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): 147 total — 1 pathogenic
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004961

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: 12 — 7 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000370328, ENST00000417300, ENST00000441219, ENST00000462018, ENST00000465405, ENST00000474932, ENST00000476016, ENST00000483564, ENST00000486255, ENST00000489333, ENST00000491339, ENST00000495862

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.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200840	12.0722	1203

Top tissues by expression

287 total, 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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-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

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)

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), 1 shown:

• 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

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

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

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): 195–209

Glycosylation sites (2): 134, 252

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

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 (8): 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), benzodiazepine receptor activity (GO:0008503), transmitter-gated monoatomic ion channel activity (GO:0022824)

GO Cellular Component (8): 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), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

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
neurotransmitter receptor 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
cell junction	1

Protein interactions and networks

STRING

708 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRE	UBL4A	P11441	602
GABRE	GAD1	Q99259	522
GABRE	F8	P00451	496
GABRE	GABBR2	O75899	487
GABRE	L1CAM	P32004	439
GABRE	HCFC1	P51610	427
GABRE	GRPR	P30550	424
GABRE	TMEM200A	Q86VY9	419
GABRE	SYP	P08247	395
GABRE	SYN1	P17600	392
GABRE	GPM6B	Q13491	392
GABRE	HPRT1	P00492	387
GABRE	GDI1	P31150	387
GABRE	NTNG2	Q96CW9	387
GABRE	NTNG1	Q9Y2I2	382

IntAct

5 interactions, top by confidence:

A	B	Type	Score
GABRE	FZD6	psi-mi:“MI:0914”(association)	0.530
GABRE	HSPE1	psi-mi:“MI:0915”(physical association)	0.400
GABRE	B4GAT1	psi-mi:“MI:0914”(association)	0.350

BioGRID (92): SEC11A (Affinity Capture-MS), LSR (Affinity Capture-MS), HLA-A (Affinity Capture-MS), PIGO (Affinity Capture-MS), ALG9 (Affinity Capture-MS), GPAA1 (Affinity Capture-MS), SLC4A2 (Affinity Capture-MS), TMTC3 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), MIA3 (Affinity Capture-MS), HMBS (Affinity Capture-MS), STIM1 (Affinity Capture-MS), TTC17 (Affinity Capture-MS), SPCS2 (Affinity Capture-MS), POMT1 (Affinity Capture-MS)

ESM2 similar proteins: A2A259, A5X5Y0, H2Q5A1, O46547, O70212, O95264, O97741, P01906, P01909, P02713, P02715, P02716, P04758, P04759, P04760, P07510, P09660, P09690, P11230, P13536, P18916, P20782, P23979, P25109, P25110, P35563, P37088, P37089, P46098, P55270, P78334, Q04844, Q07001, Q14246, Q5Y4N8, Q60HE8, Q61180, Q61549, Q70Z44, Q7Z418

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	74
Likely benign	13
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
599549	NM_004961.4(GABRE):c.399C>A (p.Tyr133Ter)	Pathogenic

SpliceAI

2020 predictions. Top by Δscore:

Variant	Effect	Δscore
X:151955565:TCC:T	acceptor_gain	1.0000
X:151955566:CCC:C	acceptor_gain	1.0000
X:151955858:CAC:C	acceptor_gain	1.0000
X:151955859:AC:A	acceptor_gain	1.0000
X:151955860:CC:C	acceptor_gain	1.0000
X:151955861:C:CC	acceptor_gain	1.0000
X:151955861:CTGAA:C	acceptor_loss	1.0000
X:151959838:CCAA:C	donor_gain	1.0000
X:151959874:A:AC	donor_gain	1.0000
X:151959874:ACT:A	donor_gain	1.0000
X:151959875:C:CC	donor_gain	1.0000
X:151959875:CTC:C	donor_gain	1.0000
X:151959977:C:CC	acceptor_gain	1.0000
X:151962419:ATACC:A	donor_loss	1.0000
X:151962420:TACCT:T	donor_loss	1.0000
X:151962421:A:C	donor_loss	1.0000
X:151962422:C:CT	donor_loss	1.0000
X:151962447:T:TA	donor_gain	1.0000
X:151962640:ATTC:A	acceptor_gain	1.0000
X:151962641:TTC:T	acceptor_gain	1.0000
X:151962642:TC:T	acceptor_gain	1.0000
X:151962643:CCTGG:C	acceptor_gain	1.0000
X:151962644:C:CC	acceptor_gain	1.0000
X:151962644:CTG:C	acceptor_loss	1.0000
X:151962645:T:C	acceptor_loss	1.0000
X:151974565:CTCA:C	donor_loss	1.0000
X:151974566:TCAC:T	donor_loss	1.0000
X:151974567:CACCT:C	donor_loss	1.0000
X:151974569:C:CT	donor_loss	1.0000
X:151955080:CGAGG:C	acceptor_gain	0.9900

AlphaMissense

3352 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:151961284:G:C	S215R	0.998
X:151961284:G:T	S215R	0.998
X:151961286:T:G	S215R	0.998
X:151962535:A:G	W151R	0.998
X:151962535:A:T	W151R	0.998
X:151962610:A:G	W126R	0.997
X:151962610:A:T	W126R	0.997
X:151961297:A:G	L211P	0.996
X:151961345:C:G	C195S	0.996
X:151961346:A:G	C195R	0.996
X:151961346:A:T	C195S	0.996
X:151962533:C:A	W151C	0.996
X:151962533:C:G	W151C	0.996
X:151961304:A:G	C209R	0.995
X:151962608:C:A	W126C	0.995
X:151962608:C:G	W126C	0.995
X:151959888:A:C	F245L	0.994
X:151959888:A:T	F245L	0.994
X:151959890:A:G	F245L	0.994
X:151961316:C:G	D205H	0.994
X:151961323:A:C	F202L	0.994
X:151961323:A:T	F202L	0.994
X:151961325:A:G	F202L	0.994
X:151961344:G:C	C195W	0.994
X:151961345:C:T	C195Y	0.994
X:151962444:C:A	G181V	0.994
X:151961303:C:G	C209S	0.993
X:151961304:A:T	C209S	0.993
X:151962444:C:T	G181D	0.993
X:151962459:C:G	R176P	0.993

dbSNP variants (sampled 300 via entrez): RS1000100857 (X:151969896 C>A), RS1000220145 (X:151963125 C>T), RS1000298130 (X:151970453 C>T), RS1000313185 (X:151954245 C>T), RS1000391229 (X:151970829 G>A), RS1000940595 (X:151975206 C>T), RS1000996569 (X:151957353 T>C), RS1001246941 (X:151974971 G>A), RS1001269381 (X:151971373 G>C), RS1001272210 (X:151970490 C>G), RS1001321773 (X:151971853 G>A,C), RS1001397434 (X:151961096 C>T), RS1001507319 (X:151967961 A>T), RS1001621640 (X:151971038 C>A), RS1001727263 (X:151963567 C>T)

Disease associations

OMIM: gene MIM:300093 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

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

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 442,649 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1082407	ENZALUTAMIDE	4	9,652
CHEMBL12	DIAZEPAM	4	92,281
CHEMBL1544	LIOTHYRONINE	4	23,700
CHEMBL1568698	GANAXOLONE	4	1,657
CHEMBL207538	BREXANOLONE	4	1,585
CHEMBL3183409	APALUTAMIDE	4	4,076
CHEMBL407	FLUMAZENIL	4	7,150
CHEMBL452	CLONAZEPAM	4	33,297
CHEMBL268254	DELORAZEPAM	2	1,308
CHEMBL275638	FLAVONE	2	88,985
CHEMBL287631	PROGABIDE	2	3,853
CHEMBL454095	ABECARNIL	2	566
CHEMBL8260	BAICALEIN	2	8,592
CHEMBL273481	MUSCIMOL	1	5,759
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1	160,188

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1139916	GABRE		0.00	0

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 875 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	increases expression, decreases expression, increases abundance	3
bisphenol A	affects cotreatment, increases methylation, affects expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Dexamethasone	decreases expression, affects cotreatment	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	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
PCI 5002	increases expression, affects cotreatment	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Azathioprine	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Etomidate	increases activity, increases reaction, affects binding	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)

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