GABBR1

Summary

GABBR1 (gamma-aminobutyric acid type B receptor subunit 1, HGNC:4070) is a protein-coding gene on chromosome 6p22.1, encoding Gamma-aminobutyric acid type B receptor subunit 1 (Q9UBS5). Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2.

This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined.

Source: NCBI Gene 2550 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with language delay and variable cognitive abnormalities (Strong, GenCC)
• GWAS associations: 34
• Clinical variants (ClinVar): 190 total — 7 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001470

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4070
Approved symbol	GABBR1
Name	gamma-aminobutyric acid type B receptor subunit 1
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	hGB1a, GPRC3A
Ensembl gene	ENSG00000204681
Ensembl biotype	protein_coding
OMIM	603540
Entrez	2550

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 8 protein_coding, 8 retained_intron, 5 nonsense_mediated_decay

ENST00000355973, ENST00000377012, ENST00000377016, ENST00000377034, ENST00000462632, ENST00000467259, ENST00000472823, ENST00000473774, ENST00000476670, ENST00000477029, ENST00000478931, ENST00000485508, ENST00000486434, ENST00000488334, ENST00000489385, ENST00000489839, ENST00000491829, ENST00000494634, ENST00000494877, ENST00000706533, ENST00000967932

RefSeq mRNA: 4 — MANE Select: NM_001470 NM_001319053, NM_001470, NM_021903, NM_021904

CCDS: CCDS4663, CCDS4664, CCDS4665

Canonical transcript exons

ENST00000377034 — 23 exons

Exon	Start	End
ENSE00001681344	29632850	29633183
ENSE00001690881	29630458	29630643
ENSE00001941741	29602238	29603716
ENSE00003458297	29609229	29609379
ENSE00003469119	29604494	29604637
ENSE00003494045	29610924	29611001
ENSE00003507541	29606897	29607004
ENSE00003553864	29607102	29607218
ENSE00003559590	29622104	29622205
ENSE00003561995	29623890	29624024
ENSE00003565333	29608601	29608733
ENSE00003581880	29621752	29621817
ENSE00003588707	29631396	29631599
ENSE00003607880	29606391	29606484
ENSE00003625776	29613243	29613485
ENSE00003643298	29612551	29612614
ENSE00003656727	29629087	29629107
ENSE00003663738	29604860	29604988
ENSE00003672249	29623305	29623475
ENSE00003676962	29627486	29627646
ENSE00003689945	29605569	29605696
ENSE00003692827	29621101	29621292
ENSE00003758771	29632301	29632385

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 99.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0853 / max 409.8574, expressed in 1422 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72461	8.1818	566
72470	4.7541	1232
72467	0.4133	217
72463	0.4060	110
72468	0.3771	191
72469	0.3204	154
72464	0.2236	81
72460	0.1770	82
72462	0.1423	81
72465	0.0669	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.05	gold quality
cerebellar hemisphere	UBERON:0002245	98.90	gold quality
right frontal lobe	UBERON:0002810	98.68	gold quality
cerebellar cortex	UBERON:0002129	98.66	gold quality
anterior cingulate cortex	UBERON:0009835	98.50	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.47	gold quality
body of uterus	UBERON:0009853	98.27	gold quality
cortical plate	UBERON:0005343	98.00	gold quality
right ovary	UBERON:0002118	97.93	gold quality
endocervix	UBERON:0000458	97.77	gold quality
left uterine tube	UBERON:0001303	97.71	gold quality
left ovary	UBERON:0002119	97.70	gold quality
mucosa of stomach	UBERON:0001199	97.57	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.40	gold quality
lower esophagus	UBERON:0013473	97.38	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.35	gold quality
descending thoracic aorta	UBERON:0002345	96.87	gold quality
ascending aorta	UBERON:0001496	96.64	gold quality
thoracic aorta	UBERON:0001515	96.64	gold quality
right coronary artery	UBERON:0001625	96.61	gold quality
adenohypophysis	UBERON:0002196	96.57	gold quality
tibial nerve	UBERON:0001323	96.55	gold quality
ectocervix	UBERON:0012249	96.49	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.49	gold quality
aorta	UBERON:0000947	95.83	gold quality
cerebellum	UBERON:0002037	95.69	gold quality
popliteal artery	UBERON:0002250	95.58	gold quality
tibial artery	UBERON:0007610	95.58	gold quality
left coronary artery	UBERON:0001626	95.56	gold quality
hypothalamus	UBERON:0001898	95.53	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting GABBR1, 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-6798-5P	100.00	65.77	699
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-3978	99.24	68.39	2201

Literature-anchored findings (GeneRIF, showing 40)

• Alterations in inhibitory synaptic transmission through GABA(B)R1 appears to affect differentially certain hippocampal circuits in a population of epileptic patients and could contribute to the pathophysiology of temporal lobe epilepsy. (PMID:12115687)
• The intracellular loops of the GB2 subunit are crucial for G-protein coupling of the heteromeric gamma-aminobutyrate B receptor. (PMID:12130687)
• evidence that the translated polymorphism of exon 7 may be functionally meaningful and impact cortical EEG oscillations (PMID:12555235)
• The GABA(B[1]) polymorphism (G1465A) confers a highly increased susceptibility to temporal lobe epilepsy. Moreover, it seems to influence the severity of this common epileptic disorder (PMID:12601092)
• Post hoc analyses showed an association between EEG phenotype and exon 7 genotype in normal subjects only. (PMID:12645817)
• GABBR1 gene might not be a susceptibility gene for childhood absence epilepsy at least in the Chinese population (PMID:12770685)
• GHB, administered in vivo, reduces MAP kinase phosphorylation via a direct activation of GABAB receptors by GHB, but was found ineffective on MAP kinase phosphorylation in brain slices (PMID:12923192)
• Increased expression of GABA(B) receptor subtype 1 indicates augmented presynaptic inhibition of glutamate release as a possible protective mechanism in temporal lobe epilepsy. (PMID:14625043)
• Altered GABA(B1a) receptor mRNA expression occurs in human temporal lobe epilepsy; possibly the observed changes may also serve to counteract ongoing hyperexcitability. (PMID:14643764)
• GABAB receptor cell surface stability is modulated by phosphorylation and chronic agonist treatment (PMID:14707142)
• GABA(B) receptor subunit GABA(B)R1 is found on the same neurons and follows the same distribution patterns in the basal ganglia as the GABABR2 receptor subunit. (PMID:14961561)
• Association of the GABA(B)R1 with the GABA(A) receptor gamma2S subunit robustly promotes cell surface expression of GABA(B)R1 in the absence of GABA(B)R2, that is usually required for efficient trafficking of GABA(B)R1 to the cell surface. (PMID:14966130)
• The GABA(B) receptor may be present as a heterodimer with subunits of GABA(B1) and GABA(B2) in the human colon. (PMID:14978362)
• Data show that the two CCP modules of the GABA(B) 1a receptor have strikingly different structural properties, reflecting their different functions. (PMID:15304491)
• The simultaneous blockade of GABAA and GABAB receptors suppressed acrosome reaction induced by follicular fluid(FF). GABA receptors may play role in sperm activation. This may shed further light on mechanism of FF action on human sperm acrosome reaction. (PMID:15474078)
• identification of the minimal functional domain which still binds a competitive radioligand and leads to a functional, GABA-responding receptor when co-expressed with GABA(B2) (PMID:15482257)
• The observed trends suggest that further investigations of the role of the GABBR1 gene in obsessive-compulsive disorder are warranted. (PMID:15685626)
• The changes in hippocampal GBR1 may reflect alterations in the balance between excitatory and inhibitory neurotransmitter systems, which likely contributes to dysfunction of hippocampal circuitry in Alzheimer disease. (PMID:15759131)
• Temporal lobe epilepsy preceded by febrile seizures is not associated with the polymorphisms or mutations in the GABBR1 gene. (PMID:15799783)
• positive allosteric modulators bind a single subunit of (B) receptor (metabotropic glutamate receptor) dimers (PMID:15863499)
• COPI and 14-3-3 specifically bind to the GB1 RSR sequence and that COPI is involved in its intracellular retention (PMID:16176975)
• Functional GABA(B) receptors are expressed in human airway smooth muscle cells (PMID:16829628)
• the Ala20Val polymorphism of the GABA(B)R1 gene may be associated with obstructive sleep apnea syndrome(OSAS);Gly489Ser polymorphism does not seem to be involved in OSAS; C/C variant of the Phe658Phe polymorphism GABA(B)R1 gene seems associated with OSAS (PMID:17264536)
• CaRs and GABA-B-R subunits can form heteromeric complexes in cells, and their interactions affect cell surface expression and signaling of CaR, which may contribute to extracellular Ca(2+)-dependent receptor activation in target tissues (PMID:17591780)
• Data suggest the stimulation of GABA B R signaling as a novel target for the treatment and prevention of pancreatic cancer. (PMID:18098271)
• The genotype distribution varied significantly between patients and controls. Heterozygous carriers of the A-allele had a 10-fold increase in risk for MTLE-HS (OR 10.01; 95% CI 3.98-25.18, p=3.788E-08). (PMID:18255321)
• no significant association between the GABBR1 c.1456G>A polymorphism and sporadic or familial temporal lobe epilepsy (PMID:18355961)
• GABA may modulate an uncharacterized signaling cascade via GABA(B) receptors coupled to G(i) protein in airway epithelium (PMID:18403780)
• No evidence of significant allelic, genotypic, or haplotypic associations were identified in the tag SNPs of the GABBR1 gene in patients with MTLE, and the polymorphism at G1465A was not observed in samples of this study. (PMID:18653317)
• Levels of GABBR1 are significantly decreased in brains of patients with autism compared with normal brains. (PMID:19002745)
• GABA-B(1A) receptors are able to activate the ERK1/2 pathway despite the absence of surface targetting partner GABA-B(2) (PMID:19052921)
• Data show that GABA is a potent chemoattractant of HUCB stem/progenitor cells specifically through GABA(B)R activation. (PMID:19327013)
• variants of GABBR1 and GABBR2 are associated with nicotine dependence in European- and African-American populations (PMID:19763258)
• GABAB1 subunits interact with DGCR6 in the endoplasmic reticulum prior to their recruitment into functional GABAB receptors. (PMID:20036641)
• Significant reductions in GABA(B) receptor subunit 1 density are demonstrated in cingulate cortex and fusiform gyrus from patients with autism compared to controls. (PMID:20557420)
• This chapter summarizes current understanding of the molecular function of the GABA(B) receptor and recent developments in the identification of allosteric modulators. (PMID:20655478)
• This chapter focuses on the recently emerged mechanisms of GABA(B) receptor exocytosis, endocytosis, recycling, and degradation. (PMID:20655479)
• The role that this phosphorylation plays in determining GABA(B)R effector coupling and their trafficking within the endocytic pathway, is discussed. (PMID:20655480)
• The relationships between the GABA(B) receptor, its effectors and associated proteins that mediate GABA(B) receptor function within the brain, is described. (PMID:20655481)
• Current knowledge on a new role of GABA(B)R as an ambience-dependent regulator of synaptic signaling, is presented. (PMID:20655482)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabbr1b	ENSDARG00000016667
danio_rerio	gabbr1a	ENSDARG00000018967
mus_musculus	Gabbr1	ENSMUSG00000024462
rattus_norvegicus	Gabbr1	ENSRNOG00000000774
drosophila_melanogaster	GABA-B-R1	FBGN0260446
caenorhabditis_elegans		WBGENE00021528

Paralogs (2): GABBR2 (ENSG00000136928), GPR156 (ENSG00000175697)

Protein

Protein identifiers

Gamma-aminobutyric acid type B receptor subunit 1 — Q9UBS5 (reviewed: Q9UBS5)

All UniProt accessions (9): A0A1U9X7R0, C9J342, C9JZG6, Q9UBS5, F8WAS6, F8WAV2, F8WDC0, F8WF38, Q5SUJ9

UniProt curated annotations — full annotation on UniProt →

Function. Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Calcium is required for high affinity binding to GABA. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception. Activated by (-)-baclofen, cgp27492 and blocked by phaclofen. Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.

Subunit / interactions. Heterodimer of GABBR1 and GABBR2. Homodimers may form, but are inactive. Isoform 1E (without C-terminal intracellular domain) is unable to dimerize via a coiled-coil interaction with GABBR2. Interacts (via C-terminus) with ATF4 (via leucine zipper domain). Interacts with JAKMIP1.

Subcellular location. Cell membrane. Postsynaptic cell membrane. Cell projection. Dendrite Secreted.

Tissue specificity. Highly expressed in brain. Weakly expressed in heart, small intestine and uterus. Isoform 1A: Mainly expressed in granular cell and molecular layer. Isoform 1B: Mainly expressed in Purkinje cells. Isoform 1E: Predominantly expressed in peripheral tissues as kidney, lung, trachea, colon, small intestine, stomach, bone marrow, thymus and mammary gland.

Disease relevance. Neurodevelopmental disorder with language delay and variable cognitive abnormalities (NEDLC) [MIM:620502] An autosomal dominant disorder characterized by language delay ranging from mild to severe, varying degrees of intellectual disability, and learning difficulties. Additional features include early motor delay, muscular hypotonia, behavioral abnormalities, sleep disorders, and seizures. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR2. The linker region between the transmembrane domain 3 (TM3) and the transmembrane domain 4 (TM4) probably plays a role in the specificity for G-protein coupling.

Miscellaneous. Major isoform in almost all peripheral tissues, although containing a premature stop codon in the mRNA and thus being a potential target for nonsense-mediated mRNA decay. May act as an antagonist of GABA-B receptors, being able to disrupt the normal association between isoform 1A and GABBR2.

Similarity. Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9UBS5-1	1A	yes
Q9UBS5-2	1B
Q9UBS5-3	1C
Q9UBS5-4	1D
Q9UBS5-5	1E, Truncated

RefSeq proteins (4): NP_001305982, NP_001461, NP_068703, NP_068704 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR001828	ANF_lig-bd_rcpt	Domain
IPR002455	GPCR3_GABA-B	Family
IPR002456	GPCR_3_GABA_rcpt_B1	Family
IPR017978	GPCR_3_C	Domain
IPR028082	Peripla_BP_I	Homologous_superfamily
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily

Pfam: PF00003, PF00084, PF01094

UniProt features (145 total): strand 31, helix 27, binding site 14, turn 10, topological domain 8, sequence conflict 8, transmembrane region 7, glycosylation site 7, sequence variant 7, mutagenesis site 6, disulfide bond 4, splice variant 4, region of interest 3, domain 2, compositionally biased region 2, modified residue 2, signal peptide 1, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
4PAS	X-RAY DIFFRACTION	1.62
4MS4	X-RAY DIFFRACTION	1.9
4MR7	X-RAY DIFFRACTION	2.15
4MR8	X-RAY DIFFRACTION	2.15
4MQF	X-RAY DIFFRACTION	2.22
4MS1	X-RAY DIFFRACTION	2.25
4MQE	X-RAY DIFFRACTION	2.35
4MR9	X-RAY DIFFRACTION	2.35
4MS3	X-RAY DIFFRACTION	2.5
4MRM	X-RAY DIFFRACTION	2.86
7C7S	ELECTRON MICROSCOPY	2.9
7C7Q	ELECTRON MICROSCOPY	3
6W2Y	ELECTRON MICROSCOPY	3.2
6WIV	ELECTRON MICROSCOPY	3.3
7EB2	ELECTRON MICROSCOPY	3.5
7CUM	ELECTRON MICROSCOPY	3.52
6W2X	ELECTRON MICROSCOPY	3.6
6UO8	ELECTRON MICROSCOPY	3.63
6VJM	ELECTRON MICROSCOPY	3.97
7CA3	ELECTRON MICROSCOPY	4.5
6UO9	ELECTRON MICROSCOPY	4.8
6UOA	ELECTRON MICROSCOPY	6.3
7CA5	ELECTRON MICROSCOPY	7.6
6HKC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBS5-F1	84.48	0.55

Antibody-complex structures (SAbDab): 1 — 7EB2

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 (14): 247; 247; 247; 270; 270; 270; 287; 287; 287; 367; 367; 466 …

Post-translational modifications (2): 873, 930

Disulfide bonds (4): 100–145, 131–157, 220–246, 376–410

Glycosylation sites (7): 24, 84, 409, 440, 482, 502, 514

Mutagenesis-validated functional residues (6):

Position	Phenotype
182	abolishes signaling via g-proteins. abolishes antagonist binding.
230	slightly decreases signaling via g-proteins.
234	decreases signaling via g-proteins.
287	strongly reduces signaling via g-proteins. abolishes antagonist binding.
367	strongly reduces signaling via g-proteins. no effect on antagonist binding.
395	strongly reduces signaling via g-proteins. strongly reduces antagonist binding.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1296041	Activation of G protein gated Potassium channels
R-HSA-418594	G alpha (i) signalling events
R-HSA-420499	Class C/3 (Metabotropic glutamate/pheromone receptors)
R-HSA-977444	GABA B receptor activation
R-HSA-997272	Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits

MSigDB gene sets: 432 (showing top): RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_ETHANOL, GOBP_GLUTAMATE_SECRETION, GOBP_ACID_SECRETION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_HORMONE_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY

GO Biological Process (19): osteoblast differentiation (GO:0001649), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), gamma-aminobutyric acid signaling pathway (GO:0007214), negative regulation of cell population proliferation (GO:0008285), positive regulation of glutamate secretion (GO:0014049), negative regulation of gamma-aminobutyric acid secretion (GO:0014053), negative regulation of epinephrine secretion (GO:0032811), negative regulation of dopamine secretion (GO:0033602), response to nicotine (GO:0035094), response to ethanol (GO:0045471), negative regulation of synaptic transmission (GO:0050805), synaptic transmission, GABAergic (GO:0051932), positive regulation of growth hormone secretion (GO:0060124), neuron-glial cell signaling (GO:0150099), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), regulation of glutamate secretion (GO:0014048), regulation of postsynaptic membrane potential (GO:0060078), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (8): G protein-coupled GABA receptor activity (GO:0004965), protein heterodimerization activity (GO:0046982), obsolete G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential (GO:0099579), obsolete G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential (GO:0150047), extracellular matrix protein binding (GO:1990430), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515), GABA receptor activity (GO:0016917)

GO Cellular Component (26): obsolete extracellular space (GO:0005615), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), axolemma (GO:0030673), mitochondrial membrane (GO:0031966), G protein-coupled receptor heterodimeric complex (GO:0038039), presynaptic membrane (GO:0042734), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), dendritic shaft (GO:0043198), postsynaptic membrane (GO:0045211), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), G protein-coupled GABA receptor complex (GO:1902712), extracellular region (GO:0005576), cytoplasm (GO:0005737), membrane (GO:0016020), dendrite (GO:0030425), G protein-coupled receptor dimeric complex (GO:0038037), cell projection (GO:0042995), synapse (GO:0045202), synaptic membrane (GO:0097060), presynapse (GO:0098793), GABA receptor complex (GO:1902710)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
G protein gated Potassium channels	1
GPCR downstream signalling	1
GPCR ligand binding	1
GABA receptor activation	1
Activation of GABAB receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
synapse	3
cell-cell signaling	2
GABA receptor activity	2
glutamate secretion	2
negative regulation of catecholamine secretion	2
chemical synaptic transmission	2
G protein-coupled receptor activity	2
regulation of membrane potential	2
transmembrane signaling receptor activity	2
organelle membrane	2
presynapse	2
G protein-coupled receptor dimeric complex	2
synaptic membrane	2
dendrite	2
postsynapse	2
ossification	1
cell differentiation	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of glutamate secretion	1
positive regulation of organic acid transport	1
positive regulation of amino acid transport	1
positive regulation of secretion by cell	1
gamma-aminobutyric acid secretion	1
regulation of gamma-aminobutyric acid secretion	1
negative regulation of organic acid transport	1
negative regulation of secretion	1
negative regulation of amino acid transport	1
regulation of epinephrine secretion	1
epinephrine secretion	1
dopamine secretion	1
regulation of dopamine secretion	1
response to chemical	1
response to alcohol	1
negative regulation of cell communication	1
negative regulation of signaling	1

Protein interactions and networks

STRING

1598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABBR1	GABBR2	O75899	985
GABBR1	CASR	P41180	737
GABBR1	LGI1	O95970	736
GABBR1	MPDZ	O75970	728
GABBR1	GABRB1	P18505	720
GABBR1	ATF5	Q9Y2D1	713
GABBR1	GABRA1	P14867	705
GABBR1	GABRG2	P18507	700
GABBR1	CACNA1G	O43497	695
GABBR1	GABRD	O14764	692
GABBR1	ATF7	P17544	666
GABBR1	PTP4A1	Q93096	649
GABBR1	GABRA5	P31644	641
GABBR1	GAD2	Q05329	638
GABBR1	GAD1	Q99259	629

IntAct

31 interactions, top by confidence:

A	B	Type	Score
GABBR2	GABBR1	psi-mi:“MI:0407”(direct interaction)	0.740
GABBR1	GABBR2	psi-mi:“MI:0915”(physical association)	0.740
GABBR1	NSF	psi-mi:“MI:0407”(direct interaction)	0.570
GABBR1	NSF	psi-mi:“MI:0403”(colocalization)	0.570
NSF	GABBR1	psi-mi:“MI:0915”(physical association)	0.570
GABBR1	MAX	psi-mi:“MI:0915”(physical association)	0.520
GPR37	GABBR1	psi-mi:“MI:0915”(physical association)	0.510
GABBR1	GPR37	psi-mi:“MI:0915”(physical association)	0.510
GABBR1	ABL1	psi-mi:“MI:0915”(physical association)	0.400
CRK	GABBR1	psi-mi:“MI:0915”(physical association)	0.400
GABBR1	FYN	psi-mi:“MI:0915”(physical association)	0.400
GRB2	GABBR1	psi-mi:“MI:0915”(physical association)	0.400
GABBR1	NCK1	psi-mi:“MI:0915”(physical association)	0.400
GABBR1	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
GABBR1	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
GABBR1	CCR8	psi-mi:“MI:0915”(physical association)	0.370
GABBR1	DRD2	psi-mi:“MI:0915”(physical association)	0.370
GABBR1	SMO	psi-mi:“MI:0915”(physical association)	0.370
ALB	CDC45	psi-mi:“MI:0914”(association)	0.350
GIGYF1	DYNC1I1	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
PPP1R13L	SMCHD1	psi-mi:“MI:0914”(association)	0.350
GABBR1	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
GABBR1	MAX	psi-mi:“MI:0915”(physical association)	0.000
CHFR	GABBR1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (59): Usp14 (Two-hybrid), GABBR2 (Affinity Capture-Western), USP14 (Affinity Capture-Western), DDIT3 (Affinity Capture-Western), DDIT3 (Co-localization), GABBR1 (Two-hybrid), JAKMIP1 (Affinity Capture-Western), JAKMIP1 (Reconstituted Complex), GABBR2 (Affinity Capture-Western), KCTD16 (Affinity Capture-Western), GABBR1 (Affinity Capture-Western), GABBR1 (Affinity Capture-Luminescence), GNB1 (Affinity Capture-Western), GNB1 (Affinity Capture-Luminescence), GNG2 (Affinity Capture-Luminescence)

ESM2 similar proteins: A0A1L8F5J9, A0JN27, F1LTR1, F1NBL0, O15294, P35438, P35439, P56558, P61201, P61202, P61203, P61599, P61600, P63138, P79101, P81436, Q03555, Q05586, Q13888, Q15303, Q27HV0, Q2PFM2, Q2TBV5, Q4L208, Q58ED9, Q5R1P0, Q5SP67, Q5ZJ75, Q61527, Q62956, Q6IQT4, Q6IR75, Q6P1K8, Q6P632, Q7ZXR3, Q8BUV3, Q8C6G8, Q8CGY8, Q8R4D1, Q91854

Diamond homologs: G5ECB2, O75899, O88871, Q6PCP7, Q80T41, Q8K451, Q8NFN8, Q9UBS5, Q9WV18, Q9Z0U4, H2L0Q3, O70410, P23385, P31421, P31422, P31424, P41594, P91685, P97772, Q09630, Q13255, Q14416, Q14832, Q14BI2, Q1ZZH1, Q3UVX5, Q54SW3, Q55AP3, Q5RAL3, Q5U9X3, Q9QYS2, O02839, O08569, O19124, O62685, O62837, O88174, P04003, P06681, P08174

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
CAMK2A	down-regulates	GABBR1	phosphorylation
GABBR1	“form complex”	“GABA-B receptor”	binding
CAMK2B	“down-regulates quantity by destabilization”	GABBR1	phosphorylation
ERK1/2	“down-regulates quantity by destabilization”	GABBR1	phosphorylation
MAPK3	“down-regulates quantity by destabilization”	GABBR1	phosphorylation
MAPK1	“down-regulates quantity by destabilization”	GABBR1	phosphorylation
KIF5B	“up-regulates activity”	GABBR1	relocalization
JAKMIP1	“up-regulates quantity”	GABBR1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
FCGR3A-mediated phagocytosis	5	44.6×	1e-05
Cell Cycle, Mitotic	5	11.5×	1e-03
Cell Cycle	5	8.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	7
Uncertain significance	140
Likely benign	13
Benign	3

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1804147	NM_001470.4(GABBR1):c.1190C>T (p.Ala397Val)	Likely pathogenic
1804152	NM_001470.4(GABBR1):c.1603G>A (p.Ala535Thr)	Likely pathogenic
1804153	NM_001470.4(GABBR1):c.1104G>C (p.Glu368Asp)	Likely pathogenic
1804154	NM_001470.4(GABBR1):c.2018G>A (p.Gly673Asp)	Likely pathogenic
2502369	NM_001470.4(GABBR1):c.1042G>C (p.Ala348Pro)	Likely pathogenic
3376843	NM_001470.4(GABBR1):c.2546T>C (p.Leu849Pro)	Likely pathogenic
4845651	NM_001470.4(GABBR1):c.1604C>T (p.Ala535Val)	Likely pathogenic

SpliceAI

4061 predictions. Top by Δscore:

Variant	Effect	Δscore
6:29556346:TGCAC:T	acceptor_gain	1.0000
6:29556348:CAC:C	acceptor_gain	1.0000
6:29556351:C:A	acceptor_loss	1.0000
6:29556352:T:G	acceptor_loss	1.0000
6:29604489:CGCA:C	donor_loss	1.0000
6:29604490:GCAC:G	donor_loss	1.0000
6:29604491:CA:C	donor_loss	1.0000
6:29604498:G:C	donor_gain	1.0000
6:29604510:T:A	donor_gain	1.0000
6:29604854:CCTTA:C	donor_loss	1.0000
6:29604855:CTTAC:C	donor_loss	1.0000
6:29604856:TTACC:T	donor_loss	1.0000
6:29604857:TA:T	donor_loss	1.0000
6:29604858:A:AG	donor_loss	1.0000
6:29604936:T:TA	donor_gain	1.0000
6:29604988:CCTA:C	acceptor_loss	1.0000
6:29604989:CTAG:C	acceptor_loss	1.0000
6:29605501:T:TA	donor_gain	1.0000
6:29605505:AGT:A	donor_gain	1.0000
6:29605567:A:AC	donor_gain	1.0000
6:29605567:ACTG:A	donor_gain	1.0000
6:29605568:C:CC	donor_gain	1.0000
6:29605568:CTG:C	donor_gain	1.0000
6:29605568:CTGC:C	donor_gain	1.0000
6:29606405:ATCTT:A	donor_gain	1.0000
6:29606406:T:C	donor_gain	1.0000
6:29606409:T:TA	donor_gain	1.0000
6:29606851:AGC:A	donor_gain	1.0000
6:29606881:T:TA	donor_gain	1.0000
6:29606894:TACCT:T	donor_loss	1.0000

AlphaMissense

6252 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:29604513:A:G	L898P	1.000
6:29604963:A:T	V822D	1.000
6:29604966:G:C	P821R	1.000
6:29604966:G:T	P821H	1.000
6:29605575:A:C	N811K	1.000
6:29605575:A:T	N811K	1.000
6:29605591:C:T	G806D	1.000
6:29605606:T:A	D801V	1.000
6:29605606:T:C	D801G	1.000
6:29605606:T:G	D801A	1.000
6:29605607:C:G	D801H	1.000
6:29605645:G:T	A788D	1.000
6:29605648:A:G	L787P	1.000
6:29605650:G:C	F786L	1.000
6:29605650:G:T	F786L	1.000
6:29605652:A:G	F786L	1.000
6:29605657:C:T	G784E	1.000
6:29605658:C:G	G784R	1.000
6:29605658:C:T	G784R	1.000
6:29605666:A:G	L781P	1.000
6:29605675:C:T	G778E	1.000
6:29605676:C:G	G778R	1.000
6:29605676:C:T	G778R	1.000
6:29606419:G:C	C761W	1.000
6:29606420:C:G	C761S	1.000
6:29606420:C:T	C761Y	1.000
6:29606421:A:G	C761R	1.000
6:29606421:A:T	C761S	1.000
6:29607159:C:A	K684N	1.000
6:29607159:C:G	K684N	1.000

dbSNP variants (sampled 300 via entrez): RS1000310186 (6:29606158 A>T), RS1000337210 (6:29625215 T>C), RS1000342470 (6:29614378 C>T), RS1000435898 (6:29613956 C>G,T), RS1000615469 (6:29603917 G>A), RS1000627365 (6:29626473 ACCC>A), RS1000681872 (6:29605943 C>G,T), RS1000725539 (6:29617143 A>AATGAAATT), RS1000773907 (6:29611780 A>G), RS1000932296 (6:29603669 C>A), RS1000980623 (6:29627895 C>T), RS1001011767 (6:29628397 C>G), RS1001051294 (6:29604457 C>T), RS1001156432 (6:29612009 CT>C,CTT), RS1001285274 (6:29607596 C>T)

Disease associations

OMIM: gene MIM:603540 | disease phenotypes: MIM:620502, MIM:162200

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with language delay and variable cognitive abnormalities	Strong	Autosomal dominant

Mondo (3): intellectual disability (MONDO:0001071), neurodevelopmental disorder with language delay and variable cognitive abnormalities (MONDO:0957779), neurofibromatosis type 1 (MONDO:0018975)

Orphanet (2): Neurofibromatosis type 1 (Orphanet:636), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000343	Long philtrum
HP:0000431	Wide nasal bridge
HP:0000609	Optic nerve hypoplasia
HP:0000639	Nystagmus
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0000958	Dry skin
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0002360	Sleep disturbance
HP:0002650	Scoliosis
HP:0003593	Infantile onset
HP:0004209	Clinodactyly of the 5th finger
HP:0007018	Attention deficit hyperactivity disorder
HP:0008404	Nail dystrophy
HP:0012427	Increased femoral anteversion
HP:0040183	Encopresis

GWAS associations

34 associations (top):

Study	Trait	p-value
GCST000460_3	Nasopharyngeal carcinoma	9.000000e-17
GCST001438_6	Crohn’s disease	2.000000e-10
GCST003383_1	Platelet count	1.000000e-09
GCST003880_7	Schizophrenia	5.000000e-10
GCST004294_14	Nicotine dependence	1.000000e-06
GCST004294_9	Nicotine dependence	5.000000e-06
GCST004521_112	Autism spectrum disorder or schizophrenia	3.000000e-26
GCST004521_171	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_263	Autism spectrum disorder or schizophrenia	7.000000e-17
GCST004521_268	Autism spectrum disorder or schizophrenia	7.000000e-12
GCST004521_295	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_56	Autism spectrum disorder or schizophrenia	1.000000e-22
GCST004521_58	Autism spectrum disorder or schizophrenia	1.000000e-17
GCST004521_79	Autism spectrum disorder or schizophrenia	1.000000e-16
GCST004521_80	Autism spectrum disorder or schizophrenia	1.000000e-15
GCST004610_11	White blood cell count	3.000000e-13
GCST004744_50	Lung adenocarcinoma	9.000000e-07
GCST004748_97	Lung cancer	7.000000e-19
GCST004749_82	Lung cancer in ever smokers	2.000000e-13
GCST006446_4	Ulna and radius bone mineral density	8.000000e-07
GCST008163_407	Height	2.000000e-06
GCST010142_16	Fish- and plant-related diet	2.000000e-10
GCST010142_19	Fish- and plant-related diet	4.000000e-10
GCST010142_34	Fish- and plant-related diet	7.000000e-09
GCST010142_35	Fish- and plant-related diet	8.000000e-09
GCST010142_42	Fish- and plant-related diet	1.000000e-08
GCST010142_7	Fish- and plant-related diet	3.000000e-12
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16
GCST012355_35	Depression	2.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007933	radius bone mineral density
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009456	Neurofibromatosis 1	C04.557.580.600.580.590.650; C04.700.631.650; C10.562.600.500; C10.574.500.549.400; C10.668.829.675; C16.320.400.560.400; C16.320.700.633.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2064 (SINGLE PROTEIN), CHEMBL2111463 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 186,196 (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
CHEMBL701	BACLOFEN	4	25,446
CHEMBL301742	ARBACLOFEN	3	253
CHEMBL112797	SGS-742	2	309
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1	160,188

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — GABA_B receptors

Most potent curated ligand interactions (16 total), top 16:

Ligand	Action	Affinity	Parameter
CGP 56999A	Antagonist	9.2	pIC50
CGP62349	Antagonist	9.0	pIC50
[125I]CGP71872	Antagonist	9.0	pKd
[125I]CGP64213	Antagonist	8.9	pKd
CGP 54626A	Antagonist	8.8	pIC50
CGP 64213	Antagonist	8.6	pIC50
CGP 71872	Antagonist	8.4	pIC50
lesogaberan	Agonist	8.1	pEC50
SCH50911	Antagonist	6.4	pIC50
3-APPA	Agonist	5.6	pIC50
CGP 47656	Full agonist	5.0	pIC50
CGP35348	Antagonist	4.8	pIC50
(-)-baclofen	Full agonist	4.6	pIC50
GABA	Full agonist	4.6	pIC50
2-hydroxy-saclofen	Antagonist	4.1	pIC50
saclofen	Antagonist	3.5	pIC50

Binding affinities (BindingDB)

4 measured of 9 human assays (9 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL237582	EC50	2750 nM
CHEMBL401437	EC50	3470 nM
CHEMBL2322934	EC50	37800 nM
CHEMBL2322935	EC50	40000 nM

ChEMBL bioactivities

71 potent at pChembl≥5 of 89 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	CHEMBL4763515
9.00	Kd	1	nM	CHEMBL1628548
8.92	IC50	1.2	nM	CHEMBL4791366
8.62	IC50	2.4	nM	CHEMBL4756657
8.62	IC50	2.4	nM	CHEMBL112203
8.54	Ki	2.9	nM	CHEMBL2391908
8.31	IC50	4.9	nM	CHEMBL4787614
8.19	IC50	6.4	nM	CHEMBL2391908
8.18	IC50	6.6	nM	CHEMBL112710
8.07	EC50	8.6	nM	CHEMBL3600560
7.89	IC50	13	nM	CHEMBL4847170
7.82	IC50	15	nM	ARBACLOFEN
7.75	IC50	18	nM	CHEMBL113453
7.73	IC50	18.6	nM	CHEMBL4745449
7.72	IC50	18.9	nM	CHEMBL4762233
7.68	IC50	21	nM	CHEMBL4856595
7.63	IC50	23.2	nM	CHEMBL4740566
7.60	IC50	25	nM	GAMMA-AMINOBUTYRIC ACID
7.54	IC50	29	nM	CHEMBL113304
7.46	IC50	35	nM	BACLOFEN
7.41	IC50	39	nM	CHEMBL430501
7.30	IC50	50	nM	BACLOFEN
7.19	EC50	64	nM	CHEMBL5207265
7.10	EC50	79.43	nM	GS-39783
7.05	EC50	90	nM	CHEMBL5170235
7.01	EC50	97	nM	CHEMBL5185974
6.85	EC50	142	nM	CHEMBL5204436
6.78	IC50	166	nM	CHEMBL113396
6.70	IC50	200	nM	CHEMBL312675
6.70	EC50	199	nM	CHEMBL5169533
6.70	EC50	200	nM	CHEMBL112710
6.68	EC50	208	nM	CHEMBL5183971
6.55	IC50	280	nM	CHEMBL113217
6.53	EC50	294	nM	CHEMBL5187574
6.47	EC50	341	nM	CHEMBL5193733
6.44	IC50	360	nM	CHEMBL111378
6.38	EC50	419	nM	CHEMBL5188066
6.35	EC50	444	nM	CHEMBL5202253
6.30	EC50	496	nM	CHEMBL5186902
6.30	IC50	500	nM	CHEMBL113907
6.28	EC50	530	nM	GAMMA-AMINOBUTYRIC ACID
6.21	IC50	610	nM	4-AMINO-3- (5-CHLOROTHIEN-2-YL)BUTANOIC ACID
6.20	EC50	637	nM	CHEMBL5209256
6.13	EC50	741.3	nM	GS-39783
6.12	EC50	764	nM	CHEMBL2346820
6.11	EC50	771	nM	CHEMBL5209395
6.11	IC50	780	nM	CHEMBL111920
6.06	IC50	880	nM	CHEMBL109752
6.06	EC50	871	nM	CHEMBL393066
6.04	IC50	920	nM	CHEMBL111675

PubChem BioAssay actives

67 with measured affinity, of 439 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
(4S)-5-[[(2S,3S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-benzamidoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoic acid	1687077: Activation of human GABAB1/GABAB2 expressed in HEK293 cells co-transfected with rat CaV2.2 channel assessed as reduction in CaV2.2-mediated peak-current amplitude in response to the depolarizing pulse by whole cell patch clamp assay	ic50	0.0002	uM
3-(1R)-1-[[(2S)-3-[5-[(4-azido-2-hydroxy-5-(125I)iodobenzoyl)amino]pentyl-hydroxyphosphoryl]-2-hydroxypropyl]amino]ethylbenzoic acid	1237980: Binding affinity to GABA-B receptor (unknown origin)	kd	0.0010	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-benzamidoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-oxobutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S,3S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1687077: Activation of human GABAB1/GABAB2 expressed in HEK293 cells co-transfected with rat CaV2.2 channel assessed as reduction in CaV2.2-mediated peak-current amplitude in response to the depolarizing pulse by whole cell patch clamp assay	ic50	0.0012	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-oxobutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S,3S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1687077: Activation of human GABAB1/GABAB2 expressed in HEK293 cells co-transfected with rat CaV2.2 channel assessed as reduction in CaV2.2-mediated peak-current amplitude in response to the depolarizing pulse by whole cell patch clamp assay	ic50	0.0024	uM
3-aminopropyl-hydroxy-oxophosphanium	71258: Inhibition of [3H]-baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.0024	uM
cyclohexylmethyl-[(2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino]-2-hydroxypropyl]phosphinic acid;hydrochloride	751678: Displacement of [3H]CGP54626 from human recombinant GABAB1A receptor expressed in CHO cells after 3 hrs	ki	0.0029	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S,3S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1687077: Activation of human GABAB1/GABAB2 expressed in HEK293 cells co-transfected with rat CaV2.2 channel assessed as reduction in CaV2.2-mediated peak-current amplitude in response to the depolarizing pulse by whole cell patch clamp assay	ic50	0.0049	uM
3-aminopropyl(methyl)phosphinic acid	71258: Inhibition of [3H]-baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.0066	uM
[(2R)-3-amino-2-fluoropropyl]phosphonic acid	1237985: Agonist activity at human recombinant GABA-B receptor	ec50	0.0086	uM
3-[(1S,6R,9S,12S,15S,21S,24S,27S,30S,33S,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-30-(2-amino-2-oxoethyl)-9-[(2S)-butan-2-yl]-36-(3-carbamimidamidopropyl)-6-carbamoyl-24,45-bis(carboxymethyl)-48-(hydroxymethyl)-27-[(4-hydroxyphenyl)methyl]-21-(1H-imidazol-5-ylmethyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-3,4-dithia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacont-55-yn-12-yl]propanoic acid	1762195: Agonist activity at human GABAB expressed in HEK293T cells co-transfected with human CaV2.2 channel assessed as inhibition of CaV2.2-mediated Ba2+ peak-current amplitude at -80 to 10 mV holding potential after 72 hrs by whole cell patch clamp assay	ic50	0.0130	uM
(3R)-4-amino-3-(4-chlorophenyl)butanoic acid	71258: Inhibition of [3H]-baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.0150	uM
(3-amino-2-hydroxypropyl)-hydroxy-oxophosphanium	71258: Inhibition of [3H]-baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.0180	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S,3S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1687077: Activation of human GABAB1/GABAB2 expressed in HEK293 cells co-transfected with rat CaV2.2 channel assessed as reduction in CaV2.2-mediated peak-current amplitude in response to the depolarizing pulse by whole cell patch clamp assay	ic50	0.0186	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-acetamidoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S,3S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1687077: Activation of human GABAB1/GABAB2 expressed in HEK293 cells co-transfected with rat CaV2.2 channel assessed as reduction in CaV2.2-mediated peak-current amplitude in response to the depolarizing pulse by whole cell patch clamp assay	ic50	0.0189	uM
3-[(1R,4S,7S,10S,13S,19S,22S,25S,28R,33R,36R,39S,42S,48S,51S)-33-[(2-aminoacetyl)amino]-4-(2-amino-2-oxoethyl)-25-[(2S)-butan-2-yl]-51-(3-carbamimidamidopropyl)-28-carbamoyl-10,42-bis(carboxymethyl)-39-(hydroxymethyl)-7-[(4-hydroxyphenyl)methyl]-13-(1H-imidazol-5-ylmethyl)-2,5,8,11,14,20,23,26,34,37,40,43,49,52-tetradecaoxo-30,31,55,56-tetrathia-3,6,9,12,15,21,24,27,35,38,41,44,50,53-tetradecazatetracyclo[34.17.4.015,19.044,48]heptapentacontan-22-yl]propanoic acid	1762195: Agonist activity at human GABAB expressed in HEK293T cells co-transfected with human CaV2.2 channel assessed as inhibition of CaV2.2-mediated Ba2+ peak-current amplitude at -80 to 10 mV holding potential after 72 hrs by whole cell patch clamp assay	ic50	0.0210	uM
(4S)-5-[[(2S,3S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-amino-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoic acid	1687077: Activation of human GABAB1/GABAB2 expressed in HEK293 cells co-transfected with rat CaV2.2 channel assessed as reduction in CaV2.2-mediated peak-current amplitude in response to the depolarizing pulse by whole cell patch clamp assay	ic50	0.0232	uM
.gamma.-aminobutyric acid	71258: Inhibition of [3H]-baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.0250	uM
(3-amino-2-hydroxypropyl)-methylphosphinic acid	71256: Inhibition of [3H]CGP-27492 binding to cat Gamma-aminobutyric acid type B receptor	ic50	0.0290	uM
Baclofen	71258: Inhibition of [3H]-baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.0350	uM
[3-amino-2-(4-chlorophenyl)propyl]-hydroxy-oxophosphanium	71257: Inhibition of [3H]baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.0390	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-2-chloro-6-(3,5-dichlorophenyl)quinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.0640	uM
4-N,6-N-dicyclopentyl-2-methylsulfanyl-5-nitropyrimidine-4,6-diamine	1474762: Positive allosteric modulation at human GABA-B 1b expressed in CHO cells co-expressing rat GABA-B2 assessed as potentiation of GABA-induced inhibition of 7beta forskolin-stimulated cyclic AMP formation after 2 hrs in presence of 0.3 uM GABA relative to 100 uM GABA alone	ec50	0.0794	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-2-chloro-6-[3-(trifluoromethyl)phenyl]quinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.0900	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-6-(3,5-dichlorophenyl)-2-methylquinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.0970	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-2-methyl-6-[3-(trifluoromethyl)phenyl]quinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.1420	uM
4-aminobutan-2-yl(methyl)phosphinic acid	71256: Inhibition of [3H]CGP-27492 binding to cat Gamma-aminobutyric acid type B receptor	ic50	0.1660	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-6-(3-chlorophenyl)-2-methylquinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.1990	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-2-chloro-6-(4-chlorophenyl)quinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.2080	uM
[(E)-3-aminoprop-1-enyl]-hydroxy-oxophosphanium	71258: Inhibition of [3H]-baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.2800	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-2-chloro-6-(4-fluorophenyl)quinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.2940	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-2-chloro-6-(3,4-dichlorophenyl)quinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.3410	uM
[3-amino-2-(4-fluorophenyl)propyl]-hydroxy-oxophosphanium	71257: Inhibition of [3H]baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.3600	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-6-(3,4-dichlorophenyl)-2-methylquinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.4190	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-6-(4-chlorophenyl)-2-methylquinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.4440	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-6-(2-chlorophenyl)-2-methylquinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.4960	uM
3-aminobutyl-hydroxy-oxophosphanium	71258: Inhibition of [3H]-baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.5000	uM
4-amino-3-(5-chlorothiophen-2-yl)butanoic acid	1237980: Binding affinity to GABA-B receptor (unknown origin)	ic50	0.6100	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-2-chloro-6-[4-(trifluoromethyl)phenyl]quinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.6370	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-2-methyl-5-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.7640	uM
N-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-2-methyl-6-[4-(trifluoromethyl)phenyl]quinazolin-4-amine	1867062: Positive allosteric modulation of GABA-B receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding by [35S]GTPgammaS binding assay	ec50	0.7710	uM
(3-amino-2-methylpropyl)-hydroxy-oxophosphanium	71258: Inhibition of [3H]-baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.7800	uM
N-cyclohexyl-2-methyl-5-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine	301941: Activity at GABAB 1b/2 receptor expressed in CHO-K1 cells assessed as effect on glutamate-induced [35S]GTP-gamma-S binding	ec50	0.8710	uM
(3-amino-2-phenylpropyl)-hydroxy-oxophosphanium	71257: Inhibition of [3H]baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.8800	uM
4-aminobutan-2-yl-hydroxy-oxophosphanium	71258: Inhibition of [3H]-baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	0.9200	uM
4-[[(1S,2R,4R)-2-bicyclo[2.2.1]heptanyl]amino]-5-[4-(trifluoromethyl)phenyl]pyrimidine-2-carbonitrile	301941: Activity at GABAB 1b/2 receptor expressed in CHO-K1 cells assessed as effect on glutamate-induced [35S]GTP-gamma-S binding	ec50	1.2023	uM
3-aminopropyl(ethyl)phosphinic acid	71258: Inhibition of [3H]-baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	1.3500	uM
N-[(1S,2R,4R)-2-bicyclo[2.2.1]heptanyl]-2-methyl-5-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine	301941: Activity at GABAB 1b/2 receptor expressed in CHO-K1 cells assessed as effect on glutamate-induced [35S]GTP-gamma-S binding	ec50	1.6596	uM
N-cycloheptyl-2-methyl-5-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine	301941: Activity at GABAB 1b/2 receptor expressed in CHO-K1 cells assessed as effect on glutamate-induced [35S]GTP-gamma-S binding	ec50	1.6596	uM
4-N-[(1S,2R,4R)-2-bicyclo[2.2.1]heptanyl]-2-N,2-N-dimethyl-5-[4-(trifluoromethyl)phenyl]pyrimidine-2,4-diamine	301941: Activity at GABAB 1b/2 receptor expressed in CHO-K1 cells assessed as effect on glutamate-induced [35S]GTP-gamma-S binding	ec50	1.6596	uM
(3S)-4-amino-3-(4-chlorophenyl)butanoic acid	71258: Inhibition of [3H]-baclofen binding to Gamma-aminobutyric acid type B receptor of cat cerebellum	ic50	1.7700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
gamma-Aminobutyric Acid	affects binding, increases activity, increases reaction, decreases reaction	3
Valproic Acid	affects expression, increases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Arsenic	increases expression, affects methylation, increases abundance	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	affects cotreatment, decreases methylation	1
arsenite	affects binding, decreases reaction	1
3-aminopropylphosphinic acid	increases activity, increases reaction, affects binding	1
tribromoethanol	increases activity, increases reaction	1
di-n-butylphosphoric acid	affects expression	1
CGP 55845A	decreases activity, affects binding, decreases reaction, increases activity, increases reaction	1
CGP 71872	affects binding, decreases reaction, increases activity	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol	increases reaction, decreases reaction, affects binding, increases activity	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
jinfukang	increases expression	1
picoxystrobin	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sevoflurane	decreases reaction, increases activity	1
Gabapentin	decreases reaction, increases activity, affects binding	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

94 unique, capped per target: 71 binding, 22 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2167243	Binding	Inhibition of human GABAB1A receptor at 10 uM by radioligand displacement assay	ADME-guided design and synthesis of aryloxanyl pyrazolone derivatives to block mutant superoxide dismutase 1 (SOD1) cytotoxicity and protein aggregation: potential application for the treatment of amyotrophic lateral sclerosis. — J Med Chem
CHEMBL964516	Functional	Agonist activity at human GABAb 1A/2 receptor expressed in Xenopus oocytes assessed as whole cell current production by two electrode voltage clamp method	Novel gamma-aminobutyric acid rho1 receptor antagonists; synthesis, pharmacological activity and structure-activity relationships. — J Med Chem
CHEMBL4810231	ADMET	Inhibition of GABA-B 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

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 2 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1SM	Abcam U-87MG GABBR1 KO	Cancer cell line	Male
CVCL_D7QF	Ubigene A-549 GABBR1 KO	Cancer cell line	Male
CVCL_D8LR	Ubigene HCT 116 GABBR1 KO	Cancer cell line	Male
CVCL_D9FA	Ubigene HEK293 GABBR1 KO	Transformed cell line	Female
CVCL_E0DL	Ubigene HeLa GABBR1 KO	Cancer cell line	Female
CVCL_KV19	cAMP Hunter CHO-K1 GABBR1-GABBR2 Gi	Spontaneously immortalized cell line	Female
CVCL_LC01	CHO-K1 h-GABA-b R1a/R2	Spontaneously immortalized cell line	Female
CVCL_SP41	HAP1 GABBR1 (-) 1	Cancer cell line	Male
CVCL_SP42	HAP1 GABBR1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
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