GNB1

Summary

GNB1 (G protein subunit beta 1, HGNC:4396) is a protein-coding gene on chromosome 1p36.33, encoding Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (P62873). Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems.

Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2782 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, autosomal dominant 42 (Definitive, ClinGen)
• GWAS associations: 5
• Clinical variants (ClinVar): 399 total — 28 pathogenic, 18 likely-pathogenic
• Phenotypes (HPO): 90
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002074

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4396
Approved symbol	GNB1
Name	G protein subunit beta 1
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000078369
Ensembl biotype	protein_coding
OMIM	139380
Entrez	2782

Gene structure

Transcript identifiers

Ensembl transcripts: 115 — 108 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000378609, ENST00000434686, ENST00000437146, ENST00000439272, ENST00000461893, ENST00000471354, ENST00000472614, ENST00000607589, ENST00000610897, ENST00000615252, ENST00000703692, ENST00000703693, ENST00000703694, ENST00000703695, ENST00000703696, ENST00000703697, ENST00000703698, ENST00000703699, ENST00000703700, ENST00000703701, ENST00000703702, ENST00000703703, ENST00000703704, ENST00000703705, ENST00000703706, ENST00000703707, ENST00000703708, ENST00000703709, ENST00000703710, ENST00000703711, ENST00000703712, ENST00000899366, ENST00000899367, ENST00000899368, ENST00000899369, ENST00000899370, ENST00000899371, ENST00000899372, ENST00000899373, ENST00000899374, ENST00000899375, ENST00000899376, ENST00000899377, ENST00000899378, ENST00000899379, ENST00000899380, ENST00000899381, ENST00000899382, ENST00000899383, ENST00000899384, ENST00000899385, ENST00000899386, ENST00000899387, ENST00000899388, ENST00000899389, ENST00000916682, ENST00000916683, ENST00000916684, ENST00000916685, ENST00000916686, ENST00000916687, ENST00000916688, ENST00000916689, ENST00000916690, ENST00000916691, ENST00000916692, ENST00000916693, ENST00000916694, ENST00000916695, ENST00000916696, ENST00000916697, ENST00000916698, ENST00000916699, ENST00000916700, ENST00000916701, ENST00000916702, ENST00000916703, ENST00000916704, ENST00000916705, ENST00000916706, ENST00000916707, ENST00000916708, ENST00000916709, ENST00000916710, ENST00000916711, ENST00000916712, ENST00000916713, ENST00000916714, ENST00000916715, ENST00000947516, ENST00000947517, ENST00000947518, ENST00000947519, ENST00000947520, ENST00000947521, ENST00000947522, ENST00000947523, ENST00000947524, ENST00000947525, ENST00000947526, ENST00000947527, ENST00000947528, ENST00000947529, ENST00000947530, ENST00000947531, ENST00000947532, ENST00000947533, ENST00000947534, ENST00000947535, ENST00000947536, ENST00000947537, ENST00000947538, ENST00000947539, ENST00000947540, ENST00000947541

RefSeq mRNA: 3 — MANE Select: NM_002074 NM_001282538, NM_001282539, NM_002074

CCDS: CCDS34, CCDS72685

Canonical transcript exons

ENST00000378609 — 12 exons

Exon	Start	End
ENSE00001066529	1817837	1817875
ENSE00001356799	1839190	1839238
ENSE00001370751	1890820	1891087
ENSE00001717648	1789053	1789269
ENSE00001728156	1787322	1787437
ENSE00001809357	1785286	1787053
ENSE00003268669	1825397	1825499
ENSE00003465100	1815756	1815862
ENSE00003609842	1804419	1804581
ENSE00003629446	1806475	1806538
ENSE00003676440	1790395	1790596
ENSE00003791115	1793245	1793311

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 173.7988 / max 2379.9696, expressed in 1827 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9854	168.1851	1827
9853	2.8169	1393
9833	0.8440	445
9843	0.7858	533
9846	0.3286	113
9840	0.2107	76
9847	0.1829	6
9841	0.1699	52
9842	0.1492	34
9848	0.0837	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.60	gold quality
ganglionic eminence	UBERON:0004023	99.47	gold quality
secondary oocyte	CL:0000655	99.42	gold quality
prefrontal cortex	UBERON:0000451	99.42	gold quality
CA1 field of hippocampus	UBERON:0003881	99.41	gold quality
orbitofrontal cortex	UBERON:0004167	99.39	gold quality
stromal cell of endometrium	CL:0002255	99.36	gold quality
superior vestibular nucleus	UBERON:0007227	99.36	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.33	gold quality
parietal lobe	UBERON:0001872	99.29	gold quality
caput epididymis	UBERON:0004358	99.29	gold quality
frontal cortex	UBERON:0001870	99.27	gold quality
ventricular zone	UBERON:0003053	99.26	gold quality
postcentral gyrus	UBERON:0002581	99.25	gold quality
corpus epididymis	UBERON:0004359	99.25	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.24	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.24	gold quality
pons	UBERON:0000988	99.23	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.22	gold quality
neocortex	UBERON:0001950	99.21	gold quality
superior frontal gyrus	UBERON:0002661	99.21	gold quality
right frontal lobe	UBERON:0002810	99.20	gold quality
entorhinal cortex	UBERON:0002728	99.19	gold quality
substantia nigra pars compacta	UBERON:0001965	99.18	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.15	gold quality
cerebral cortex	UBERON:0000956	99.14	gold quality
cauda epididymis	UBERON:0004360	99.13	gold quality
trigeminal ganglion	UBERON:0001675	99.11	gold quality
medulla oblongata	UBERON:0001896	99.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	2945.75
E-MTAB-7316	yes	72.49
E-HCAD-13	yes	7.00
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, ESR2

miRNA regulators (miRDB)

86 targeting GNB1, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-664B-3P	99.84	71.65	3590

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Directional sensing requires GNB1-mediated PAK1 and PIX alpha-dependent activation of Cdc42. (PMID:12887923)
• Data show that G protein inhibition of N-type calcium channels is critically dependent on two separate but adjacent approximately 20-amino acid regions of the Gbeta subunit, as examined with Gbetas 1 and 5 and Ggamma2. (PMID:15105422)
• in elderly subjects of similar ages, those with diabetes have 1.7-fold higher levels of Galpha(i2) and twofold higher levels of Gbeta(1). (PMID:15331550)
• G betagamma binds HDAC5 and inhibits its transcriptional co-repression activity (PMID:16221676)
• HSD-3.8 (SPAG1), interacts with G-protein beta 1 subunit and activates extracellular signal-regulated kinases 1 and 2 (PMID:16368546)
• Gialpha and Gbeta subunits both define selectivity of G protein activation by alpha2-adrenergic receptors. (PMID:16371464)
• G protein betagamma subunits stimulate type V and VI adenylyl cyclases (PMID:17110384)
• No likely pathogenic GNB1 mutations have been found in any of 185 unrelated patients with autosomal dominant retinitis pigmentosa. (PMID:17167406)
• While digenic disease with the SP4 Asn306Ser and the GNB1 intronic variant alleles has not been established, neither has it been ruled out. This leaves open the possibility of a cooperative involvement of SP4 and GNB1 in the normal function of the retina. (PMID:17356515)
• Fission of transport carriers at the trans-Golgi network is dependent on specifically PLCbeta3, which is necessary to activate PKCeta and PKD in that Golgi compartment, via diacylglycerol production. (PMID:17492941)
• Gbetagamma mediates UVB-induced human keratinocyte apoptosis by augmenting the ectodomain shedding of HB-EGF, which sequentially activates EGFR and p38 (PMID:17548351)
• signaling pathway by which G(i)-coupled receptor specifically induces Rac and Cdc42 activation through direct interaction of Gbetagamma with FLJ00018. (PMID:18045877)
• RACK1 regulates directional cell migration by acting on G betagamma at the interface with its effectors PLC beta and PI3K gamma (PMID:18596232)
• Results identify novel functions of beta-arrestin1 in binding to the beta1gamma2 subunits of heterotrimeric G-proteins and promoting G(betagamma)-mediated Akt signalling for NF-kappaB activation. (PMID:18729826)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• Strong candidate gene for severe retinitis pigmentosa, RP32 (human 1p34.3-p13.3). Conclusion is based on a massive expression data set for mouse (103 strains) and joint analysis of RetNet database. (PMID:19727342)
• Gbeta1-mediated Fyn activation integrates FAK with AJ, preventing persistent endothelial barrier leakiness. (PMID:19917775)
• Data show that activation of PLCbeta(2) by alpha(q) and beta1gamma2 differ from activation by Rac2 and from each other. (PMID:20007712)
• Gbetagamma subunits enter in a protein complex with activated Rap1a and its effector Radil; this complex is required downstream of receptor stimulation for the activation of integrins and the positive modulation of cell-matrix adhesiveness. (PMID:20048162)
• Data implicate the domain I-II linker region as an important contributor to voltage dependent Gbeta1/Ggamma2 modulation of Cav2.2 calcium channels. (PMID:20181083)
• This protein has been found differentially expressed in the anterior cingulate cortex from patients with schizophrenia (PMID:20381070)
• Gbetagamma inhibits Epac-induced Ca 2+ elevation in melanoma cells. Cross talk of Ca 2+ signaling between Gbetagamma & Epac plays a major role in melanoma cell migration. (PMID:21679469)
• WDR26 is a novel Gbetagamma-binding protein that is required for the efficacy of Gbetagamma signaling and leukocyte migration (PMID:22065575)
• This study provided evidence that GNB1 gene polymorphisms are related to rapid virological response in HCV-1 and HCV-2 infected patients. GNB1 may play an important role in activating the antiviral response prior to treatment. (PMID:23171003)
• Findings suggest a wide-ranging mechanism by which direct interaction of Gbetagamma with specific chromatin bound transcription factors regulates functional gene networks in response to GPCR activation in cells including the angiotensin II type 1 receptor. (PMID:23326349)
• GNB1 plays an important role in the mTOR-related anti-apoptosis pathway and can potentially be targeted in the treatment of human breast cancer. (PMID:23603342)
• During corticogenesis, a cilium-transduced, noncanonical IGF-1R-Gbetagamma-phospho(T94)Tctex-1 signaling pathway promotes the proliferation of neural progenitors through modulation of ciliary resorption and G1 length. (PMID:23954591)
• Data indicate that endogenous mTOR interacts with Gbetagamma. (PMID:24462769)
• GNB1 and GNB2 alterations confer transformed and resistance phenotypes across a range of human tumors and may be targetable with inhibitors of G protein signaling. (PMID:25485910)
• PhLP1 binding stabilizes the Gbeta fold, disrupting interactions with CCT and releasing a PhLP1-Gbeta dimer for assembly with Ggamma. (PMID:25675501)
• Germline De Novo Mutations in GNB1 Cause Severe Neurodevelopmental Disability, Hypotonia, and Seizures. (PMID:27108799)
• we demonstrate a pathogenic role of de novo and autosomal dominant mutations in GNB1 as a cause of Global developmental delay and provide insights how perturbation in heterotrimeric G protein function contributes to the disease (PMID:28087732)
• Through analysis of the genomic and proteomic profiles of resistant cells, we identified an acquired mutation in the GNB1 gene, K89M, as the most likely cause of the resistance (PMID:28650474)
• Mutation in the GNB1 gene is associated with neurodevelopmental disorder and cutaneous mastocytosis. (PMID:29174093)
• In the new cohort of 18 patients, 50% of males had genitourinary anomalies and 61% of patients had gastrointestinal anomalies, suggesting a possible association of these findings with variants in GNB1. (PMID:30194818)
• Genotype-phenotype correlation in GNB1-related neurodevelopmental disorder: Potential association of p.Leu95Pro with cleft palate. (PMID:33427398)
• Gbetagamma translocation to the Golgi apparatus activates ARF1 to spatiotemporally regulate G protein-coupled receptor signaling to MAPK. (PMID:34022220)
• Shikonin induces cell autophagy via modulating the microRNA -545-3p/guanine nucleotide binding protein beta polypeptide 1 axis, thereby disrupting cellular carcinogenesis in colon cancer. (PMID:35192430)
• AFAP1 antisense RNA 1 promotes retinoblastoma progression by sponging microRNA miR-545-3p that targets G protein subunit beta 1. (PMID:35193469)
• G Protein Subunit beta1 Facilitates Influenza A Virus Replication by Promoting the Nuclear Import of PB2. (PMID:35604143)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gnb1b	ENSDARG00000104372
mus_musculus	Gnb1	ENSMUSG00000029064
rattus_norvegicus	Gnb1	ENSRNOG00000016638
rattus_norvegicus		ENSRNOG00000066938
drosophila_melanogaster	Gbeta13F	FBGN0001105
caenorhabditis_elegans		WBGENE00001679

Paralogs (4): GNB5 (ENSG00000069966), GNB3 (ENSG00000111664), GNB4 (ENSG00000114450), GNB2 (ENSG00000172354)

Protein

Protein identifiers

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 — P62873 (reviewed: P62873)

Alternative names: Transducin beta chain 1

All UniProt accessions (8): P62873, A0A140VJJ8, A0A994J3T6, A0A994J6X8, B1AKQ8, B3KVK2, F6UT28, F6X3N5

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.

Subunit / interactions. G proteins are composed of 3 units, alpha, beta and gamma. The heterodimer formed by GNB1 and GNG2 interacts with ARHGEF5. The heterodimer formed by GNB1 and GNG2 interacts with GRK2. The heterodimer formed by GNB1 and GNG2 interacts with the ghrelin receptor GHSR. Forms a complex with GNAO1 and GNG3. Interacts with ARHGEF18 and RASD2. Forms complexes with TAS2R14 and G-proteins; these complexes play a role in the perception of bitterness. Component of the TAS2R14-GNAI1 complex, consisting of TAS2R14, GNAI1, GNB1 and GNG2. Component of the TAS2R14-GNAT3 complex, consisting of TAS2R14, GNAT3, GNB1 and GNG2. Component of the TAS2R14-GNAS2 complex, consisting of TAS2R14, GNAS2, GNB1 and GNG2. Component of the ADORA1-GNAI2 complex, consisting of ADORA1, GNAI2, GNB1 and GNG2. Component of the CNR1-GNAI2 complex, consisting of CNR1, GNAI2, GNB1 and GNG2. Component of the FPR2-GNAI2 complex, consisting of FPR2, GNAI2, GNB1 and GNG2. Interacts with MC1R, the interaction is important for coupling of MC1R to G protein. Component of a complex composed of FPR1 or FPR2 receptor and G(i) protein subunits GNAI1, GNB1 and GNG2; this complex is involved in innate recognition of N-formyl-methionyl peptides derived from invading microbes and host mitochondria as pathogen- and damage-associated molecular patterns (PAMPs and DAMPs).

Post-translational modifications. Phosphorylation at His-266 by NDKB contributes to G protein activation by increasing the high energetic phosphate transfer onto GDP.

Disease relevance. Intellectual developmental disorder, autosomal dominant 42 (MRD42) [MIM:616973] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD42 patients manifest global developmental delay commonly accompanied by hypotonia, seizures of various types, ophthalmological manifestations, and poor growth. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the WD repeat G protein beta family.

Isoforms (2)

UniProt ID	Names	Canonical?
P62873-1	1	yes
P62873-2	2

RefSeq proteins (3): NP_001269467, NP_001269468, NP_002065* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001632	WD40_G-protein_beta-like	Domain
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016346	G-protein_beta_1-5	Family
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF25391

UniProt features (80 total): strand 34, sequence variant 19, turn 11, repeat 7, modified residue 3, helix 3, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

1262 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8QEH	X-RAY DIFFRACTION	1.43
8QEG	X-RAY DIFFRACTION	1.7
8F0K	ELECTRON MICROSCOPY	1.9
9YDQ	ELECTRON MICROSCOPY	1.94
9YDP	ELECTRON MICROSCOPY	1.95
6CRK	X-RAY DIFFRACTION	2
8F0J	ELECTRON MICROSCOPY	2
8F2B	ELECTRON MICROSCOPY	2
9XXT	ELECTRON MICROSCOPY	2
6X18	ELECTRON MICROSCOPY	2.1
6X19	ELECTRON MICROSCOPY	2.1
9P7Z	ELECTRON MICROSCOPY	2.1
7RTB	ELECTRON MICROSCOPY	2.14
9YDR	ELECTRON MICROSCOPY	2.14
5UKL	X-RAY DIFFRACTION	2.15
7TYF	ELECTRON MICROSCOPY	2.2
8F2A	ELECTRON MICROSCOPY	2.2
9BP3	ELECTRON MICROSCOPY	2.2
9MZE	ELECTRON MICROSCOPY	2.2
9N05	ELECTRON MICROSCOPY	2.2
9VAW	ELECTRON MICROSCOPY	2.24
6UVA	ELECTRON MICROSCOPY	2.3
6WZG	ELECTRON MICROSCOPY	2.3
8E3X	ELECTRON MICROSCOPY	2.3
8E3Y	ELECTRON MICROSCOPY	2.3
8YN9	ELECTRON MICROSCOPY	2.3
9BUB	ELECTRON MICROSCOPY	2.3
9HYI	ELECTRON MICROSCOPY	2.3
9N0E	ELECTRON MICROSCOPY	2.3
9O36	ELECTRON MICROSCOPY	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62873-F1	97.04	0.97

Antibody-complex structures (SAbDab): 803 — 5UZ7, 6B3J, 6CRK, 6DDE, 6E3Y, 6GDG, 6KPF, 6KPG, 6LFM, 6LFO, 6LI3, 6LMK, 6LML, 6M1H, 6M1I, 6N4B, 6NI3, 6NIY, 6OIJ, 6OIK, 6OMM, 6OS9, 6OT0, 6P9X, 6P9Y (+778 more)

Functional residue map

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

Post-translational modifications (3): 2, 266, 2

Function

Pathways and Gene Ontology

Reactome pathways

34 pathways

ID	Pathway
R-HSA-1296041	Activation of G protein gated Potassium channels
R-HSA-163359	Glucagon signaling in metabolic regulation
R-HSA-202040	G-protein activation
R-HSA-2485179	Activation of the phototransduction cascade
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-381676	Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-381753	Olfactory Signaling Pathway
R-HSA-381771	Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-HSA-392170	ADP signalling through P2Y purinoceptor 12
R-HSA-392451	G beta:gamma signalling through PI3Kgamma
R-HSA-392851	Prostacyclin signalling through prostacyclin receptor
R-HSA-400042	Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-4086398	Ca2+ pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-418217	G beta:gamma signalling through PLC beta
R-HSA-418555	G alpha (s) signalling events
R-HSA-418592	ADP signalling through P2Y purinoceptor 1
R-HSA-418594	G alpha (i) signalling events
R-HSA-418597	G alpha (z) signalling events
R-HSA-420092	Glucagon-type ligand receptors
R-HSA-428930	Thromboxane signalling through TP receptor
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-500657	Presynaptic function of Kainate receptors
R-HSA-6814122	Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
R-HSA-8964315	G beta:gamma signalling through BTK
R-HSA-8964616	G beta:gamma signalling through CDC42
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9634597	GPER1 signaling

MSigDB gene sets: 549 (showing top): MORF_DNMT1, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS, MORF_ESPL1, GOBP_RESPONSE_TO_PROSTAGLANDIN_E, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_ADRENALINE_NORADRENALINE_INHIBITS_INSULIN_SECRETION, GOCC_VACUOLAR_MEMBRANE, REACTOME_POTASSIUM_CHANNELS, YANG_BREAST_CANCER_ESR1_BULK_UP, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, GOBP_CELLULAR_RESPONSE_TO_PROSTAGLANDIN_STIMULUS, MORF_RRM1

GO Biological Process (11): signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating dopamine receptor signaling pathway (GO:0007191), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), G protein-coupled acetylcholine receptor signaling pathway (GO:0007213), Ras protein signal transduction (GO:0007265), cell population proliferation (GO:0008283), sensory perception of taste (GO:0050909), retina development in camera-type eye (GO:0060041), cellular response to prostaglandin E stimulus (GO:0071380), cellular response to catecholamine stimulus (GO:0071870)

GO Molecular Function (5): GTPase activity (GO:0003924), signaling receptor complex adaptor activity (GO:0030159), protein-containing complex binding (GO:0044877), GTPase binding (GO:0051020), protein binding (GO:0005515)

GO Cellular Component (11): cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), cytosol (GO:0005829), heterotrimeric G-protein complex (GO:0005834), plasma membrane (GO:0005886), membrane (GO:0016020), synapse (GO:0045202), extracellular exosome (GO:0070062), photoreceptor disc membrane (GO:0097381), extracellular vesicle (GO:1903561), photoreceptor outer segment (GO:0001750)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
GPCR downstream signalling	5
The phototransduction cascade	2
Regulation of insulin secretion	2
Signal amplification	2
G-protein beta:gamma signalling	2
G protein gated Potassium channels	1
Integration of energy metabolism	1
Opioid Signalling	1
Sensory Perception	1
Incretin synthesis, secretion, and inactivation	1
Platelet homeostasis	1
Beta-catenin independent WNT signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular process	2
G protein-coupled receptor signaling pathway	2
binding	2
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
G protein-coupled dopamine receptor signaling pathway	1
phospholipase C activator activity	1
G protein-coupled acetylcholine receptor activity	1
acetylcholine receptor signaling pathway	1
small GTPase-mediated signal transduction	1
sensory perception of chemical stimulus	1
camera-type eye development	1
anatomical structure development	1
response to prostaglandin E	1
cellular response to prostaglandin stimulus	1
cellular response to alcohol	1
cellular response to ketone	1
cellular response to monoamine stimulus	1
response to catecholamine	1
cellular response to oxygen-containing compound	1
ribonucleoside triphosphate phosphatase activity	1
signaling receptor binding	1
signaling adaptor activity	1
enzyme binding	1
intracellular anatomical structure	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
extrinsic component of cytoplasmic side of plasma membrane	1
plasma membrane protein complex	1
GTPase complex	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

270 interactions, top by confidence:

A	B	Type	Score
GNG2	GNB1	psi-mi:“MI:0914”(association)	0.940
GNB1	GNG2	psi-mi:“MI:0407”(direct interaction)	0.940
GNB1	GNG2	psi-mi:“MI:0915”(physical association)	0.940
GNB1	GNAI1	psi-mi:“MI:0915”(physical association)	0.810
GNGT1	GNB1	psi-mi:“MI:0914”(association)	0.770
GNGT1	Ntsr1	psi-mi:“MI:0914”(association)	0.750
GNB1	GNG5	psi-mi:“MI:0915”(physical association)	0.740
GNG5	GNB1	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
HTT	GNB1	psi-mi:“MI:0915”(physical association)	0.670
GNG7	GNB1	psi-mi:“MI:0914”(association)	0.640
GNG10	GNB1	psi-mi:“MI:0914”(association)	0.640
GNG12	GNB1	psi-mi:“MI:0914”(association)	0.640
GNG3	GNB1	psi-mi:“MI:0914”(association)	0.640

BioGRID (504): GNB1 (Affinity Capture-MS), GNB1 (Affinity Capture-MS), GNB1 (Affinity Capture-MS), GNB1 (Affinity Capture-MS), GNB1 (Phenotypic Enhancement), GNB1 (Phenotypic Enhancement), COX4I1 (Co-fractionation), GNA11 (Co-fractionation), GNAQ (Co-fractionation), GNB1 (Affinity Capture-MS), GNB2L1 (Affinity Capture-Western), FYN (Affinity Capture-Western), PTK2 (Affinity Capture-Western), GNB1 (Proximity Label-MS), GNB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A223GEB2, A1L271, G4MQX3, O14435, O14775, O24456, O35353, O45040, P11017, P16520, P17343, P23232, P26308, P29387, P29829, P36408, P52287, P54311, P54313, P62871, P62872, P62873, P62874, P62879, P62880, P62881, P62882, P79147, P79959, P93339, P93397, P93398, P93563, Q08706, Q20636, Q39336, Q39836, Q40507, Q5GIS3, Q5R5W8

Diamond homologs: A0A223GEB2, A1CJY4, A1D7I5, A1L271, A2QEV8, A4R3M4, A4RDD7, A6H603, A7THX0, A8ILK1, B0XYC8, B3MJV8, B4HWV6, B4Q9T6, B6QC56, B8AP31, B8M0Q1, E3LB80, G0SC29, O14435, O14775, O35353, O45040, P11017, P16520, P17343, P18851, P23232, P26308, P29387, P29829, P36408, P49177, P49178, P52287, P54311, P54313, P61480, P62871, P62872

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
GNB1	up-regulates	PIK3CA	binding
SMO	up-regulates	GNB1	binding
FZD3	up-regulates	GNB1	binding
GNB1	up-regulates	PLCB2	binding
GNB1	up-regulates	PLCG1
GNB1	up-regulates	PI3K	binding
GNB1	“form complex”	GNB/GNG	binding
GNB1	down-regulates	PLCB1	binding
GPER1	“up-regulates activity”	GNB1	binding
GNB1	“up-regulates activity”	GNG2	binding
GNG2	“up-regulates activity”	GNB1	binding
GNB1	“up-regulates activity”	SRC
GPSM3	“down-regulates quantity by destabilization”	GNB1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 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
ADP signalling through P2Y purinoceptor 12	16	81.1×	3e-26
Prostacyclin signalling through prostacyclin receptor	13	79.7×	1e-21
G beta:gamma signalling through BTK	12	77.7×	1e-19
G beta:gamma signalling through PLC beta	12	69.9×	5e-19
G beta:gamma signalling through CDC42	12	69.9×	5e-19
Presynaptic function of Kainate receptors	12	66.6×	1e-18
Adrenaline,noradrenaline inhibits insulin secretion	15	60.3×	3e-22
G-protein activation	12	58.3×	7e-18

GO biological processes:

GO term	Partners	Fold	FDR
endocytosis	8	6.2×	1e-02
G protein-coupled receptor signaling pathway	19	5.6×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	18
Uncertain significance	116
Likely benign	162
Benign	22

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1194565	NM_002074.5(GNB1):c.347G>T (p.Gly116Val)	Pathogenic
1315576	NM_002074.5(GNB1):c.268-1G>T	Pathogenic
1315577	NM_002074.5(GNB1):c.272_275del (p.His91fs)	Pathogenic
1315578	NM_002074.5(GNB1):c.915_916del (p.Gly306fs)	Pathogenic
1315579	NM_002074.5(GNB1):c.917-1G>T	Pathogenic
1315581	NM_002074.5(GNB1):c.341G>A (p.Cys114Tyr)	Pathogenic
1315582	NM_002074.5(GNB1):c.230G>T (p.Gly77Val)	Pathogenic
1321652	NM_002074.5(GNB1):c.163C>G (p.Leu55Val)	Pathogenic
1433729	NM_002074.5(GNB1):c.55C>T (p.Arg19Ter)	Pathogenic
1699320	NM_002074.5(GNB1):c.228T>A (p.Asp76Glu)	Pathogenic
1700090	NM_002074.5(GNB1):c.229G>T (p.Gly77Cys)	Pathogenic
2089091	NM_002074.5(GNB1):c.631_632del (p.Trp211fs)	Pathogenic
224711	NM_002074.5(GNB1):c.227A>G (p.Asp76Gly)	Pathogenic
224715	NM_002074.5(GNB1):c.239T>A (p.Ile80Asn)	Pathogenic
224717	NM_002074.5(GNB1):c.301A>G (p.Met101Val)	Pathogenic
2576056	NM_002074.5(GNB1):c.267+1dup	Pathogenic
2703061	NM_002074.5(GNB1):c.916+1G>T	Pathogenic
2733819	NM_002074.5(GNB1):c.1009A>C (p.Lys337Gln)	Pathogenic
3281766	NM_002074.5(GNB1):c.188G>A (p.Trp63Ter)	Pathogenic
3775807	NM_002074.5(GNB1):c.229G>C (p.Gly77Arg)	Pathogenic
3854495	NM_002074.5(GNB1):c.458_459dup (p.Asp154fs)	Pathogenic
4720311	NM_002074.5(GNB1):c.753dup (p.Leu252fs)	Pathogenic
4733774	NM_002074.5(GNB1):c.891G>A (p.Trp297Ter)	Pathogenic
521025	NM_002074.5(GNB1):c.1011_1013del (p.Lys337_Ile338delinsAsn)	Pathogenic
521213	NM_002074.5(GNB1):c.353A>G (p.Asp118Gly)	Pathogenic
812755	NM_002074.5(GNB1):c.352G>T (p.Asp118Tyr)	Pathogenic
986264	NM_002074.5(GNB1):c.640C>T (p.Arg214Ter)	Pathogenic
995962	NM_002074.5(GNB1):c.287G>T (p.Arg96Leu)	Pathogenic
1048759	NM_002074.5(GNB1):c.496T>C (p.Cys166Arg)	Likely pathogenic
1200272	NM_002074.5(GNB1):c.917-2A>G	Likely pathogenic

SpliceAI

2887 predictions. Top by Δscore:

Variant	Effect	Δscore
1:1789048:CGTA:C	donor_loss	1.0000
1:1789049:GTACC:G	donor_loss	1.0000
1:1789050:TA:T	donor_loss	1.0000
1:1789051:A:AC	donor_gain	1.0000
1:1789051:ACCTG:A	donor_gain	1.0000
1:1789052:C:CC	donor_gain	1.0000
1:1789052:CCTG:C	donor_gain	1.0000
1:1789052:CCTGC:C	donor_gain	1.0000
1:1789055:G:A	donor_gain	1.0000
1:1789265:AAGAA:A	acceptor_gain	1.0000
1:1789266:AGAA:A	acceptor_gain	1.0000
1:1789267:GAA:G	acceptor_gain	1.0000
1:1789268:AA:A	acceptor_gain	1.0000
1:1789270:C:CC	acceptor_gain	1.0000
1:1790390:CTCA:C	donor_loss	1.0000
1:1790391:TCA:T	donor_loss	1.0000
1:1790392:CA:C	donor_loss	1.0000
1:1790393:A:AC	donor_gain	1.0000
1:1790393:AC:A	donor_loss	1.0000
1:1790394:C:CT	donor_gain	1.0000
1:1790394:CG:C	donor_gain	1.0000
1:1790394:CGCA:C	donor_gain	1.0000
1:1790394:CGCAA:C	donor_gain	1.0000
1:1790592:GGGCA:G	acceptor_gain	1.0000
1:1790595:CA:C	acceptor_gain	1.0000
1:1790595:CACTG:C	acceptor_loss	1.0000
1:1790597:C:CC	acceptor_gain	1.0000
1:1790597:CTG:C	acceptor_loss	1.0000
1:1790598:T:G	acceptor_loss	1.0000
1:1790603:C:CT	acceptor_gain	1.0000

AlphaMissense

2248 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:1787339:A:G	W339R	1.000
1:1787339:A:T	W339R	1.000
1:1787347:A:G	L336P	1.000
1:1787347:A:T	L336H	1.000
1:1787356:T:A	D333V	1.000
1:1787356:T:G	D333A	1.000
1:1787357:C:A	D333Y	1.000
1:1787357:C:G	D333H	1.000
1:1787358:C:A	W332C	1.000
1:1787358:C:G	W332C	1.000
1:1787359:C:A	W332L	1.000
1:1787359:C:G	W332S	1.000
1:1787360:A:G	W332R	1.000
1:1787360:A:T	W332R	1.000
1:1787362:G:A	S331F	1.000
1:1787362:G:T	S331Y	1.000
1:1787363:A:G	S331P	1.000
1:1787365:C:A	G330V	1.000
1:1787365:C:T	G330E	1.000
1:1787366:C:A	G330W	1.000
1:1787366:C:G	G330R	1.000
1:1787366:C:T	G330R	1.000
1:1787368:G:A	T329I	1.000
1:1787368:G:C	T329R	1.000
1:1787368:G:T	T329K	1.000
1:1787403:G:C	C317W	1.000
1:1787404:C:T	C317Y	1.000
1:1787406:G:C	S316R	1.000
1:1787406:G:T	S316R	1.000
1:1787407:C:A	S316I	1.000

dbSNP variants (sampled 300 via entrez): RS1000005292 (1:1811755 C>A), RS1000006407 (1:1823395 G>A), RS1000010731 (1:1881787 G>C), RS1000013294 (1:1833569 A>G), RS1000022324 (1:1868238 C>G,T), RS1000034471 (1:1862595 G>A,T), RS1000052204 (1:1857105 T>C), RS1000064792 (1:1827866 T>C), RS1000074597 (1:1828268 C>T), RS1000075421 (1:1887159 G>A,C), RS1000107677 (1:1863930 G>A), RS1000142481 (1:1839098 A>C,G), RS1000168834 (1:1794305 G>A), RS1000187595 (1:1800885 T>C), RS1000192650 (1:1828020 G>A)

Disease associations

OMIM: gene MIM:139380 | disease phenotypes: MIM:616973, MIM:614286

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal dominant 42	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
intellectual disability, autosomal dominant 42	Definitive	AD

Mondo (14): intellectual disability, autosomal dominant 42 (MONDO:0014855), acute lymphoblastic leukemia (MONDO:0004967), myelodysplastic syndrome (MONDO:0018881), intellectual disability (MONDO:0001071), strabismus (MONDO:0003432), dystonic disorder (MONDO:0003441), pathologic nystagmus (MONDO:0004843), hypothyroidism (MONDO:0005420), cerebral palsy (MONDO:0006497), cleft palate (MONDO:0016064), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258), microcephaly (MONDO:0001149), autosomal dominant non-syndromic intellectual disability (MONDO:0015802)

Orphanet (8): Global developmental delay-neuro-ophthalmological abnormalities-seizures-intellectual disability syndrome (Orphanet:488613), Acute lymphoblastic leukemia (Orphanet:513), Myelodysplastic syndrome (Orphanet:52688), Cleft palate (Orphanet:2014), Cerebral visual impairment (Orphanet:447788), Autosomal dominant non-syndromic intellectual disability (Orphanet:178469), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

90 total (30 of 90 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000011	Neurogenic bladder
HP:0000074	Ureteropelvic junction obstruction
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000322	Short philtrum
HP:0000358	Posteriorly rotated ears
HP:0000396	Overfolded helix
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000565	Esotropia
HP:0000577	Exotropia
HP:0000617	Abnormality of ocular smooth pursuit
HP:0000639	Nystagmus
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0000851	Congenital hypothyroidism
HP:0001181	Adducted thumb
HP:0001182	Tapered finger
HP:0001188	Hand clenching
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002783_250	Body mass index	6.000000e-07
GCST002783_429	Body mass index	8.000000e-07
GCST005951_34	Body mass index	3.000000e-08
GCST007094_106	Diastolic blood pressure	5.000000e-10
GCST007099_125	Systolic blood pressure	3.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D020821	Dystonic Disorders	C10.228.662.300
D007037	Hypothyroidism	C19.874.482
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
D013285	Strabismus	C10.292.562.887; C11.590.810

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3721304 (SINGLE PROTEIN), CHEMBL3883319 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,372 (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
CHEMBL87223	AMINOQUINURIDE	2	1,372

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

ChEMBL bioactivities

26 potent at pChembl≥5 of 46 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.00	IC50	100	nM	CHEMBL3728058
7.00	IC50	100	nM	CHEMBL487046
6.89	IC50	130	nM	CHEMBL1723511
6.70	IC50	200	nM	CHEMBL502775
6.70	IC50	200	nM	CHEMBL3733064
6.70	IC50	200	nM	CHEMBL3728757
6.70	IC50	200	nM	CHEMBL3732105
6.70	IC50	200	nM	CHEMBL4469620
6.70	IC50	200	nM	CHEMBL487046
6.60	IC50	250	nM	CHEMBL4443974
6.16	IC50	700	nM	CHEMBL3727794
6.16	IC50	700	nM	CHEMBL471004
5.70	IC50	2000	nM	CHEMBL203722
5.70	IC50	2000	nM	CHEMBL3728876
5.60	IC50	2500	nM	CHEMBL1208090
5.59	Kd	2553	nM	CHEMBL5653589
5.59	ED50	2553	nM	CHEMBL5653589
5.52	IC50	3000	nM	CHEMBL487046
5.30	IC50	5000	nM	CHEMBL3728247
5.30	IC50	5000	nM	AMINOQUINURIDE
5.30	IC50	5000	nM	CHEMBL1178292
5.22	IC50	6000	nM	CHEMBL1208442
5.10	IC50	8000	nM	CHEMBL487046
5.00	IC50	1e+04	nM	CHEMBL471225

PubChem BioAssay actives

7 with measured affinity, of 9 total; 7 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
8-(3,4,5-trihydroxy-6-oxoxanthen-9-yl)naphthalene-1-carboxylic acid	1559772: Inhibition of G-protein beta1gamma2 (unknown origin) by flow cytometry	ic50	0.1300	uM
2-(3,4,5-trihydroxy-6-oxoxanthen-9-yl)cyclohexane-1-carboxylic acid	1559772: Inhibition of G-protein beta1gamma2 (unknown origin) by flow cytometry	ic50	0.2000	uM
3’,4’,5’,6’-tetrahydroxyspiro[2-benzofuran-3,9’-xanthene]-1-one	1559772: Inhibition of G-protein beta1gamma2 (unknown origin) by flow cytometry	ic50	0.2000	uM
7,8,9,10,11,11-hexachloro-4-(3,4,5-trihydroxy-6-oxoxanthen-9-yl)tricyclo[4.4.1.01,6]undec-8-ene-3-carboxylic acid	1559772: Inhibition of G-protein beta1gamma2 (unknown origin) by flow cytometry	ic50	0.2500	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148443: Binding affinity to human GNB1 incubated for 45 mins by Kinobead based pull down assay	kd	2.5531	uM
7-amino-1,2,3,10-tetramethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-one	1559772: Inhibition of G-protein beta1gamma2 (unknown origin) by flow cytometry	ic50	5.0000	uM
1,3-bis(4-amino-2-methylquinolin-6-yl)urea	1559772: Inhibition of G-protein beta1gamma2 (unknown origin) by flow cytometry	ic50	5.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression, increases methylation, affects expression	3
bisphenol A	decreases expression, increases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Hydrogen Peroxide	affects cotreatment, increases expression, decreases expression	2
Nickel	increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Theophylline	affects cotreatment, increases expression, decreases expression	2
Valproic Acid	decreases expression, increases methylation	2
FR900359	increases phosphorylation	1
beauvericin	affects cotreatment, increases expression	1
2,4,6-tribromophenol	increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
pirinixic acid	affects binding, decreases expression, increases activity	1
decabromobiphenyl ether	increases expression	1
kojic acid	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
chloropicrin	decreases expression	1
enniatins	affects cotreatment, 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
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
5-amino-2-methylsulfanyl-4-(3-(2-morpholin-4-ylacetylamino)phenyl)thieno(2,3-d)pyrimidine-6-carboxylic acid tert-butylamide	affects binding	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651485	Binding	Binding affinity to human GNB1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

9 cell lines: 5 cancer cell line, 4 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B1DL	Abcam HCT 116 GNB1 KO	Cancer cell line	Male
CVCL_B1T1	Abcam HeLa GNB1 KO	Cancer cell line	Female
CVCL_C1MF	ALL-VG TKI-resistant	Cancer cell line	Male
CVCL_D7QQ	Ubigene A-549 GNB1 KO	Cancer cell line	Male
CVCL_E0DW	Ubigene HeLa GNB1 KO	Cancer cell line	Female
CVCL_E7SV	GNB1 FiPS1-Ep6F-1	Induced pluripotent stem cell	Male
CVCL_E7SW	GNB1 FiPS2-Ep6F-6	Induced pluripotent stem cell	Male
CVCL_E7SX	GNB1 FiPS3-Ep6F-2	Induced pluripotent stem cell	Female
CVCL_E7SY	GNB1 FiPS4-Ep6F-12	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00114348	PHASE4	COMPLETED	ALL-REZ BFM 2002: Multi-Center Study for Children With Relapsed Acute Lymphoblastic Leukemia
NCT00192673	PHASE4	UNKNOWN	Poly(Ethylene Glycol)(PEG)-Asparaginase During Two Treatment Courses
NCT00222612	PHASE4	UNKNOWN	Medical Research Council (MRC) Working Party on Leukaemia in Children UK National Acute Lymphoblastic Leukaemia (ALL) Trial: UKALL 2003
NCT00411541	PHASE4	COMPLETED	Pulses of Vincristine and Dexamethasone in BFM Protocols for Children With Acute Lymphoblastic Leukemia
NCT00494897	PHASE4	COMPLETED	PETHEMA LAL-RI/96: Treatment for Patients With Standard Risk Acute Lymphoblastic Leukemia
NCT00526175	PHASE4	COMPLETED	LAL-BR/2001: Study Treatment to Low Risk ALL
NCT00526305	PHASE4	COMPLETED	LAL-Ph-2000: Treatment of Acute Lymphoblastic Leukemia Chromosome Philadelphia Positive
NCT00526409	PHASE4	COMPLETED	LAL-AR-N-2005:Study Treatment for Children High Risk Acute Lymphoblastic Leukemia
NCT00576472	PHASE4	COMPLETED	Learning Impairments Among Survivors of Childhood Cancer
NCT00797810	PHASE4	UNKNOWN	Intensification Therapy of Mature B-ALL, Burkitt and Burkitt Like and Other High Grade Non-Hodgkin’s Lymphoma in Adults
NCT00846703	PHASE4	UNKNOWN	The GD-2008 ALL Protocol for Childhood Acute Lymphoblastic Leukemia
NCT00853008	PHASE4	COMPLETED	Treatment of High Risk Adult Acute Lymphoblastic Leukemia
NCT01358201	PHASE4	UNKNOWN	PETHEMA LAL-07FRAIL: All Treatment In Fragile Patients Ph’ Negative Over 55 Years
NCT01358253	PHASE4	COMPLETED	Rituximab Plus Chemotherapy for CD20+ Adult Acute Lymphoblastic Leukemia
NCT01366898	PHASE4	UNKNOWN	Protocol For the Treatment Acute Lymphoblastic Leukemia With Ph ‘Negative in Elderly Patients (> 55 Years)
NCT01735955	PHASE4	COMPLETED	Study to Allow Access to Nilotinib for Patients Who Are on Nilotinib Treatment in a Novartis-sponsored Study
NCT01873807	PHASE4	UNKNOWN	HD-Idarubicin/Etoposide Intensified Conditioning Regimen Allo-HSCT for Adult ALL
NCT01906671	PHASE4	UNKNOWN	Study on Two Different Formulations of 6-mercaptopurine. Tablet Versus Oral Liquid
NCT02447718	PHASE4	COMPLETED	Vaccinating Children After Chemotherapy
NCT02670564	PHASE4	UNKNOWN	ALL SCTped FORUM - Pharmacogenomic Study (add-on Study)
NCT02894645	PHASE4	UNKNOWN	Malaysia-Singapore Acute Lymphoblastic Leukemia 2010 Study
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT02953730	PHASE4	COMPLETED	The Study on the Pharmacokinetics of PEG-rhG-CSF in Children and Adolescents
NCT03677596	PHASE4	COMPLETED	A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients
NCT03920813	PHASE4	UNKNOWN	Determinants of Mercaptopurine Toxicity in Paediatric Acute Lymphoblastic Leukemia Maintenance Therapy
NCT05133310	PHASE4	UNKNOWN	Effect of Simvastatin on Sepsis and Febrile Neutropenia in Patients With Acute Lymphoblastic Leukemia
NCT05687032	PHASE4	COMPLETED	A Study of Inotuzumab Ozogamicin in Chinese Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
NCT06289673	PHASE4	RECRUITING	Identification of Necessary Information for Treatment Induction in Newly Diagnosed Acute Lymphoblastic Leukemia/Lymphoma
NCT06918054	PHASE4	RECRUITING	Hepatoprotective for Children and Adolescent With Acute Lymphoblastic Leukemia
NCT06918080	PHASE4	ACTIVE_NOT_RECRUITING	Hepatoprotective Measures for Children at High Risk of NAFLD
NCT07016165	PHASE4	RECRUITING	Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT07320534	PHASE4	NOT_YET_RECRUITING	Levofloxacin Prophylaxis to Prevent First Febrile Neutropenia in Pediatric ALL During Induction Phase
NCT00075725	PHASE3	COMPLETED	Dexamethasone Compared With Prednisone During Induction Therapy and Methotrexate With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia
NCT00103285	PHASE3	COMPLETED	Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
NCT00131027	PHASE3	UNKNOWN	High-Dose Methotrexate (MTX) for Adult Acute Lymphoblastic Leukemia (ALL)
NCT00137111	PHASE3	COMPLETED	Therapy for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
NCT00152139	PHASE3	COMPLETED	Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00165087	PHASE3	TERMINATED	Treatment of Childhood Acute Lymphoblastic Leukemia
NCT00165178	PHASE3	COMPLETED	Treatment of Acute Lymphoblastic Leukemia in Children
NCT00187005	PHASE3	TERMINATED	Total Therapy Study XIV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia