GNAO1 (G protein subunit alpha o1)

Gene

• Entrez ID: 2775
• Gene name: G protein subunit alpha o1
• Gene symbol: GNAO1
• Synonyms (NCBI Gene): DEE17, EIEE17, G-ALPHA-o, GNAO, HG1G, HLA-DQB1, NEDIM
• Chromosome: 16
• Chromosome location: 16q13
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587777054	T>A	Pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant
rs587777055	A>G	Pathogenic	Missense variant, coding sequence variant
rs587777056	CATTCAAGAACCTCCACTTCA>-	Pathogenic	Inframe deletion, coding sequence variant
rs587777057	G>A,C	Pathogenic	Missense variant, coding sequence variant
rs797044878	G>A,T	Uncertain-significance, likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs797044951	G>A,C	Pathogenic, likely-pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs878853051	A>G	Likely-pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant
rs886039494	C>G,T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs1057518440	C>A	Pathogenic	Coding sequence variant, missense variant
rs1057518678	A>G	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs1064794533	G>A	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs1064795384	T>A	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant
rs1064797211	GT>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1085307876	G>A	Pathogenic	Genic downstream transcript variant, intron variant
rs1085307894	A>C	Pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant
rs1085307932	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1114167431	A>G	Pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant
rs1555507477	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1555507479	C>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1555508316	T>C	Pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant
rs1567488305	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1596867702	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1596871452	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1596872804	G>A	Pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1023483	hsa-miR-1231	CLIP-seq
MIRT1023484	hsa-miR-1285	CLIP-seq
MIRT1023485	hsa-miR-151-3p	CLIP-seq
MIRT1023486	hsa-miR-3119	CLIP-seq
MIRT1023487	hsa-miR-3150a-3p	CLIP-seq
MIRT1023488	hsa-miR-3175	CLIP-seq
MIRT1023489	hsa-miR-3184	CLIP-seq
MIRT1023490	hsa-miR-3187-5p	CLIP-seq
MIRT1023491	hsa-miR-34a	CLIP-seq
MIRT1023492	hsa-miR-34c-5p	CLIP-seq
MIRT1023493	hsa-miR-378g	CLIP-seq
MIRT1023494	hsa-miR-411	CLIP-seq
MIRT1023495	hsa-miR-423-5p	CLIP-seq
MIRT1023496	hsa-miR-4302	CLIP-seq
MIRT1023497	hsa-miR-4463	CLIP-seq
MIRT1023498	hsa-miR-4486	CLIP-seq
MIRT1023499	hsa-miR-4499	CLIP-seq
MIRT1023500	hsa-miR-449a	CLIP-seq
MIRT1023501	hsa-miR-449b	CLIP-seq
MIRT1023502	hsa-miR-4651	CLIP-seq
MIRT1023503	hsa-miR-4662a-3p	CLIP-seq
MIRT1023504	hsa-miR-4728-5p	CLIP-seq
MIRT1023505	hsa-miR-491-5p	CLIP-seq
MIRT1023506	hsa-miR-608	CLIP-seq
MIRT1023507	hsa-miR-612	CLIP-seq
MIRT1023508	hsa-miR-939	CLIP-seq
MIRT1023509	hsa-miR-1254	CLIP-seq
MIRT1023510	hsa-miR-1291	CLIP-seq
MIRT1023511	hsa-miR-21	CLIP-seq
MIRT1023512	hsa-miR-214	CLIP-seq
MIRT1023513	hsa-miR-2277-3p	CLIP-seq
MIRT1023514	hsa-miR-2355-5p	CLIP-seq
MIRT1023515	hsa-miR-3064-5p	CLIP-seq
MIRT1023516	hsa-miR-3116	CLIP-seq
MIRT1023517	hsa-miR-328	CLIP-seq
MIRT1023518	hsa-miR-3619-5p	CLIP-seq
MIRT1023519	hsa-miR-3660	CLIP-seq
MIRT1023520	hsa-miR-370	CLIP-seq
MIRT1023521	hsa-miR-4269	CLIP-seq
MIRT1023522	hsa-miR-4270	CLIP-seq
MIRT1023523	hsa-miR-4441	CLIP-seq
MIRT1023524	hsa-miR-4526	CLIP-seq
MIRT1023525	hsa-miR-4529-5p	CLIP-seq
MIRT1023526	hsa-miR-4645-5p	CLIP-seq
MIRT1023527	hsa-miR-4673	CLIP-seq
MIRT1023528	hsa-miR-4687-3p	CLIP-seq
MIRT1023529	hsa-miR-4718	CLIP-seq
MIRT1023530	hsa-miR-590-5p	CLIP-seq
MIRT1023531	hsa-miR-596	CLIP-seq
MIRT1023532	hsa-miR-637	CLIP-seq
MIRT1023533	hsa-miR-661	CLIP-seq
MIRT1023534	hsa-miR-761	CLIP-seq
MIRT1023535	hsa-miR-873	CLIP-seq
MIRT1023485	hsa-miR-151-3p	CLIP-seq
MIRT1023491	hsa-miR-34a	CLIP-seq
MIRT1023492	hsa-miR-34c-5p	CLIP-seq
MIRT1023494	hsa-miR-411	CLIP-seq
MIRT1023496	hsa-miR-4302	CLIP-seq
MIRT1023497	hsa-miR-4463	CLIP-seq
MIRT1023499	hsa-miR-4499	CLIP-seq
MIRT1023500	hsa-miR-449a	CLIP-seq
MIRT1023501	hsa-miR-449b	CLIP-seq
MIRT1023503	hsa-miR-4662a-3p	CLIP-seq
MIRT2236340	hsa-miR-587	CLIP-seq
MIRT2236341	hsa-miR-885-5p	CLIP-seq
MIRT2540081	hsa-miR-1271	CLIP-seq
MIRT2540082	hsa-miR-182	CLIP-seq
MIRT2540083	hsa-miR-433	CLIP-seq
MIRT2540084	hsa-miR-4470	CLIP-seq
MIRT2540085	hsa-miR-96	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003924	Function	GTPase activity	IBA
GO:0003924	Function	GTPase activity	IEA
GO:0003924	Function	GTPase activity	TAS	1899283
GO:0003925	Function	G protein activity	IEA
GO:0003925	Function	G protein activity	ISS
GO:0005515	Function	Protein binding	IPI	17500595, 32814053, 33961781, 34685729, 37207277, 37776851
GO:0005525	Function	GTP binding	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005834	Component	Heterotrimeric G-protein complex	IBA
GO:0005834	Component	Heterotrimeric G-protein complex	IDA	29925951
GO:0005886	Component	Plasma membrane	IDA	34685729
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006904	Process	Vesicle docking involved in exocytosis	IEA
GO:0006936	Process	Muscle contraction	TAS	9050846
GO:0007165	Process	Signal transduction	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	IBA
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	IEA
GO:0007193	Process	Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IDA	33408414
GO:0007198	Process	Adenylate cyclase-inhibiting serotonin receptor signaling pathway	IDA	29925951
GO:0007212	Process	G protein-coupled dopamine receptor signaling pathway	IBA
GO:0007212	Process	G protein-coupled dopamine receptor signaling pathway	IEA
GO:0007626	Process	Locomotory behavior	IEA
GO:0008016	Process	Regulation of heart contraction	IEA
GO:0010854	Function	Adenylate cyclase regulator activity	ISS
GO:0016020	Component	Membrane	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0019001	Function	Guanyl nucleotide binding	IEA
GO:0030425	Component	Dendrite	IEA
GO:0031683	Function	G-protein beta/gamma-subunit complex binding	IBA
GO:0031683	Function	G-protein beta/gamma-subunit complex binding	IEA
GO:0031821	Function	G protein-coupled serotonin receptor binding	IBA
GO:0031852	Function	Mu-type opioid receptor binding	IBA
GO:0042734	Component	Presynaptic membrane	IEA
GO:0044297	Component	Cell body	IEA
GO:0045211	Component	Postsynaptic membrane	IEA
GO:0046676	Process	Negative regulation of insulin secretion	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0051430	Function	Corticotropin-releasing hormone receptor 1 binding	IBA
GO:0098688	Component	Parallel fiber to Purkinje cell synapse	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0098982	Component	GABA-ergic synapse	IEA
GO:0099170	Process	Postsynaptic modulation of chemical synaptic transmission	IEA

Other IDs

• MIM: 139311
• HGNC: 4389
• e!Ensembl: ENSG00000087258

Protein

• UniProt ID: P09471
• Protein name: Guanine nucleotide-binding protein G(o) subunit alpha (EC 3.6.5.-)
• Protein function: Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades (PubMed:29925951, PubMed:33408414). The alpha chain contains the guanine nucleotide binding
• PDB: 6FUF, 6G79, 6K41, 6OIK, 6WWZ, 7D76, 7D77, 7EJ0, 7EJ8, 7EJA, 7EJK, 7QVM, 7T8X, 7T90, 7T94, 7T96, 7W2Z, 7W6P, 7W7E, 7XJJ, 7Y24, 8DZQ, 8E9X, 8FN1, 8HPT, 8HQC, 8I95, 8I97, 8I9L, 8I9S, 8IA2, 8IEC, 8IED, 8IY9, 8IYH, 8IYW, 8J6D, 8JER, 8JHN, 8JZP, 8JZZ, 8TZQ, 8U02, 8XWV, 8XX3, 8XX6, 8XX7, 8XXH, 8XXR, 8XXX, 8XXZ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00503	G-alpha	13 → 343	G-protein alpha subunit	Domain

• Sequence:

  MGCTLSAEERAALERSKAIEKNLKEDGISAAKDVKLLLLGAGESGKSTIVKQMKIIHEDG
  FSGEDVKQYKPVVYSNTIQSLAAIVRAMDTLGIEYGDKERKADAKMVCDVVSRMEDTEPF
  SAELLSAMMRLWGDSGIQECFNRSREYQLNDSAKYYLDSLDRIGAADYQPTEQDILRTRV
  KTTGIVETHFTFKNLHFRLFDVGGQRSERKKWIHCFEDVTAIIFCVALSGYDQVLHEDET
  TNRMHESLMLFDSICNNKFFIDTSIILFLNKKDLFGEKIKKSPLTICFPEYTGPNTYEDA
  AAYIQAQFESKNRSPNKEIYCHMTCATDTNNIQVVFDAVTDIIIANNLRGCGLY

• Sequence length: 354

Pathways

KEGG:

Rap1 signaling pathway
Hormone signaling
Circadian entrainment
Retrograde endocannabinoid signaling
Glutamatergic synapse
Cholinergic synapse
Serotonergic synapse
GABAergic synapse
Dopaminergic synapse
Long-term depression
Estrogen signaling pathway
Melanogenesis
Oxytocin signaling pathway
Relaxin signaling pathway
Morphine addiction
Alcoholism
Chagas disease
Toxoplasmosis
Human cytomegalovirus infection
Human immunodeficiency virus 1 infection

Reactome:

PLC beta mediated events
G-protein activation
Ca2+ pathway
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Abnormality of the nervous system	Pathogenic	rs797044951, rs587777057	RCV001814097 RCV001814039
Chorea	Likely pathogenic; Pathogenic	rs1064794533, rs1596871452	RCV001003613 RCV001003611
Choreoathetosis	Pathogenic	rs1596872804	RCV001003614
Developmental and epileptic encephalopathy	Pathogenic; Likely pathogenic	rs2037920369, rs2143705016, rs2143272260, rs2143647375, rs2143664797, rs2143664808, rs1297225571, rs2143272046, rs758779535, rs797044878, rs797044951, rs797045599, rs2506531670, rs869312939, rs886039494, rs886041766, rs886041715, rs2506858241, rs2506876806, rs2506872240, rs2037920694, rs2543427284, rs1064794533, rs1064795384, rs1085307876, rs1555507477, rs1555499800, rs1596787821, rs587777057, rs1596872804, rs2037920791, rs2037724743, rs2143272162	RCV001315820 RCV001972962 RCV001889307 RCV001976534 RCV001949659 RCV001994745 RCV002002430 RCV001877856 RCV001941166 RCV003074982 RCV001065368 RCV001857676 RCV000694174 RCV003043124 RCV001378535 RCV000475848 RCV002519057 RCV000688464 RCV003589834 RCV003590213 RCV003590367 RCV003590471 RCV003754336 RCV003754354 RCV001851189 RCV001851218 RCV001851316 RCV000699557 RCV000806364 RCV002524192 RCV000636427 RCV000794940 RCV000468248 RCV002549730 RCV001862728 RCV001068363 RCV001065180 RCV001224759 RCV005094377
Developmental and epileptic encephalopathy, 1	Likely pathogenic	rs886041766	RCV000714659
Developmental and epileptic encephalopathy, 17	Pathogenic; Likely pathogenic	rs2143272046, rs2143664881, rs1114167431, rs2143664861, rs1057518440, rs2543427201, rs2506529308, rs886041766, rs2543432175, rs797044878, rs797045599, rs2506529438, rs886039494, rs886041715, rs869312939, rs2543432234, rs1057518678, rs1064794533, rs1085307876, rs1555499800, rs1555508316, rs1596787821, rs797044951, rs587777054, rs587777055, rs587777056, rs587777057, rs1596867702, rs2506871916, rs2037919953, rs2143272162, rs2143660403, rs546569747, rs2143699686, rs2143699701	RCV002246570 RCV002249062 RCV002249063 RCV002250020 RCV002250021 RCV002290360 RCV003230749 RCV003230750 RCV002471735 RCV005410892 RCV000193275 RCV003224928 RCV001775107 RCV005230223 RCV005410965 RCV004547411 RCV000414910 RCV000762965 RCV002466519 RCV000655933 RCV000499510 RCV000590935 RCV002272357 RCV000824830 RCV000850558 RCV000056405 RCV000056406 RCV000056407 RCV000056408 RCV000989602 RCV000989603 RCV000989604 RCV001004674 RCV001089718 RCV001580365 RCV001580367 RCV001580366 RCV001580369 RCV001580370
Developmental delay	Pathogenic	rs797044951	RCV001580372
Dyskinesia	Likely pathogenic; Pathogenic	rs1064794533, rs1596871452	RCV001003613 RCV001003611
Genetic developmental and epileptic encephalopathy	Likely pathogenic; Pathogenic	rs797045599	RCV005625426
GNAO1-related developmental delay-seizures-movement disorder spectrum	Pathogenic; Likely pathogenic	rs797044951, rs2143699701	RCV003996903 RCV005232257
GNAO1-related disorder	Pathogenic; Likely pathogenic	rs886039494, rs1064794533, rs1085307876, rs886041715, rs587777057	RCV003401217 RCV005230943 RCV003900029 RCV005870916 RCV003421966
GNAO1-Related Neurodevelopmental Disorder	Pathogenic	rs587777057	RCV005229879
Microcephaly	Pathogenic	rs587777057	RCV001252685
Movement disorder	Pathogenic; Likely pathogenic	rs886039494, rs2037743862	RCV001003612 RCV003484997
Neurodevelopmental disorder with involuntary movements	Pathogenic; Likely pathogenic	rs2143665312, rs2143699753, rs2143272172, rs2543432061, rs797044878, rs797044951, rs797045599, rs2143272046, rs2506529438, rs886039494, rs2506529268, rs869312939, rs2543432234, rs1057518678, rs1064794533, rs1085307876, rs1114167431, rs1555499800, rs1555507479, rs886041766, rs587777055, rs587777057, rs2143660403, rs546569747, rs2143699686, rs2143699701	RCV001374408 RCV001730048 RCV001823038 RCV002287869 RCV000490633 RCV000490631 RCV000762964 RCV003223534 RCV003224928 RCV000490628 RCV003335829 RCV005410965 RCV004547411 RCV001580371 RCV000762965 RCV001291829 RCV000490630 RCV000490634 RCV003458445 RCV000626015 RCV000714660 RCV000850558 RCV002281559 RCV000762963 RCV001580367 RCV001580366 RCV001580369 RCV001580370
Rare genetic intellectual disability	Pathogenic	rs587777057	RCV001256978

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Epileptic encephalopathy	Conflicting classifications of pathogenicity	rs886041715	RCV001003610
Familial cancer of breast	Benign; Likely benign	rs199741926	RCV005899567
Intellectual disability	Benign; Likely benign	rs559674838, rs372787855	RCV001252009 RCV005626245
Malignant tumor of esophagus	Benign; Likely benign	rs199741926	RCV005899568
Melanoma	Benign; Likely benign	rs199741926	RCV005899569
See cases	Uncertain significance	rs2143270534	RCV002253122
Seizure	Conflicting classifications of pathogenicity	rs2143704776	RCV001507300
Thyroid cancer, nonmedullary, 1	Likely benign	rs770769352	RCV005931648

Associations from Text Mining
Disease Name	Relationship Type	References
Adenocarcinoma	Associate	28350845
Atrial Fibrillation	Associate	37960721
Autism Spectrum Disorder	Associate	22965006
Brain Diseases	Associate	25014031, 27072799, 27476654, 28747448, 28817111, 30682224, 34685729, 35722775, 36980817, 37001522, 37887313
Breast Neoplasms	Associate	26894955
Carcinogenesis	Associate	23984917, 28350845
Carcinoma Hepatocellular	Associate	23984917
Carcinoma Hepatocellular	Inhibit	34900204
Carcinoma Renal Cell	Associate	26043775
Cerebral Palsy	Associate	35076175, 37034444
Chorea	Associate	35722775, 36054588
Cognition Disorders	Associate	27072799
Colitis	Associate	35725943
Colorectal Neoplasms	Inhibit	29381923
Colorectal Neoplasms	Associate	30987631
Developmental Disabilities	Associate	27072799, 27343026, 30682224, 34685729, 36980817, 37887313
Disease	Associate	30682224, 34685729
Dyskinesia Drug Induced	Associate	30682224
Dyskinesias	Associate	27072799
Dystonia	Associate	35722775, 37034444
Dystonia Dopa responsive	Associate	37034444
Epilepsy	Associate	28747448, 34685729, 36980817, 37001522
Epileptic Encephalopathy Early Infantile 3	Associate	37482918, 37867425, 37887313
Hyperkinesis	Associate	24982418, 36054588
Immunologic Deficiency Syndromes	Inhibit	36980817
Infant Newborn Diseases	Associate	28817111
Infantile Epileptic Dyskinetic Encephalopathy	Associate	28747448
Intellectual Disability	Associate	27072799, 34685729
Language Development Disorders	Associate	36980817
Lesch Nyhan Syndrome	Associate	33875724
Lymphatic Metastasis	Associate	34900204
Motor Disorders	Associate	37001522, 37887313
Movement Disorders	Associate	27072799, 28747448, 30682224, 33446253, 34685729, 35722775, 36980817
Muscle Hypotonia	Associate	30682224
Neoplasms	Associate	24982418
Neurodegenerative Diseases	Associate	34685729
Pseudohypoparathyroidism	Associate	24982418
Rhabdomyolysis	Associate	35725943
Seizures	Associate	27072799, 28747448, 30682224, 35305402, 37887313
Spasms Infantile	Associate	31394400
Storm Syndrome	Associate	35725943
Teratozoospermia	Associate	29901159
Vision Disorders	Associate	36980817