F8	P00451	499
GABRE	GABBR2	O75899	473
GABRE	TMTC2	Q8N394	440
GABRE	GRPR	P30550	434
GABRE	L1CAM	P32004	429
GABRE	HCFC1	P51610	427
GABRE	SYN1	P17600	403
GABRE	SEMA4G	Q9NTN9	402
GABRE	SYP	P08247	388
GABRE	NTNG2	Q96CW9	388
GABRE	NTNG1	Q9Y2I2	385
GABRE	GPM6B	Q13491	384
GABRE	TH	P07101	384
GABRE	HPRT1	P00492	383

IntAct

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

3 partners by confidence:

Partner	Interaction type	MIscore	Records
FZD6	association	0.530	2
HSPE1	physical association	0.400	1
B4GAT1	association	0.350	1

BioGRID (92 interactions; top human partners by supporting records): ALG9 (Affinity Capture-MS; 3 records), BSCL2 (Affinity Capture-MS; 3 records), CCPG1 (Affinity Capture-MS; 3 records), ENTPD4 (Affinity Capture-MS; 3 records), EPHB4 (Affinity Capture-MS; 3 records), ERMP1 (Affinity Capture-MS; 3 records), FADS1 (Affinity Capture-MS; 3 records), FZD6 (Affinity Capture-MS; 3 records), GP1BB (Affinity Capture-MS; 3 records), GRAMD1A (Affinity Capture-MS; 3 records), HMBS (Affinity Capture-MS; 3 records), KCNQ5 (Affinity Capture-MS; 3 records), LMF2 (Affinity Capture-MS; 3 records), MIA3 (Affinity Capture-MS; 3 records), SGPP1 (Affinity Capture-MS; 3 records)

Protein complexes (CORUM) (2)

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

2 complexes by size:

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

Ligand–receptor pairs (CellPhoneDB) (1)

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

1 ligand–receptor pairs:

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

Disease & clinical

Genetic variants

Variant evidence for GABRE: 148 ClinVar records (1 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	75
Likely benign	13
Benign	5

Top pathogenic / likely-pathogenic (1)

Showing all 1 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
599549	NM_004961.4(GABRE):c.399C>A (p.Tyr133Ter)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore GABRE’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; 41 predictions of 1,129):

Position(s)	Effect	Δscore	Sites
X:151955706–151955707	donor_loss	1.0000	5
X:151955861	acceptor_loss	1.0000	2
X:151962421–151962422	donor_loss	1.0000	5
X:151962644–151962645	acceptor_loss	1.0000	6
X:151974569	donor_loss	1.0000
X:151955360	donor_gain	0.9900
X:151955568–151955569	acceptor_loss	0.9900	6
X:151955862	acceptor_loss	0.9900	3
X:151959837–151959838	donor_loss	0.9900	6
X:151959977–151959978	acceptor_loss	0.9900	6

AlphaMissense

880 missense substitutions predicted likely pathogenic (of 3,352 scored), across 238 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
D205	8	0.983	0.994
D128	8	0.973	0.988
D341	8	0.940	0.974
F299	8	0.932	0.988
D154	8	0.928	0.977
D119	8	0.919	0.962
F157	8	0.899	0.983
D481	8	0.893	0.949
S215	8	0.870	0.998
F271	8	0.868	0.983
F488	8	0.862	0.960
F213	8	0.844	0.987
H207	8	0.828	0.935
W151	7	0.991	0.998
C195	7	0.991	0.996
W126	7	0.988	0.997
C209	7	0.985	0.995
F202	7	0.978	0.994
F245	7	0.977	0.994
R275	7	0.959	0.992

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000112
Breast Invasive Carcinoma (validation)	favorable	0.000281

Disease associations

OMIM: gene MIM:300093 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2093872 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 447,242 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

15 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3183409	APALUTAMIDE	4	4,347
CHEMBL207538	BREXANOLONE	4	1,647
CHEMBL452	CLONAZEPAM	4	33,611
CHEMBL12	DIAZEPAM	4	92,923
CHEMBL1082407	ENZALUTAMIDE	4	10,210
CHEMBL407	FLUMAZENIL	4	7,208
CHEMBL1568698	GANAXOLONE	4	1,695
CHEMBL1544	LIOTHYRONINE	4	23,991
CHEMBL454095	ABECARNIL	2	566
CHEMBL8260	BAICALEIN	2	8,718
CHEMBL268254	DELORAZEPAM	2	1,315
CHEMBL275638	FLAVONE	2	89,655
CHEMBL287631	PROGABIDE	2	3,882
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1	161,661
CHEMBL273481	MUSCIMOL	1	5,813

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

ChEMBL bioactivities

474 potent at pChembl≥5 of 511 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
9.05	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	IC50	2	nM	MUSCIMOL
8.66	IC50	2.2	nM	CHEMBL80610
8.64	IC50	2.3	nM	FIPRONIL
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
8.40	IC50	3.981	nM	CHEMBL301605
8.40	Ki	4	nM	CHEMBL330116
8.40	Ki	4	nM	CHEMBL3407528

PubChem BioAssay actives

409 with measured affinity, of 877 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
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
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
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
1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole	242615: In vitro insecticidal activity as inhibition of [3H]EBOB binding to Gamma-aminobutyric acid GABA-A receptor of housefly neuronal membranes	ic50	0.0042	uM
2-amino-N-[4-chloro-2-(2-chlorobenzoyl)phenyl]acetamide	40974: In vitro displacement of [3H]-diazepam from GABA-A Benzodiazepine receptor	ic50	0.0048	uM
3-(7-fluoro-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	0.0050	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
Air Pollutants	decreases expression, increases abundance, increases expression	3
Estradiol	increases expression, affects cotreatment, decreases expression	3
Aflatoxin B1	decreases methylation, increases expression, increases methylation	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol A	affects expression, affects cotreatment, increases methylation	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Dexamethasone	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
cupric chloride	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	decreases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Azathioprine	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Etomidate	increases reaction, affects binding, increases activity	1

ChEMBL screening assays

185 unique, capped per target: 166 binding, 15 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 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1SJ	Abcam HeLa GABRE KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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