GABRB1

Summary

GABRB1 (gamma-aminobutyric acid type A receptor subunit beta1, HGNC:4081) is a protein-coding gene on chromosome 4p12, encoding Gamma-aminobutyric acid receptor subunit beta-1 (P18505). Beta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 1 subunit. It is mapped to chromosome 4p12 in a cluster comprised of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia.

Source: NCBI Gene 2560 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 45 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 460 total — 1 pathogenic, 4 likely-pathogenic (top 7% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈21% of expected missense variation)
• GTEx eGene: eQTL in 6 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 11
• Drug target: yes — 3 via a complex or family; 18 molecules with ChEMBL bioactivity (top 2% of genes corpus-wide)
• Approved drugs acting on a complex or family including it: 3 — Zaleplon, Zolpidem Tartrate, Zopiclone (GABA A receptor alpha-1/beta-1/gamma-2; GABA-A receptor; agonist GABA site)
• Constraint (gnomAD): pLI 0.73 (intermediate), LOEUF 0.56 (moderately constrained)
• MANE Select transcript: NM_000812

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4081
Approved symbol	GABRB1
Name	gamma-aminobutyric acid type A receptor subunit beta1
Location	4p12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163288
Ensembl biotype	protein_coding
OMIM	137190
Entrez	2560

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000295454

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

ENST00000295454, ENST00000381582, ENST00000509366, ENST00000510909, ENST00000513567, ENST00001110893, ENST00001117790, ENST00001117791, ENST00001122624, ENST00001122625, ENST00001135484

RefSeq mRNA: 1 — MANE Select: NM_000812 NM_000812

CCDS: CCDS3474

Canonical transcript exons

ENST00000295454 — 9 exons

Exon	Start	End
ENSE00001073035	47406682	47406926
ENSE00001073036	47403318	47403455
ENSE00001256142	47425674	47426447
ENSE00001256151	47031567	47031731
ENSE00001699775	47403559	47403711
ENSE00003529257	47161249	47161469
ENSE00003545793	47320127	47320209
ENSE00003661430	47032417	47032484
ENSE00003667582	47031914	47032005

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 98.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.4617 / max 645.9126, expressed in 177 samples.

Highest expression (Bgee): Brodmann (1909) area 23, middle temporal gyrus, entorhinal cortex, substantia nigra pars reticulata, dorsal motor nucleus of vagus nerve.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GABRB1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

7 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Heart Left Ventricle	eqtl	1.1e-08	-0.27	4:47011092:G:A
Heart Atrial Appendage	eqtl	3.6e-05	-0.24	4:47017604:T:C
Artery Tibial	eqtl	1.0e-03	-0.17	4:47010019:C:G
Artery Coronary	eqtl	1.9e-03	-1.26	4:46401619:G:A
Brain Nucleus accumbens basal ganglia	sqtl	8.2e-03	+0.53	4:47191127:C:A
Colon Sigmoid	eqtl	2.0e-02	-0.26	4:47065905:A:G
Brain Nucleus accumbens basal ganglia	eqtl	3.9e-02	+0.83	4:47001344:G:A

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
47545	3.1164	155
47546	0.7927	108
47543	0.1360	66
47540	0.1252	54
47542	0.1159	53
47544	0.1124	64
47541	0.0631	43

Top tissues by expression

showing 100 of 281 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	98.83	gold quality
middle temporal gyrus	UBERON:0002771	98.63	gold quality
entorhinal cortex	UBERON:0002728	98.47	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.47	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.46	gold quality
parietal lobe	UBERON:0001872	96.34	gold quality
endothelial cell	CL:0000115	96.33	gold quality
postcentral gyrus	UBERON:0002581	96.22	gold quality
CA1 field of hippocampus	UBERON:0003881	96.15	gold quality
substantia nigra pars compacta	UBERON:0001965	95.48	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.22	gold quality
lateral globus pallidus	UBERON:0002476	95.15	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.78	gold quality
ventral tegmental area	UBERON:0002691	94.29	gold quality
superior frontal gyrus	UBERON:0002661	94.28	gold quality
superior vestibular nucleus	UBERON:0007227	94.14	gold quality
frontal pole	UBERON:0002795	94.10	gold quality
middle frontal gyrus	UBERON:0002702	93.32	gold quality
orbitofrontal cortex	UBERON:0004167	93.16	gold quality
medulla oblongata	UBERON:0001896	92.95	gold quality
inferior olivary complex	UBERON:0002127	91.06	gold quality
pons	UBERON:0000988	90.83	gold quality
buccal mucosa cell	CL:0002336	89.91	gold quality
occipital lobe	UBERON:0002021	87.32	gold quality
temporal lobe	UBERON:0001871	86.86	gold quality
corpus callosum	UBERON:0002336	85.85	gold quality
cerebellar vermis	UBERON:0004720	85.76	gold quality
primary visual cortex	UBERON:0002436	84.51	gold quality
paraflocculus	UBERON:0005351	84.39	gold quality
globus pallidus	UBERON:0001875	83.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.06	gold quality
frontal cortex	UBERON:0001870	82.95	gold quality
subthalamic nucleus	UBERON:0001906	82.65	gold quality
nucleus accumbens	UBERON:0001882	82.60	gold quality
telencephalon	UBERON:0001893	82.47	gold quality
cerebral cortex	UBERON:0000956	82.30	gold quality
neocortex	UBERON:0001950	81.87	gold quality
dorsal plus ventral thalamus	UBERON:0001897	81.83	gold quality
forebrain	UBERON:0001890	81.52	gold quality
caudate nucleus	UBERON:0001873	81.16	gold quality
prefrontal cortex	UBERON:0000451	80.96	gold quality
putamen	UBERON:0001874	80.72	gold quality
Ammon’s horn	UBERON:0001954	80.57	gold quality
medial globus pallidus	UBERON:0002477	80.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.25	gold quality
brain	UBERON:0000955	80.22	gold quality
midbrain	UBERON:0001891	79.77	gold quality
central nervous system	UBERON:0001017	79.69	gold quality
amygdala	UBERON:0001876	78.96	gold quality
cingulate cortex	UBERON:0003027	78.88	gold quality
anterior cingulate cortex	UBERON:0009835	78.77	gold quality
substantia nigra	UBERON:0002038	78.68	gold quality
inferior vagus X ganglion	UBERON:0005363	78.37	gold quality
hypothalamus	UBERON:0001898	77.94	gold quality
lateral nuclear group of thalamus	UBERON:0002736	77.86	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.84	gold quality
right frontal lobe	UBERON:0002810	75.27	gold quality
pituitary gland	UBERON:0000007	74.02	gold quality
ventricular zone	UBERON:0003053	71.53	gold quality
adenohypophysis	UBERON:0002196	71.19	gold quality
ganglionic eminence	UBERON:0004023	70.00	gold quality
cerebellum	UBERON:0002037	69.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.21	gold quality
synovial joint	UBERON:0002217	67.61	silver quality
right hemisphere of cerebellum	UBERON:0014890	67.37	gold quality
cerebellar cortex	UBERON:0002129	67.10	gold quality
cerebellar hemisphere	UBERON:0002245	66.80	gold quality
adult organism	UBERON:0007023	66.65	gold quality
heart left ventricle	UBERON:0002084	66.60	gold quality
cardiac ventricle	UBERON:0002082	66.25	gold quality
popliteal artery	UBERON:0002250	65.90	gold quality
tibial artery	UBERON:0007610	65.85	gold quality
cortical plate	UBERON:0005343	64.68	gold quality
apex of heart	UBERON:0002098	64.32	gold quality
left coronary artery	UBERON:0001626	63.52	gold quality
hair follicle	UBERON:0002073	63.39	gold quality
pigmented layer of retina	UBERON:0001782	63.10	gold quality
retina	UBERON:0000966	63.09	gold quality
spinal cord	UBERON:0002240	63.03	gold quality
heart	UBERON:0000948	62.67	gold quality
coronary artery	UBERON:0001621	62.14	gold quality
right coronary artery	UBERON:0001625	61.98	gold quality
embryo	UBERON:0000922	61.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	60.97	gold quality
cranial nerve II	UBERON:0000941	59.48	silver quality
aorta	UBERON:0000947	57.33	gold quality
layer of synovial tissue	UBERON:0007616	56.99	silver quality
decidua	UBERON:0002450	56.55	gold quality
right atrium auricular region	UBERON:0006631	56.24	gold quality
cardiac atrium	UBERON:0002081	55.88	gold quality
choroid plexus epithelium	UBERON:0003911	54.44	silver quality
left ventricle myocardium	UBERON:0006566	54.29	silver quality
ileal mucosa	UBERON:0000331	51.14	silver quality
deltoid	UBERON:0001476	51.02	gold quality
placenta	UBERON:0001987	50.76	gold quality
tibialis anterior	UBERON:0001385	50.68	silver quality
quadriceps femoris	UBERON:0001377	50.32	gold quality
gall bladder	UBERON:0002110	50.22	gold quality
rectum	UBERON:0001052	49.84	gold quality
skin of hip	UBERON:0001554	49.65	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	78.43
E-GEOD-84465	yes	12.08
E-HCAD-25	yes	7.37
E-ANND-3	yes	4.07

HPA expression

RNA tissue specificity: Tissue enhanced

50 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Nucleus accumbens	tissue	100.8
Postcentral gyrus	tissue	72.1
Hippocampus	tissue	70.4
Hippocampal formation	tissue	63.3
Prefrontal cortex	tissue	56.5
Cerebral cortex	tissue	56.5
Retrosplenial and cingulate cortex	tissue	50.4
Motor cortex	tissue	49.0
Retrosplenial cortex	tissue	48.6
Entorhinal cortex	tissue	47.0
Insular cortex	tissue	45.5
Locus coeruleus	tissue	44.3
Hypothalamus	tissue	43.9
Temporal cortex	tissue	42.8
Amygdala	tissue	40.3
Occipital cortex	tissue	39.3
Septum	tissue	39.2
Somatosensory cortex	tissue	38.7
Ventral forebrain	tissue	35.7
Basal ganglia	tissue	29.1
Pons	tissue	28.2
Thalamus	tissue	28.0
Periaqueductal gray	tissue	26.8
Midbrain	tissue	26.4
Substantia nigra	tissue	22.8
Spinal cord	tissue	22.1
Corpus callosum	tissue	21.8
Medulla oblongata	tissue	20.7
Caudate putamen	tissue	20.6
Frontal cortex	tissue	19.1
Putamen	tissue	16.8
Olfactory bulb	tissue	13.3
Superior colliculi	tissue	12.2
Cerebellum	tissue	9.1
Choroid plexus	tissue	5.0
Heart muscle	tissue	3.4
Retina	tissue	2.3
Pituitary gland	tissue	1.4
Kidney	tissue	0.3
Parathyroid gland	tissue	0.2
Gallbladder	tissue	0.2
Rectum	tissue	0.1
Colon	tissue	0.1
Endometrium 1	tissue	0.1
Placenta	tissue	0.1
Thyroid gland	tissue	0.1
Small intestine	tissue	0.1
Duodenum	tissue	0.1
Adrenal gland	tissue	0.1
Fallopian tube	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Temporal pole (104.9), Ventromedial nucleus (104.4), Perirhinal gyrus (104.1), Arcuate nucleus (102.0), Nucleus of the diagonal band (100.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting GABRB1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 64 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AZ-3P	99.82	70.56	3549

Functional genomics

gnomAD constraint: pLI 0.728, LOEUF 0.565, missense Z 3.01 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000295454 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈21% 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
4:47,031,652–47,031,969	56 / 54.8	1.02	no
4:47,031,970–47,403,338	100 / 184.3	0.54	no
4:47,403,339–47,403,441	36 / 39.7	0.91	no
4:47,403,442–47,406,830	37 / 126.3	0.29	yes (p 1.9e-15)
4:47,406,831–47,426,015	181 / 195.6	0.93	no

Literature-anchored findings (GeneRIF, showing 20)

• linkage disequilibrium between beta frequency of EEG and a set of GABA(A) receptor genes (PMID:11891318)
• A signal for GABA A beta 1 isoform mRNA transcript could not be detected in the competitive RT-PCR assay. (PMID:15337300)
• These results confirmed our earlier findings, indicating GABRA4 and GABRB1 as genes contributing to autism susceptibility, extending the effect to multiple ethnic groups and suggesting seizures as a stratifying phenotype. (PMID:16770606)
• histamine modulates heteromultimeric GABA(A) receptors and may thus represent an endogenous ligand for an allosteric site (PMID:18281286)
• three distinct sets of amino acid residues in the N-terminal extracellular domain of the hbeta1 subunit, which when mutated to the homologous residue in hbeta3 allow expression as a functional homomeric receptor (PMID:18650446)
• Gaba (A) beta1 and beta3 subunit mRNA levels in the dorsolateral prefrontal cortex are not altered in schizophrenia. (PMID:20843900)
• Gaba-A receptor subunit beta1 is not involved in amygdala hyperexcitability of patients with temporal lobe epilepsy. (PMID:20848605)
• Data indicate the selectivity of some selected compounds were assessed in recombinant alpha(1)beta(2)gamma(2)L, alpha(2)beta(1)gamma(2)L, and alpha(5)beta(2)gamma(2)L GABA(A) receptors. (PMID:21751815)
• In cases of tramadol-induced death, the expression of GABA(A)alpha1 and GABA(B)1 significantly increased in the medulla oblongata solitary nucleus and ambiguous nucleus. (PMID:22393585)
• These results suggest that epigenetic control of gene expression may affect the expression of GABRB1 and disrupt inhibitory synaptic transmission during embryonic development. (PMID:23392927)
• This study demonstrates altered patterns of N-glycosylation of GABRB1 in the temporal lobe in schizophrenia. (PMID:23917429)
• GABRB1 protein levels were significantly decreased in schizophrenia, major depressive disorder, and bipolar disorder patients’ lateral cerebellum compared to controls. (PMID:24022508)
• study provides the first evidence for the involvement of the GABRB1 gene in the thalamus structure and their interactive effects on intelligence (PMID:25192656)
• Both mRNA and protein of GABAB receptor subunits, GABAB1 and GABAB2, were co-expressed in cultured human RPE cells; GABAB receptors regulate the [Ca2+]i via a pertussis toxin-sensitive Gi/o-protein pathway and a phospholipase C pathway (PMID:25241062)
• PCDHB14- and GABRB1-like nervous system developmental genes are altered during early neuronal differentiation of NCCIT cells treated with ethanol (PMID:25566775)
• This study showed that in male group the expression of GABRB1 was generally lower in schizophrenia cases compared to the control, but was higher in female group. (PMID:25660468)
• No allelic association was detected in this study between tested SNPs and risk for developing alcohol dependence in a British and Irish population; however, modest genotypic associations were found with several intronic GABRbeta1 SNPs that may directly influence alcohol dependence risk or may be in linkage disequilibrium with causal risk variants in nearby genes, including other GABA receptor subunits (PMID:28346242)
• Results from genome-wide DNA methylation, functional network analysis and pyrosequencing, show selective CpG sites (NOS1AP, BID, and GABRB1) differentially methylated in smokers and chronic obstructive pulmonary disease patients compared to nonsmokers. (PMID:28416970)
• MiRNA-384-5p Targets GABRB1 to Regulate Ketamine-Induced Neurotoxicity in Neurons. (PMID:35416273)
• Epileptic Encephalopathy GABRB Structural Variants Share Common Gating and Trafficking Defects. (PMID:38136660)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gabrb1	ENSMUSG00000029212
rattus_norvegicus	Gabrb1	ENSRNOG00000002327

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), 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:95619) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 16 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased bone mineral density	1
decreased body size	1
female infertility	1
alcohol preference	1
abnormal corpus luteum morphology	1
abnormal operant conditioning behavior	1
abnormal single cell response	1
decreased follicle stimulating hormone level	1
decreased luteinizing hormone level	1
decreased thyroid-stimulating hormone level	1
decreased growth hormone level	1
decreased prolactin level	1
abnormal miniature inhibitory postsynaptic currents	1
enhanced behavioral response to alcohol	1
decreased miniature inhibitory postsynaptic current frequency	1
increased miniature inhibitory postsynaptic current amplitude	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
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
Danio rerio	O93430	85.6%	Diamond
Musca domestica	Q75NA5	84.3%	Diamond
Haemonchus contortus	P91730	81.4%	Diamond
Caenorhabditis elegans	Q17328	81.4%	Diamond
Lymnaea stagnalis	P26714	58.6%	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
CORIN	protein-coding	10699
COMMD8	protein-coding	54951
ATP10D	protein-coding	57205
COX7B2	protein-coding	170712
GABRA4	protein-coding	2557

Protein

Protein identifiers

Gamma-aminobutyric acid receptor subunit beta-1 — P18505 (reviewed: P18505)

Alternative names: GABA(A) receptor subunit beta-1

All UniProt accessions (3): D6REM0, P18505, X5DNL6

UniProt curated annotations — full annotation on UniProt →

Function. Beta 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 one or two GABA active binding sites located at the alpha and beta subunit interfaces, depending on subunit composition. When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission. Beta-containing GABAARs can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness.

Subunit / interactions. Heteropentamer, formed by a combination of alpha (GABRA1-6), beta (GABRB1-3), gamma (GABRG1-3), delta (GABRD), epsilon (GABRE), rho (GABRR1-3), pi (GABRP) and theta (GABRQ) chains, each subunit exhibiting distinct physiological and pharmacological properties. Binds UBQLN1.

Subcellular location. Postsynaptic cell membrane. Cell membrane.

Disease relevance. Developmental and epileptic encephalopathy 45 (DEE45) [MIM:617153] 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Potentiated by etomidate, propofol, pregnanolone and flurazepam. Potentiated by histamine.

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. GABRB1 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P18505-1	1	yes
P18505-2	2, B

RefSeq proteins (1): NP_000803* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002289	GABAAb_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 (55 total): strand 16, helix 13, binding site 5, sequence variant 4, transmembrane region 4, glycosylation site 2, splice variant 2, topological domain 2, sequence conflict 2, turn 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
9CXB	Native human GABAA receptor of beta2-alpha1-beta1-alpha2-gamma2 assembly	ELECTRON MICROSCOPY	3.33
9CTV	Native human GABAA receptor of beta2-alpha1-gamma2-beta1-alpha2 assembly	ELECTRON MICROSCOPY	3.36
9CXD	Native human GABAA receptor of beta2-alpha1-beta1-beta1-gamma2 assembly	ELECTRON MICROSCOPY	3.36

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18505-F1	78.01	0.57

Antibody-complex structures (SAbDab)

3 antibodies co-crystallized with this protein: 9CTV, 9CXB, 9CXD

Human Protein Atlas

Protein class: 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.

Ligand- & substrate-binding residues (5)

Position	Role
182	4-aminobutanoate
227	4-aminobutanoate
227	histamine
122	histamine
181–182	histamine

Disulfide bonds (1)

Type	Positions
Disulfide bond	161–175

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	105, 174

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: 238 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_274, TGCGCANK_UNKNOWN, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, GOBP_NEUROGENESIS, GOBP_CELL_CELL_SIGNALING, chr4p12, GOBP_CHLORIDE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION, GOBP_RESPONSE_TO_KETONE, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, WTGAAAT_UNKNOWN, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION

GO Biological Process (18): monoatomic ion transport (GO:0006811), signal transduction (GO:0007165), gamma-aminobutyric acid signaling pathway (GO:0007214), response to toxic substance (GO:0009636), central nervous system neuron development (GO:0021954), negative regulation of synaptic transmission, GABAergic (GO:0032229), response to progesterone (GO:0032570), ovulation cycle (GO:0042698), synaptic transmission, GABAergic (GO:0051932), cellular response to histamine (GO:0071420), extrasynaptic signaling via GABA (GO:0160001), chloride transmembrane transport (GO:1902476), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220), regulation of membrane potential (GO:0042391), regulation of postsynaptic membrane potential (GO:0060078), monoatomic anion transmembrane transport (GO:0098656), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (13): GABA-A receptor activity (GO:0004890), ligand-gated monoatomic ion channel activity (GO:0015276), GABA-gated chloride ion channel activity (GO:0022851), GABA receptor binding (GO:0050811), ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential (GO:0099507), 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), monoatomic anion channel activity (GO:0005253), chloride channel activity (GO:0005254), neurotransmitter receptor activity (GO:0030594), G protein-coupled neurotransmitter receptor activity (GO:0099528)

GO Cellular Component (12): nuclear envelope (GO:0005635), plasma membrane (GO:0005886), dendrite (GO:0030425), chloride channel complex (GO:0034707), presynaptic active zone membrane (GO:0048787), Schaffer collateral - CA1 synapse (GO:0098685), GABA-ergic synapse (GO:0098982), postsynaptic specialization membrane (GO:0099634), GABA-A receptor complex (GO:1902711), membrane (GO:0016020), signaling receptor complex (GO:0043235), postsynaptic membrane (GO:0045211)

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

showing 60 of 66 GO namespaces:

Category	Terms
synaptic membrane	3
GABA receptor activity	2
monoatomic anion transport	2
monoatomic ion transmembrane transport	2
regulation of membrane potential	2
monoatomic ion channel activity	2
transmitter-gated monoatomic ion channel activity	2
ligand-gated monoatomic ion channel activity	2
presynaptic membrane	2
signaling receptor activity	2
synapse	2
transport	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell-cell signaling	1
response to chemical	1
central nervous system neuron differentiation	1
neuron development	1
regulation of synaptic transmission, GABAergic	1
negative regulation of synaptic transmission	1
synaptic transmission, GABAergic	1
response to steroid hormone	1
response to ketone	1
rhythmic process	1
multicellular organismal reproductive process	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
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
regulation of biological quality	1
ligand-gated channel activity	1
chloride channel activity	1
ligand-gated monoatomic anion channel activity	1
signaling receptor binding	1
regulation of presynaptic membrane potential	1
regulation of postsynaptic membrane potential	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic anion transmembrane transporter activity	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
G protein-coupled receptor activity	1
neurotransmitter receptor activity	1
nucleus	1
endomembrane system	1
organelle envelope	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
monoatomic ion channel complex	1
presynaptic active zone	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 44 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
chloride transmembrane transport	BP	direct assay
gamma-aminobutyric acid signaling pathway	BP	mutant phenotype
GABA-A receptor complex	CC	direct assay
plasma membrane	CC	direct assay
GABA-A receptor activity	MF	direct assay
GABA-gated chloride ion channel activity	MF	direct assay
ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 1,244 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABRB1	PGM1	P36871	549
GABRB1	COMMD8	Q9NX08	542
GABRB1	GABBR2	O75899	512
GABRB1	AHI1	Q8N157	493
GABRB1	GABRG1	Q8N1C3	471
GABRB1	RGS12	O14924	452
GABRB1	GABRA2	P47869	451
GABRB1	GRIK2	Q13002	445
GABRB1	GAD1	Q99259	443
GABRB1	GABRA4	P48169	441
GABRB1	RYR3	Q15413	438
GABRB1	SYNGAP1	Q96PV0	438
GABRB1	NPY1R	P25929	426
GABRB1	GRIA2	P42262	425
GABRB1	GABRA1	P14867	420
GABRB1	GAD2	Q05329	420

IntAct

Human interaction partners of GABRB1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
FKBP5	physical association	0.400	1
NEUROD4	physical association	0.370	1
NOD1	physical association	0.370	1

BioGRID (9 interactions; top human partners by supporting records): HSPA8 (Affinity Capture-Luminescence; 2 records), CUL1 (Affinity Capture-MS), NEUROD4 (Two-hybrid), NOD1 (Two-hybrid), PARP12 (Proximity Label-MS), PARP2 (Proximity Label-MS), PRNP (Affinity Capture-MS), UBQLN1 (Two-hybrid)

SIGNOR signaling

6 signaling interactions:

A	Effect	B	Mechanism
GABRB1	“form complex”	“GABA-A (a1-b1-g2) receptor”	binding
GABRB1	“form complex”	“GABA-A (a2-b1-g2) receptor”	binding
GABRB1	“form complex”	“GABA-A (a3-b1-g2) receptor”	binding
GABRB1	“form complex”	“GABA-A (a4-b1-g2) receptor”	binding
GABRB1	“form complex”	“GABA-A (a6-b1-g2) receptor”	binding
GABRB1	“form complex”	“GABA-A (a5-b1-g2) receptor”	binding

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

Disease & clinical

Genetic variants

Variant evidence for GABRB1: 460 ClinVar records (5 pathogenic / likely pathogenic); 10 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	4
Uncertain significance	227
Likely benign	194
Benign	18

Top pathogenic / likely-pathogenic (5)

Showing all 5 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
265864	NM_000812.4(GABRB1):c.860C>T (p.Thr287Ile)	Likely pathogenic	criteria provided, single submitter	2
984675	NM_000812.4(GABRB1):c.740T>C (p.Ile247Thr)	Likely pathogenic	criteria provided, single submitter	2
431076	NM_000812.4(GABRB1):c.157C>T (p.Arg53Trp)	Likely pathogenic	criteria provided, single submitter	1
982940	NM_000812.4(GABRB1):c.854C>A (p.Thr285Lys)	Likely pathogenic	criteria provided, single submitter	1
265863	NM_000812.4(GABRB1):c.737T>C (p.Phe246Ser)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore GABRB1’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; 34 predictions of 1,237):

Position(s)	Effect	Δscore	Sites
4:47032006–47032007	donor_loss	1.0000	2
4:47032415–47032416	acceptor_loss	1.0000	6
4:47032485–47032486	donor_loss	1.0000	5
4:47161248	acceptor_loss	1.0000	2
4:47161470–47161471	donor_loss	1.0000	6
4:47320123	acceptor_gain	1.0000
4:47320125–47320126	acceptor_loss	1.0000	6
4:47320215	donor_gain	1.0000
4:47403309–47403310	acceptor_gain	1.0000	2
4:47403316–47403317	acceptor_loss	1.0000	3

AlphaMissense

1,728 missense substitutions predicted likely pathogenic (of 3,126 scored), across 339 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
M80	9	0.980	1.000
M163	9	0.974	1.000
M286	9	0.963	0.999
M140	9	0.935	0.998
M311	9	0.854	0.997
D450	8	1.000	1.000
D94	8	0.999	1.000
D120	8	0.999	1.000
D171	8	0.999	1.000
D307	8	0.999	1.000
D109	8	0.998	1.000
H132	8	0.998	0.999
N138	8	0.998	1.000
F265	8	0.998	1.000
F318	8	0.997	1.000
D49	8	0.996	0.999
D81	8	0.994	0.999
D126	8	0.993	0.999
D188	8	0.992	0.998
N328	8	0.990	1.000

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Glioblastoma Multiforme)

Disease associations

OMIM: gene MIM:137190 | disease phenotypes: MIM:617153

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
developmental and epileptic encephalopathy, 45	Strong	Autosomal dominant	3

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Limited	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
Early onset or syndromic epilepsy	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (1): developmental and epileptic encephalopathy, 45 (MONDO:0014942)

HPO phenotypes

11 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0002079	Hypoplasia of the corpus callosum
HP:0002376	Developmental regression
HP:0002521	Hypsarrhythmia
HP:0003593	Infantile onset
HP:0100704	Cerebral visual impairment
HP:0200134	Epileptic encephalopathy

GWAS associations

10 associations:

Study	Trait	p-value
GCST007325_261	General risk tolerance (MTAG)	5e-14
GCST007324_13	Adventurousness	7e-12
GCST007096_116	Pulse pressure	1e-8
GCST004967_2	Moderate or severe diarrhoea in darapladib-treated cardiovascular disease (time to event)	3e-8
GCST012489_69	Heel bone mineral density x serum urate levels interaction	3e-8
GCST007099_231	Systolic blood pressure	4e-7
GCST004833_2	Cervical cancer	1e-6
GCST001762_176	Obesity-related traits	5e-6
GCST006088_49	Familial squamous cell lung carcinoma	5e-6
GCST005231_28	Major depressive disorder	7e-6

EFO canonical traits (from GWAS)

8 canonical traits:

EFO ID	Trait name
EFO:0004338	body weight
EFO:0008395	response to darapladib
EFO:0006953	family history of lung cancer
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0008579	risk-taking behaviour
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL2093872 (PROTEIN COMPLEX GROUP), CHEMBL2109244 (PROTEIN COMPLEX GROUP), CHEMBL2111392 (PROTEIN COMPLEX), CHEMBL3885570 (PROTEIN COMPLEX), CHEMBL4296045 (PROTEIN COMPLEX), CHEMBL4523639 (PROTEIN COMPLEX), CHEMBL4558 (SINGLE PROTEIN), CHEMBL5291949 (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 GABRB1 — the drug acts on the assembly or class, not necessarily on this subunit alone.

3 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
ZOPICLONE	GABA-A receptor; agonist GABA site	9	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 578,068 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

18 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
CHEMBL15891	LINDANE	4	83,776
CHEMBL1544	LIOTHYRONINE	4	23,991
CHEMBL526	PROPOFOL	4	29,086
CHEMBL911	ZOLPIDEM	4	17,964
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)

PharmGKB variant annotations

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

2 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs16860087	antipsychotics	Dosage	Allele A is associated with increased dose of antipsychotics in people with schizoaffective disorder and Schizophrenia as compared to allele C.	PMID:26780210
rs4627835	antipsychotics	Dosage	Allele T is associated with increased dose of antipsychotics in people with schizoaffective disorder and Schizophrenia as compared to allele A.	PMID:26780210

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — GABA_A receptors

Binding affinities (BindingDB)

21 measured of 33 human assays (39 total across all organisms); most potent 21 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide	KI	2.2 nM
CHEMBL5072077	EC50	60 nM
CHEMBL5088746	EC50	140 nM
CHEMBL5081682	EC50	160 nM
GANAXOLONE	EC50	200 nM
CHEMBL5186739	IC50	245 nM
CHEBI:70620	EC50	320 nM
CHEMBL5090382	EC50	1100 nM
CHEMBL5086854	IC50	1500 nM
CHEMBL5069550	EC50	1920 nM
CHEMBL5187612	IC50	4900 nM
CHEMBL5177970	IC50	6760 nM
4-Chloro-2,6-diisopropyl-phenol	EC50	10000 nM
CHEMBL4587325	EC50	10000 nM
CHEMBL4560044	EC50	11000 nM
4-Bromo-2,6-diisopropyl-phenol	EC50	12000 nM
4-Iodo-2,6-diisopropylphenol	EC50	12000 nM
CHEMBL5204910	IC50	13200 nM
(4-Hydroxy-3,5-diisopropyl-phenyl)-phenyl-methanone	EC50	47000 nM
propofol	KI	98900 nM
CHEMBL4540194	EC50	271000 nM

ChEMBL bioactivities

558 potent at pChembl≥5 of 619 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
9.57	Ki	0.27	nM	CHEMBL381059
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

PubChem BioAssay actives

488 with measured affinity, of 1148 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 6-benzyl-4-oxo-1H-quinoline-3-carboxylate	262560: Displacement of [3H]Flumazenil from human GABA-Aalpha1 receptor plus beta-2-gamma-2 expressed in HEK293 cells	ki	0.0003	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
3-methylbutyl 6-ethyl-4-oxo-1H-quinoline-3-carboxylate	262560: Displacement of [3H]Flumazenil from human GABA-Aalpha1 receptor plus beta-2-gamma-2 expressed in HEK293 cells	ki	0.0041	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
gamma-Aminobutyric Acid	affects binding, increases activity, increases reaction, decreases reaction	6
Valproic Acid	affects cotreatment, increases expression, affects expression	6
bisphenol A	decreases expression, increases methylation	2
fipronil	affects binding, decreases activity	2
Hexachlorocyclohexane	affects binding, decreases reaction, increases activity	2
Enflurane	increases activity, increases reaction, affects binding, decreases reaction	2
Lead	affects expression, affects methylation	2
Propofol	affects binding, increases activity, increases reaction	2
bisphenol F	increases expression	1
sodium arsenite	affects methylation	1
picrotoxinin	affects binding, decreases reaction, increases activity	1
1,1,1-trichloroethane	affects binding, increases activity, increases reaction	1
tribromoethanol	increases reaction, affects binding, increases activity	1
delta-hexachlorocyclohexane	affects binding, increases activity, increases reaction, decreases activity	1
1-(4-ethynylphenyl)-4-propyl-2,6,7-trioxabicyclo(2.2.2)octane	increases reaction, affects binding	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sevoflurane	affects binding, increases activity, increases reaction	1
Felbamate	affects binding, decreases activity	1
Ethanol	decreases expression	1
Azacitidine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Bicuculline	affects binding, decreases activity	1
Chloral Hydrate	increases activity, increases reaction, affects binding	1
Chloralose	affects binding, increases activity, increases reaction, decreases reaction	1
Chlorobutanol	affects binding, increases activity, increases reaction	1
Diazepam	affects binding, increases activity	1
Diethylhexyl Phthalate	decreases expression	1
Endosulfan	affects binding	1

ChEMBL screening assays

266 unique, capped per target: 219 binding, 39 functional, 5 admet, 3 toxicity

Representative assays (with source publication via chembl_document):

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

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for GABRB1 across ~30M SureChEMBL compounds — explore on Sugi Predict.