GNAO1

Summary

GNAO1 (G protein subunit alpha o1, HGNC:4389) is a protein-coding gene on chromosome 16q13, encoding Guanine nucleotide-binding protein G(o) subunit alpha (P09471). Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.

The protein encoded by this gene represents the alpha subunit of the Go heterotrimeric G-protein signal-transducing complex. Defects in this gene are a cause of early-onset epileptic encephalopathy. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2775 — RefSeq curated summary.

At a glance

• Gene–disease (curated): movement disorder (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 14
• Clinical variants (ClinVar): 588 total — 50 pathogenic, 41 likely-pathogenic
• Phenotypes (HPO): 81
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_020988

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4389
Approved symbol	GNAO1
Name	G protein subunit alpha o1
Location	16q13
Locus type	gene with protein product
Status	Approved
Aliases	G-ALPHA-o
Ensembl gene	ENSG00000087258
Ensembl biotype	protein_coding
OMIM	139311
Entrez	2775

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 11 protein_coding, 7 retained_intron, 6 protein_coding_CDS_not_defined, 5 nonsense_mediated_decay

ENST00000262493, ENST00000262494, ENST00000562316, ENST00000563440, ENST00000563661, ENST00000564727, ENST00000564798, ENST00000565363, ENST00000568375, ENST00000569295, ENST00000570235, ENST00000638185, ENST00000638210, ENST00000638705, ENST00000638836, ENST00000639055, ENST00000639251, ENST00000639268, ENST00000639341, ENST00000639770, ENST00000639787, ENST00000639966, ENST00000640390, ENST00000640469, ENST00000640560, ENST00000640893, ENST00000675160, ENST00000714052, ENST00000873096

RefSeq mRNA: 2 — MANE Select: NM_020988 NM_020988, NM_138736

CCDS: CCDS10756, CCDS10757

Canonical transcript exons

ENST00000262493 — 9 exons

Exon	Start	End
ENSE00000852753	56336731	56336860
ENSE00001204552	56328631	56328791
ENSE00001322402	56354866	56355081
ENSE00001664398	56351384	56351537
ENSE00002608417	56191489	56192353
ENSE00003570668	56275931	56276072
ENSE00003789471	56334729	56334857
ENSE00004022637	56192574	56192616
ENSE00004022640	56356103	56357444

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 99.32.

FANTOM5 (CAGE): breadth broad, TPM avg 27.3688 / max 1047.8138, expressed in 604 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154189	11.5079	387
154185	6.6017	490
154188	1.7592	237
154186	1.2420	266
154190	1.1009	147
154192	1.0101	133
154193	0.7938	115
154194	0.7697	123
154187	0.7651	231
154191	0.5734	118

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.32	gold quality
superficial temporal artery	UBERON:0001614	99.12	silver quality
entorhinal cortex	UBERON:0002728	98.76	gold quality
prefrontal cortex	UBERON:0000451	98.74	gold quality
superior frontal gyrus	UBERON:0002661	98.74	gold quality
right frontal lobe	UBERON:0002810	98.73	gold quality
putamen	UBERON:0001874	98.68	gold quality
postcentral gyrus	UBERON:0002581	98.61	gold quality
buccal mucosa cell	CL:0002336	98.60	gold quality
caudate nucleus	UBERON:0001873	98.59	gold quality
primary visual cortex	UBERON:0002436	98.58	gold quality
parietal lobe	UBERON:0001872	98.56	gold quality
nucleus accumbens	UBERON:0001882	98.53	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.53	gold quality
temporal lobe	UBERON:0001871	98.49	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.47	gold quality
frontal cortex	UBERON:0001870	98.45	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.43	silver quality
amygdala	UBERON:0001876	98.42	gold quality
neocortex	UBERON:0001950	98.38	gold quality
occipital lobe	UBERON:0002021	98.36	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.34	gold quality
telencephalon	UBERON:0001893	98.32	gold quality
cerebellar cortex	UBERON:0002129	98.31	gold quality
cerebellar hemisphere	UBERON:0002245	98.30	gold quality
cerebral cortex	UBERON:0000956	98.26	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.26	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.23	gold quality
cingulate cortex	UBERON:0003027	98.14	gold quality
Ammon’s horn	UBERON:0001954	98.10	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	41.77
E-GEOD-137537	yes	13.56
E-GEOD-83139	yes	10.63
E-MTAB-6678	yes	7.24
E-ANND-3	yes	5.18
E-HCAD-10	yes	4.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

102 targeting GNAO1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 38)

• a novel role in the signal transduction of thrombin receptors in HMECs (human microvascular endothelial cells) that regulates calcium signaling and cytoskeletal rearrangements (PMID:12039967)
• study suggests that one of the functions of Goalpha in the brain is to mediate extracellular signal-regulated kinase activation by G protein-coupled receptors (PMID:12911629)
• Activated Goalpha interacted directly with PLZF, and enhanced its function as a transcriptional and cell growth suppressor. (PMID:18262754)
• the successful purification of functionally intact Gbeta5-free recombinant RGS11 was reported that differentially interact with R7BP and Galpha(oa). (PMID:19497306)
• A switch in G-protein coupling, in which glutamate775lysine loses G(o) subunit coupling but retains coupling to G(i), may explain the highly specialized metabotropic glutamate receptor mGlu6 phenotype. (PMID:19666700)
• CKbeta8- and CKbeta8-1-induced activation of ERK1/2 is mediated by the G(i)/G(o) protein, PLC, and PKCdelta. (PMID:20097574)
• Data reveal a change in the repertoire of Galpha(i/o) subunits during T cell differentiation and suggest functional equivalence among Galpha(i/o) subunits irrespective of their relative abundance. (PMID:20829352)
• Data show that HEK293T cells transfected with estrogen receptor alpha (ERalpha)+/-Galpha(o) revealed that Galpha(o) stimulated phosphorylation of ERK MAP kinases ERK 1/2 and subsequently increased the phosphorylation of ERalpha on serine 118. (PMID:22562654)
• Down-regulation of GNAO1 increases cell proliferation, while suppressing the senescence of hepatocellular carcinoma cells. (PMID:23984917)
• These data suggest that aberrant Galphao signaling can cause multiple neurodevelopmental phenotypes, including epileptic encephalopathy and involuntary movements. (PMID:23993195)
• the present study is the first to demonstrate that GNAO1 is overexpressed in GC and that its overexpression correlates with poor prognosis, as it promotes gastric cancer cell viability. (PMID:24366063)
• Genetic variants of BCL2, GNAO1, and CHD2 are associated with non-obstructive azoospermia risk. (PMID:24549219)
• Galphao-R243H has a mild decrease in nucleotide affinity that causes rapid nucleotide turnover and subsequent hyperactivity in cancer (PMID:24982418)
• Phenotypic spectrum of novel GNAO1 variants in four unrelated female patients included epileptic encephalopathy and involuntary movements with severe developmental delay. (PMID:25966631)
• authors report 2 cases of brothers with a severe movement disorder and hypotonia without epilepsy who have been confirmed by whole exome sequencing to have a novel mutation in GNAO1 (PMID:26060304)
• Endothelial cells in capillary malformations are enriched for GNAQ mutations and are likely responsible for the pathophysiology underlying capillary malformation. (PMID:26368330)
• GNAO1 is a disease-causing gene for the autosomal dominant form of early infantile epileptic encephalopathy. The novel pathogenic variant identified in should contribute to our understanding of the expanding spectrum of infantile-onset epilepsy. (PMID:26485252)
• Taken together, the data presented here suggest that TLR2 activation in human mast cells promotes the release of inflammatory mediators via distinct signaling pathways that partially depend on the action of Go proteins. (PMID:27515449)
• The neurological phenotypes associated with GNAO1 mutations appear to lie on a spectrum, and it is possible that the c.607G>A (p.Gly203Arg) variant characterizes a phenotype with both severe epilepsy and chorea. (PMID:28202424)
• first report of siblings of opposite sex harboring the same GNAO1 mutation but showing differences in phenotype with pronounced dystonia in the boy and epilepsy in his sister. (PMID:28628939)
• Study identified distinct biochemical mechanisms of pathogenic human GNAO1 mutations that may improve the understanding of the heterogeneous clinical spectrum of GNAO1-associated epilepsy and movement disorders. Furthermore, these results also carry significant implications for personalized therapeutics in GNAO1 encephalopathies. (PMID:28747448)
• GNAO1 transcription was inhibited by promoter hypermethylation, contributing to its low expression. It was further revealed that the silencing effect was regulated by methyltransferase 1 (DNMT1), and was further enhanced by transforming growth factor beta (TGF-beta). (PMID:29709639)
• Pediatric ependymoma: GNAO1, ASAH1, IMMT and IPO7 protein expression and 5-year prognosis correlation. (PMID:31505435)
• Identification of functional cooperative mutations of GNAO1 in human acute lymphoblastic leukemia. (PMID:32898863)
• GNAO1 organizes the cytoskeletal remodeling and firing of developing neurons. (PMID:33107105)
• Structures of the glucocorticoid-bound adhesion receptor GPR97-Go complex. (PMID:33408414)
• Clinical and molecular characterizations of 11 new patients with type 1 Feingold syndrome: Proposal for selecting diagnostic criteria and further genetic testing in patients with severe phenotype. (PMID:33442900)
• GNAO1 as a Novel Predictive Biomarker for Late Relapse in Hepatocellular Carcinoma. (PMID:34900204)
• G0S2 regulates innate immunity in Kawasaki disease via lncRNA HSD11B1-AS1. (PMID:35292727)
• Highlighting the Dystonic Phenotype Related to GNAO1. (PMID:35722775)
• Visual Function in Children with GNAO1-Related Encephalopathy. (PMID:36980817)
• Dystonic Cerebral Palsy Phenotype Due to GNAO1 Variant Responsive to Levodopa. (PMID:37034444)
• Genotype-phenotype correlation and treatment effects in young patients with GNAO1-associated disorders. (PMID:37225406)
• Clinical Cases and the Molecular Profiling of a Novel Childhood Encephalopathy-Causing GNAO1 Mutation P170R. (PMID:37887313)
• AAV9-Mediated Intrastriatal Delivery of GNAO1 Reduces Hyperlocomotion in Gnao1 Heterozygous R209H Mutant Mice. (PMID:38866563)
• Neomorphic Galphao mutations gain interaction with Ric8 proteins in GNAO1 encephalopathies. (PMID:38874642)
• Clinical and Molecular Profiling in GNAO1 Permits Phenotype-Genotype Correlation. (PMID:38881224)
• CircGNAO1 suppresses hepatocellular carcinoma progression and metastasis via sponging miR-182-5p and regulating FOXO1 expression. (PMID:39098231)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gnao1a	ENSDARG00000016676
danio_rerio	gnao1b	ENSDARG00000036058
mus_musculus	Gnao1	ENSMUSG00000031748
drosophila_melanogaster	Galphao	FBGN0001122
caenorhabditis_elegans	goa-1	WBGENE00001648

Paralogs (15): GNA15 (ENSG00000060558), GNAI3 (ENSG00000065135), GNAS (ENSG00000087460), GNA11 (ENSG00000088256), GNAT1 (ENSG00000114349), GNAI2 (ENSG00000114353), GNA13 (ENSG00000120063), GNAI1 (ENSG00000127955), GNAZ (ENSG00000128266), GNAT2 (ENSG00000134183), GNAL (ENSG00000141404), GNA12 (ENSG00000146535), GNA14 (ENSG00000156049), GNAQ (ENSG00000156052), GNAT3 (ENSG00000214415)

Protein

Protein identifiers

Guanine nucleotide-binding protein G(o) subunit alpha — P09471 (reviewed: P09471)

All UniProt accessions (13): P09471, A0A087WTB6, A0A1W2PP38, A0A1W2PP87, A0A1W2PPG6, A0A1W2PQ24, A0A1W2PQK2, A0A1W2PRE1, A0A1W2PRJ7, A0A1W2PS82, A0A6Q8PGR1, H3BNR5, H3BTM2

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels.

Subunit / interactions. G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Forms a complex with GNB1 and GNG3. Interacts with RGS14. Interacts with RGS16. Interacts with RGS19. Interacts (when palmitoylated) with ADGRG3.

Subcellular location. Cell membrane. Membrane.

Post-translational modifications. Histaminylated at Gln-205 residues by TGM2. Palmitoylated at Cys-351, leading to binding to ADGRG3.

Disease relevance. Developmental and epileptic encephalopathy 17 (DEE17) [MIM:615473] A severe neurologic disorder characterized by onset of intractable seizures in the first weeks or months of life and usually associated with EEG abnormalities. Affected infants have very poor psychomotor development and may have brain abnormalities, such as cerebral atrophy or thin corpus callosum. Some patients may show involuntary movements. The disease is caused by variants affecting the gene represented in this entry. Neurodevelopmental disorder with involuntary movements (NEDIM) [MIM:617493] A neurodevelopmental disorder manifesting with a wide range of clinical symptoms. Clinical features range from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior and epileptic encephalopathy, to a milder phenotype featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia, and mild epilepsy. Hyperkinetic movements are often exacerbated by specific triggers, such as illness, emotion and high ambient temperature. Some patients have brain abnormalities, such as cerebral atrophy or thin corpus callosum. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The GTPase activity is promoted by GTPAse activators, such as RGS14, RGS16 and RGS19.

Similarity. Belongs to the G-alpha family. G(i/o/t/z) subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P09471-1	Alpha-1	yes
P09471-2	Alpha-2

RefSeq proteins (2): NP_066268, NP_620073 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001019	Gprotein_alpha_su	Family
IPR001408	Gprotein_alpha_I	Family
IPR011025	GproteinA_insert	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00503

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (82 total): sequence variant 17, helix 16, binding site 14, strand 11, region of interest 5, turn 5, modified residue 3, lipid moiety-binding region 3, sequence conflict 3, initiator methionine 1, chain 1, domain 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

86 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9BSB	ELECTRON MICROSCOPY	2.32
9VJE	ELECTRON MICROSCOPY	2.47
9K20	ELECTRON MICROSCOPY	2.65
9VJ5	ELECTRON MICROSCOPY	2.69
8E9X	ELECTRON MICROSCOPY	2.7
9PLO	ELECTRON MICROSCOPY	2.74
9VNF	ELECTRON MICROSCOPY	2.74
8YN7	ELECTRON MICROSCOPY	2.77
8YN8	ELECTRON MICROSCOPY	2.77
9KVP	ELECTRON MICROSCOPY	2.79
7W2Z	ELECTRON MICROSCOPY	2.8
8XXH	ELECTRON MICROSCOPY	2.8
8DZQ	ELECTRON MICROSCOPY	2.82
9VMY	ELECTRON MICROSCOPY	2.86
8FN1	ELECTRON MICROSCOPY	2.88
8I95	ELECTRON MICROSCOPY	2.88
9KV6	ELECTRON MICROSCOPY	2.88
6K41	ELECTRON MICROSCOPY	2.9
7D77	ELECTRON MICROSCOPY	2.9
9DYE	ELECTRON MICROSCOPY	2.9
9VAU	ELECTRON MICROSCOPY	2.95
9DYD	ELECTRON MICROSCOPY	2.96
8XX6	ELECTRON MICROSCOPY	2.99
9VAV	ELECTRON MICROSCOPY	2.99
7EJ8	ELECTRON MICROSCOPY	3
8XYK	ELECTRON MICROSCOPY	3.03
9F33	ELECTRON MICROSCOPY	3.05
8XWV	ELECTRON MICROSCOPY	3.07
8Y0N	ELECTRON MICROSCOPY	3.07
9KUG	ELECTRON MICROSCOPY	3.07

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09471-F1	94.67	0.88

Antibody-complex structures (SAbDab): 62 — 6K41, 6OIK, 6WWZ, 7D77, 7EJ0, 7EJ8, 7EJA, 7EJK, 7QVM, 7T8X, 7T90, 7T94, 7T96, 7W2Z, 7W6P, 7W7E, 7XJJ, 7Y24, 8DZQ, 8E9X, 8FN1, 8HPT, 8HQC, 8I95, 8I97 (+37 more)

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): 47; 47; 48; 152; 176; 177; 178; 179; 182; 270; 273; 325 …

Post-translational modifications (6): 179, 205, 351, 2, 3, 351

Mutagenesis-validated functional residues (1):

Position	Phenotype
351	strong loss of binding to adgrg3.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-4086398	Ca2+ pathway

MSigDB gene sets: 505 (showing top): AHRARNT_01, GNF2_RTN1, CREL_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, PID_S1P_S1P1_PATHWAY, BENPORATH_ES_WITH_H3K27ME3, HNF3ALPHA_Q6, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, LFA1_Q6, TTTGTAG_MIR520D, GOBP_INSULIN_SECRETION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_HORMONE_LEVELS

GO Biological Process (12): obsolete vesicle docking involved in exocytosis (GO:0006904), muscle contraction (GO:0006936), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), adenylate cyclase-inhibiting serotonin receptor signaling pathway (GO:0007198), G protein-coupled dopamine receptor signaling pathway (GO:0007212), locomotory behavior (GO:0007626), regulation of heart contraction (GO:0008016), negative regulation of insulin secretion (GO:0046676), postsynaptic modulation of chemical synaptic transmission (GO:0099170), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (13): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), G-protein beta/gamma-subunit complex binding (GO:0031683), G protein-coupled serotonin receptor binding (GO:0031821), mu-type opioid receptor binding (GO:0031852), metal ion binding (GO:0046872), corticotropin-releasing hormone receptor 1 binding (GO:0051430), nucleotide binding (GO:0000166), protein binding (GO:0005515), adenylate cyclase regulator activity (GO:0010854), hydrolase activity (GO:0016787), guanyl nucleotide binding (GO:0019001)

GO Cellular Component (11): cytoplasm (GO:0005737), heterotrimeric G-protein complex (GO:0005834), plasma membrane (GO:0005886), dendrite (GO:0030425), presynaptic membrane (GO:0042734), cell body (GO:0044297), postsynaptic membrane (GO:0045211), parallel fiber to Purkinje cell synapse (GO:0098688), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Beta-catenin independent WNT signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
adenylate cyclase activity	2
G protein-coupled receptor signaling pathway	2
postsynapse	2
synaptic membrane	2
synapse	2
muscle system process	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
Gi/o-coupled serotonin receptor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
G protein-coupled serotonin receptor signaling pathway	1
synaptic transmission, dopaminergic	1
cellular response to dopamine	1
behavior	1
heart contraction	1
regulation of blood circulation	1
insulin secretion	1
negative regulation of protein secretion	1
regulation of insulin secretion	1
negative regulation of peptide hormone secretion	1
modulation of chemical synaptic transmission	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein-containing complex binding	1
G protein-coupled receptor binding	1
opioid receptor binding	1
cation binding	1
corticotropin-releasing hormone receptor binding	1
nucleoside phosphate binding	1

Protein interactions and networks

STRING

3224 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNAO1	RGS4	P49798	971
GNAO1	RGS7	P49802	970
GNAO1	RGS16	O15492	952
GNAO1	DRD2	P14416	911
GNAO1	RGS8	P57771	854
GNAO1	AVPR2	P30518	838
GNAO1	RIC8A	Q9NPQ8	786
GNAO1	GNB5	O14775	768
GNAO1	GNB4	Q9HAV0	762
GNAO1	RGS10	O43665	736
GNAO1	RGS14	O43566	734
GNAO1	RGS6	P49758	733
GNAO1	GNB1	P04697	731
GNAO1	SUCLG1	P53597	731
GNAO1	PLCB2	Q00722	715

IntAct

93 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
GNAO1	VCP	psi-mi:“MI:0915”(physical association)	0.670
GNAO1	HTT	psi-mi:“MI:0915”(physical association)	0.670
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
GNG8	GNB5	psi-mi:“MI:0914”(association)	0.640
Haus4	HAUS5	psi-mi:“MI:0915”(physical association)	0.560
CALR	GNAO1	psi-mi:“MI:0915”(physical association)	0.560
GNAO1	DLST	psi-mi:“MI:0915”(physical association)	0.560
ABCD3	GNAO1	psi-mi:“MI:0915”(physical association)	0.560
	GNAO1	psi-mi:“MI:0915”(physical association)	0.560
GNAO1	RPS6KA3	psi-mi:“MI:0915”(physical association)	0.560
GNAO1	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
GNAO1	CBX5	psi-mi:“MI:0915”(physical association)	0.560
GNAO1	NEK7	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (120): GNAO1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), GNAO1 (Co-fractionation), GNAO1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS)

ESM2 similar proteins: B0XRA0, B2RSH2, O13055, O13315, O42784, O74227, O74259, P04695, P04897, P04899, P08239, P08752, P08753, P08754, P09471, P10825, P11488, P16378, P18872, P20353, P20612, P27044, P27045, P30676, P30682, P30683, P38400, P38401, P38402, P38403, P38404, P38407, P50146, P50147, P51875, P51876, P51877, P59215, P59216, P63096

Diamond homologs: A2Y3B5, A8MTJ3, B0XRA0, B2RSH2, O04278, O04279, O13055, O13315, O14438, O15976, O42784, O74227, O74259, O95837, P04695, P04696, P04897, P04899, P08239, P08752, P08753, P08754, P09471, P0C7Q4, P0CN96, P0CN97, P10824, P10825, P11488, P16378, P16894, P18064, P18872, P19087, P20353, P20612, P26981, P27044, P27045, P28051

SIGNOR signaling

103 interactions.

A	Effect	B	Mechanism
CHRM2	up-regulates	GNAO1
GNAO1	up-regulates	TAOK1
GNAO1	up-regulates	TAOK2
GNAO1	“up-regulates activity”	NDN
CNR1	“up-regulates activity”	GNAO1
P2RY13	“up-regulates activity”	GNAO1	binding
CHRM2	“up-regulates activity”	GNAO1	binding
CHRM4	“up-regulates activity”	GNAO1	binding
GALR1	“up-regulates activity”	GNAO1	binding
GPR34	“up-regulates activity”	GNAO1	binding
HRH3	“up-regulates activity”	GNAO1	binding
SSTR5	“up-regulates activity”	GNAO1	binding
LTB4R	“up-regulates activity”	GNAO1	binding
GPR17	“up-regulates activity”	GNAO1	binding
HTR1A	“up-regulates activity”	GNAO1	binding
PRLHR	“up-regulates activity”	GNAO1	binding
BDKRB2	“up-regulates activity”	GNAO1	binding
LPAR1	“up-regulates activity”	GNAO1	binding
ADORA1	“up-regulates activity”	GNAO1	binding
ADRA2A	“up-regulates activity”	GNAO1	binding
ADRA2C	“up-regulates activity”	GNAO1	binding
CNR2	“up-regulates activity”	GNAO1	binding
DRD2	“up-regulates activity”	GNAO1	binding
DRD3	“up-regulates activity”	GNAO1	binding
DRD4	“up-regulates activity”	GNAO1	binding
GPR84	“up-regulates activity”	GNAO1	binding
HTR1E	“up-regulates activity”	GNAO1	binding
MTNR1A	“up-regulates activity”	GNAO1	binding
MTNR1B	“up-regulates activity”	GNAO1	binding
NPFFR1	“up-regulates activity”	GNAO1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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
Prostacyclin signalling through prostacyclin receptor	7	65.7×	4e-10
ADP signalling through P2Y purinoceptor 12	8	62.1×	1e-10
G beta:gamma signalling through BTK	6	59.5×	2e-08
G beta:gamma signalling through PLC beta	6	53.5×	3e-08
G beta:gamma signalling through CDC42	6	53.5×	3e-08
Presynaptic function of Kainate receptors	6	51.0×	4e-08
Adrenaline,noradrenaline inhibits insulin secretion	8	49.2×	3e-10
G-protein activation	6	44.6×	8e-08

GO biological processes:

GO term	Partners	Fold	FDR
G protein-coupled receptor signaling pathway	13	6.0×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	50
Likely pathogenic	41
Uncertain significance	171
Likely benign	219
Benign	44

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012170	NM_020988.3(GNAO1):c.136A>G (p.Lys46Glu)	Pathogenic
1012172	NM_020988.3(GNAO1):c.470T>C (p.Leu157Pro)	Pathogenic
1012173	NM_020988.3(GNAO1):c.810C>A (p.Asn270Lys)	Pathogenic
1016767	NM_020988.3(GNAO1):c.759dup (p.Ile254fs)	Pathogenic
1064445	NM_020988.3(GNAO1):c.723+2T>A	Pathogenic
1319183	NM_020988.3(GNAO1):c.608G>A (p.Gly203Glu)	Pathogenic
1374497	NM_020988.3(GNAO1):c.124G>A (p.Gly42Arg)	Pathogenic
1389555	NM_020988.3(GNAO1):c.155A>G (p.Gln52Arg)	Pathogenic
1432250	NM_020988.3(GNAO1):c.813G>T (p.Lys271Asn)	Pathogenic
1446069	NC_000016.9:g.(?56226148)(56226548_?)del	Pathogenic
1453190	NM_020988.3(GNAO1):c.602A>T (p.Asp201Val)	Pathogenic
1453470	NM_020988.3(GNAO1):c.617G>T (p.Arg206Leu)	Pathogenic
1459091	NM_020988.3(GNAO1):c.596T>C (p.Leu199Pro)	Pathogenic
1469197	NM_020988.3(GNAO1):c.1023CAT[2] (p.Ile344del)	Pathogenic
1685853	NM_020988.3(GNAO1):c.610G>C (p.Gly204Arg)	Pathogenic
1701291	NM_020988.3(GNAO1):c.736_738delinsAAA (p.Glu246Lys)	Pathogenic
1802165	NM_020988.3(GNAO1):c.17G>T (p.Ser6Ile)	Pathogenic
1802972	NM_020988.3(GNAO1):c.119G>C (p.Gly40Ala)	Pathogenic
208677	NM_020988.3(GNAO1):c.626G>A (p.Arg209His)	Pathogenic
208777	NM_020988.3(GNAO1):c.736G>A (p.Glu246Lys)	Pathogenic
2152262	NM_020988.3(GNAO1):c.155A>C (p.Gln52Pro)	Pathogenic
2499605	NM_020988.3(GNAO1):c.124G>C (p.Gly42Arg)	Pathogenic
2578317	NM_020988.3(GNAO1):c.723+1G>T	Pathogenic
265350	NM_020988.3(GNAO1):c.625C>T (p.Arg209Cys)	Pathogenic
2705877	NM_020988.3(GNAO1):c.398_402dup (p.Ser135fs)	Pathogenic
2759489	NM_020988.3(GNAO1):c.631A>C (p.Lys211Gln)	Pathogenic
280526	NM_020988.3(GNAO1):c.118G>T (p.Gly40Trp)	Pathogenic
2824114	NM_020988.3(GNAO1):c.133G>T (p.Gly45Ter)	Pathogenic
2825827	NM_020988.3(GNAO1):c.807_808delinsAC (p.Asn270His)	Pathogenic
3243367	NC_000016.9:g.(?56385276)(56388965_?)del	Pathogenic

SpliceAI

2381 predictions. Top by Δscore:

Variant	Effect	Δscore
16:56192349:GCTCG:G	donor_gain	1.0000
16:56192354:G:GG	donor_gain	1.0000
16:56192617:G:GG	donor_gain	1.0000
16:56275929:A:AG	acceptor_gain	1.0000
16:56275930:G:GG	acceptor_gain	1.0000
16:56275930:GGATC:G	acceptor_gain	1.0000
16:56276056:GTGA:G	donor_gain	1.0000
16:56276057:TGAT:T	donor_gain	1.0000
16:56276059:A:AG	donor_gain	1.0000
16:56276068:GAAAG:G	donor_gain	1.0000
16:56276069:AAAGG:A	donor_loss	1.0000
16:56276070:AAGGT:A	donor_loss	1.0000
16:56276071:AGG:A	donor_loss	1.0000
16:56276072:GGTAG:G	donor_loss	1.0000
16:56276074:T:A	donor_loss	1.0000
16:56328625:TCACA:T	acceptor_loss	1.0000
16:56328626:CACAG:C	acceptor_loss	1.0000
16:56328627:ACAGG:A	acceptor_loss	1.0000
16:56328628:CAGGC:C	acceptor_loss	1.0000
16:56328629:A:AG	acceptor_gain	1.0000
16:56328630:G:GA	acceptor_loss	1.0000
16:56328630:G:GG	acceptor_gain	1.0000
16:56328630:GGCT:G	acceptor_gain	1.0000
16:56328762:G:GT	donor_gain	1.0000
16:56328788:AATA:A	donor_gain	1.0000
16:56328789:ATA:A	donor_gain	1.0000
16:56328790:TA:T	donor_gain	1.0000
16:56328792:G:GG	donor_gain	1.0000
16:56334857:GGTG:G	donor_loss	1.0000
16:56334858:G:C	donor_loss	1.0000

AlphaMissense

2367 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:56192345:T:A	L37H	1.000
16:56192345:T:C	L37P	1.000
16:56192351:T:A	L39H	1.000
16:56192353:G:A	G40R	1.000
16:56192353:G:C	G40R	1.000
16:56192353:G:T	G40W	1.000
16:56192574:G:A	G40E	1.000
16:56192574:G:T	G40V	1.000
16:56192585:T:C	S44P	1.000
16:56192588:G:A	G45R	1.000
16:56192588:G:C	G45R	1.000
16:56192589:G:A	G45E	1.000
16:56192589:G:C	G45A	1.000
16:56192589:G:T	G45V	1.000
16:56192591:A:C	K46Q	1.000
16:56192592:A:T	K46I	1.000
16:56192593:A:C	K46N	1.000
16:56192593:A:T	K46N	1.000
16:56192594:A:C	S47R	1.000
16:56192594:A:T	S47C	1.000
16:56192595:G:T	S47I	1.000
16:56192596:C:A	S47R	1.000
16:56192596:C:G	S47R	1.000
16:56192598:C:T	T48I	1.000
16:56192611:G:C	Q52H	1.000
16:56192611:G:T	Q52H	1.000
16:56334785:A:T	D174V	1.000
16:56334791:T:A	L176H	1.000
16:56334791:T:C	L176P	1.000
16:56334794:G:C	R177P	1.000

dbSNP variants (sampled 300 via entrez): RS1000037397 (16:56326565 G>A), RS1000068281 (16:56209280 A>G), RS1000069078 (16:56312808 A>C,G), RS1000093696 (16:56344479 C>T), RS1000113975 (16:56271052 A>G), RS1000153111 (16:56350055 G>A), RS1000156689 (16:56257147 G>A), RS1000162231 (16:56240463 T>G), RS1000179290 (16:56195020 T>C,G), RS1000207238 (16:56198711 A>G), RS1000297074 (16:56247068 A>G), RS1000365647 (16:56294361 A>G), RS1000385036 (16:56205856 G>A), RS1000425910 (16:56300451 C>G,T), RS1000441413 (16:56349833 T>C,G)

Disease associations

OMIM: gene MIM:139311 | disease phenotypes: MIM:615473, MIM:617493, MIM:308350

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 17	Definitive	Autosomal dominant
movement disorder	Definitive	Autosomal dominant
genetic developmental and epileptic encephalopathy	Definitive	Autosomal dominant
neurodevelopmental disorder with involuntary movements	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
movement disorder	Definitive	AD
genetic developmental and epileptic encephalopathy	Definitive	AD

Mondo (11): early-infantile DEE (MONDO:0800491), developmental and epileptic encephalopathy, 17 (MONDO:0014199), neurodevelopmental disorder with involuntary movements (MONDO:0060491), developmental and epileptic encephalopathy (MONDO:0100620), congenital nervous system disorder (MONDO:0002320), genetic developmental and epileptic encephalopathy (MONDO:0100062), movement disorder (MONDO:0005395), choreatic disease (MONDO:0001595), intellectual disability (MONDO:0001071), developmental and epileptic encephalopathy, 1 (MONDO:0010632), microcephaly (MONDO:0001149)

Orphanet (6): Early infantile developmental and epileptic encephalopathy (Orphanet:1934), GNAO1-related developmental delay-seizures-movement disorder spectrum (Orphanet:592564), Benign hereditary chorea (Orphanet:1429), Rare genetic intellectual disability (Orphanet:183757), Early myoclonic encephalopathy (Orphanet:1935), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

81 total (30 of 81 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000054	Micropenis
HP:0000070	Ureterocele
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000340	Sloping forehead
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000729	Autistic behavior
HP:0000752	Hyperactivity
HP:0000826	Precocious puberty
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001254	Lethargy
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001272	Cerebellar atrophy
HP:0001290	Generalized hypotonia
HP:0001302	Pachygyria
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001500	Broad finger
HP:0001508	Failure to thrive
HP:0001537	Umbilical hernia
HP:0001629	Ventricular septal defect

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST005757_3	Dimensional psychopathology (Positive)	4.000000e-07
GCST007096_223	Pulse pressure	2.000000e-09
GCST007268_53	Diastolic blood pressure	2.000000e-08
GCST007393_8	Mitochondrial DNA copy number	8.000000e-07
GCST007559_23	Sleep duration (short sleep)	2.000000e-08
GCST007565_133	Morning person	6.000000e-26
GCST007576_22	Chronotype	6.000000e-26
GCST007576_403	Chronotype	2.000000e-10
GCST009391_1808	Metabolite levels	9.000000e-06
GCST010166_2	Cardioembolic stroke (CCSp classification)	5.000000e-08
GCST010241_307	Apolipoprotein A1 levels	2.000000e-08
GCST010241_332	Apolipoprotein A1 levels	3.000000e-08
GCST010242_152	HDL cholesterol levels	5.000000e-12
GCST011494_71	Daytime nap	6.000000e-17

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0009097	positive domain measurement
EFO:0005763	pulse pressure measurement
EFO:0006336	diastolic blood pressure
EFO:0006312	mitochondrial DNA measurement
EFO:0008328	chronotype measurement
EFO:0010403	triacylglycerol 48:0 measurement
EFO:1001976	cardioembolic stroke
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007828	daytime rest measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D002819	Chorea	C10.228.662.262.249; C10.597.350.250; C23.888.592.350.250
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
D009069	Movement Disorders	C10.228.662

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4742 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

1 measured of 5 human assays (5 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
3-chloranyl-N-(3-morpholin-4-ylpropyl)-6-nitro-1-benzothiophene-2-carboxamide	EC50	950 nM

ChEMBL bioactivities

8 potent at pChembl≥5 of 28 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.43	EC50	3700	nM	CHEMBL536731
5.26	EC50	5500	nM	CHEMBL537639
5.25	EC50	5600	nM	CHEMBL536963
5.21	EC50	6200	nM	CHEMBL3216194
5.21	EC50	6100	nM	CHEMBL537413
5.21	EC50	6100	nM	CHEMBL559378
5.09	EC50	8200	nM	CHEMBL536499
5.00	EC50	1.01e+04	nM	CHEMBL194324

PubChem BioAssay actives

7 with measured affinity, of 72 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
4-pentadecylpiperazin-1-amine;hydrochloride	254630: Concentration required to stimulate binding of [35S]GTP-gamma-S, with G alpha o1	ec50	3.7000	uM
1-(2-formamidoethyl)-N-pentadecylpiperidine-4-carboxamide;hydrochloride	254630: Concentration required to stimulate binding of [35S]GTP-gamma-S, with G alpha o1	ec50	5.5000	uM
1-(4-piperidin-4-ylpiperidin-1-yl)pentadecan-1-one;hydrochloride	254630: Concentration required to stimulate binding of [35S]GTP-gamma-S, with G alpha o1	ec50	5.6000	uM
1-[4-(2-piperidin-4-ylethyl)piperidin-1-yl]pentadecan-1-one;hydrochloride	254630: Concentration required to stimulate binding of [35S]GTP-gamma-S, with G alpha o1	ec50	6.1000	uM
N-pentadecylpiperazin-1-amine;hydrochloride	254630: Concentration required to stimulate binding of [35S]GTP-gamma-S, with G alpha o1	ec50	6.1000	uM
1-pentadecyl-4-piperidin-4-ylpiperidine;dihydrochloride	254630: Concentration required to stimulate binding of [35S]GTP-gamma-S, with G alpha o1	ec50	6.2000	uM
N-pentadecylpiperidine-4-carboxamide;hydrochloride	254630: Concentration required to stimulate binding of [35S]GTP-gamma-S, with G alpha o1	ec50	8.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
pentanal	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	increases expression, affects cotreatment	1
Air Pollutants, Occupational	increases expression	1
Aldehydes	increases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Cadmium	decreases expression	1
Cannabidiol	affects cotreatment, decreases expression	1
Cocaine	decreases expression	1
Cuprizone	affects cotreatment, decreases expression, increases expression	1
Diazinon	increases methylation	1

ChEMBL screening assays

12 unique, capped per target: 10 functional, 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032494	Functional	Activation of human Go protein alpha subunit expressed in Escherichia coli assessed as protein bound [35S]GTPgammaS levels at 100 uM by scintillation spectroscopy	[35S]GTP gamma S binding studies of amphiphilic drugs-activated Gi proteins: a caveat. — Bioorg Med Chem Lett
CHEMBL4191673	Binding	Binding affinity to Galphao (unknown origin) assessed as change in melting temperature by differential scanning fluorimetry	Natural Products Discovered in a High-Throughput Screen Identified as Inhibitors of RGS17 and as Cytostatic and Cytotoxic Agents for Lung and Prostate Cancer Cell Lines. — J Nat Prod

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01662414	PHASE4	COMPLETED	Effect of Undenatured Cysteine-Rich Whey Protein Isolate (HMS 90®) in Patients With Parkinson’s Disease
NCT04871464	PHASE4	UNKNOWN	Role and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson’s Disease
NCT06710574	PHASE4	RECRUITING	Multimodal Image Technologies Investigate the Role and Mechanism of Probiotics in Improving RBD with Parkinson’s Disease
NCT01838278	PHASE3	UNKNOWN	Effectiveness of Vojta Therapy in Motor Development of Preterm Children
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06412653	PHASE2	COMPLETED	Prospective Pilot Trial to Address Feasibility and Safety of Oral Zinc in GNAO1 Associated Disorders
NCT00001929	PHASE2	COMPLETED	Treatment of Parkinson’s Disease With Eliprodil
NCT00331669	PHASE2	UNKNOWN	Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia
NCT00406029	PHASE2	COMPLETED	Dyskinesia in Parkinson’s Disease (Study P04501)
NCT00537017	PHASE2	COMPLETED	Follow Up Safety Study of SCH 420814 in Subjects With Parkinson’s Disease (P05175)
NCT00693472	PHASE2	TERMINATED	Study of Preladenant for the Treatment of Neuroleptic Induced Akathisia (Study P05145)
NCT01385592	PHASE2	COMPLETED	Evaluation of the Efficacy and Safety of AFQ056 in Parkinson’s Patients With L-dopa Induced Dyskinesias
NCT01491529	PHASE2	COMPLETED	Evaluation of the Efficacy and Safety of Modified Release AFQ056 in Parkinson’s Patients With L-dopa Induced Dyskinesias
NCT01491932	PHASE2	COMPLETED	Open-label, Long-term Safety Extension Study of AFQ056 in Parkinson’s Patients With L-dopa Induced Dyskinesias
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT04536987	PHASE2	COMPLETED	Robot Therapy for Rehabilitation of Hand Movement After Stroke
NCT04912115	PHASE2	SUSPENDED	Randomized, Double-Blind, Active Placebo-Controlled Study of Ketamine to Treat Levodopa-Induced Dyskinesia
NCT05636852	PHASE2	TERMINATED	Altropane Dose for Imaging Patients With Suspected Parkinson’s Disease
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT00001663	PHASE1	COMPLETED	Treatment of Cortical Myoclonus With Repetitive Transcranial Magnetic Stimulation
NCT02589340	PHASE1	TERMINATED	Buspirone, in Combination With Amantadine, for the Treatment of Levodopa-induced Dyskinesia
NCT03065192	PHASE1	COMPLETED	Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson’s Disease
NCT07232147	PHASE1	NOT_YET_RECRUITING	Clinical Research on Stem Cell Therapy for Parkinson’s Disease
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT00036296	PHASE1/PHASE2	COMPLETED	Effects of Talampanel on Patients With Advanced Parkinson’s Disease
NCT00037167	PHASE1/PHASE2	COMPLETED	Effects of Exercise Poles on Older Adults During Exercise Walking
NCT03295786	PHASE1/PHASE2	COMPLETED	Clinical Study to Test the Safety of CDNF by Brain Infusion in Patients With Parkinson’s Disease
NCT03775538	PHASE1/PHASE2	COMPLETED	Safety of CDNF by Brain Infusion in Patients With Parkinson’s Disease. Extension to HP-CD-CL-2002 Clinical Study
NCT04228653	PHASE1/PHASE2	UNKNOWN	Long-Term Follow-up Safety After DDS Implantation With/Without CDNF Infusions
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT00500994	EARLY_PHASE1	COMPLETED	Neurobiology of Functional Movement Disorder and Non-Epileptic Seizures
NCT00001208	Not specified	RECRUITING	Botulinum Toxin for the Treatment of Involuntary Movement Disorders
NCT00001252	Not specified	RECRUITING	Human Movement Database
NCT00001324	Not specified	COMPLETED	PET Scan to Study Brain Control of Human Movement
NCT00001361	Not specified	COMPLETED	Magnetic Resonance Imaging Studies of Motor and Thought Processes