GNAO1

G protein subunit alpha o1, the group of G protein subunits alpha, group i|MicroRNA protein coding host genes

Basic information

Region (hg38): 16:56189660-56357444

Links

ENSG00000087258 ∙ NCBI:2775 ∙ OMIM:139311 ∙ HGNC:4389 ∙ Uniprot:P09471 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 17 (Strong), mode of inheritance: AD
• movement disorder (Definitive), mode of inheritance: AD
• genetic developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD
• movement disorder (Definitive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 17 (Strong), mode of inheritance: AD
• neurodevelopmental disorder with involuntary movements (Strong), mode of inheritance: AD
• genetic developmental and epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 17 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 17; Neurodevelopmental disorder with involuntary movements	AD	Neurologic	In Neurodevelopmental disorder with involuntary movements (NEDIM), specific medications (eg, topiramate) have been reported in some individuals as beneficial for treatment of the movement disorder	Neurologic	23993195; 25966631; 26060304; 27068059; 27625011; 27916449; 28357411

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GNAO1 gene.

• Early-infantile_DEE (317 variants)
• not_provided (166 variants)
• Developmental_and_epileptic_encephalopathy,_17 (65 variants)
• Inborn_genetic_diseases (64 variants)
• Developmental_and_epileptic_encephalopathy (49 variants)
• Neurodevelopmental_disorder_with_involuntary_movements (48 variants)
• GNAO1-related_disorder (22 variants)
• not_specified (13 variants)
• GNAO1-related_developmental_delay-seizures-movement_disorder_spectrum (2 variants)
• Chorea (2 variants)
• Intellectual_disability (2 variants)
• Movement_disorder (2 variants)
• Abnormality_of_the_nervous_system (2 variants)
• Dyskinesia (2 variants)
• Epileptic_encephalopathy (1 variants)
• Microcephaly (1 variants)
• Developmental_delay (1 variants)
• See_cases (1 variants)
• Rare_genetic_intellectual_disability (1 variants)
• Choreoathetosis (1 variants)
• Genetic_developmental_and_epileptic_encephalopathy (1 variants)
• GNAO1-Related_Neurodevelopmental_Disorder (1 variants)
• Seizure (1 variants)
• Developmental_and_epileptic_encephalopathy,_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNAO1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020988.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	116	2	120
missense	37	51	133	26	1	248
nonsense	1	1	1			3
start loss						0
frameshift	3	2	1			6
splice donor/acceptor (+/-2bp)	3	5	3			11
Total	44	59	140	142	3

Highest pathogenic variant AF is 0.000006569094

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNAO1	protein_coding	protein_coding	ENST00000262494	8	166055

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125744	0	3	125747	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.19	93	229	0.406	0.0000142	2343
Missense in Polyphen		33	95.675	0.34492		988
Synonymous	0.771	86	95.6	0.900	0.00000683	648
Loss of Function	3.73	1	18.1	0.0551	9.38e-7	209

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(o) protein function is not clear. Stimulated by RGS14.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 17 (EIEE17) [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. {ECO:0000269|PubMed:23993195, ECO:0000269|PubMed:25966631, ECO:0000269|PubMed:26485252, ECO:0000269|PubMed:27476654, ECO:0000269|PubMed:27864847}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:25966631, ECO:0000269|PubMed:26060304, ECO:0000269|PubMed:27068059, ECO:0000269|PubMed:27625011, ECO:0000269|PubMed:28357411}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Relaxin signaling pathway - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Long-term depression - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Alcoholism - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human Thyroid Stimulating Hormone (TSH) signaling pathway;Corticotropin-releasing hormone signaling pathway;G Protein Signaling Pathways;Calcium Regulation in the Cardiac Cell;Serotonin HTR1 Group and FOS Pathway;Signaling by GPCR;Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding;Signaling by WNT;Signal Transduction;Metabolism of proteins;Chaperonin-mediated protein folding;CRH;S1P5 pathway;Ca2+ pathway;Beta-catenin independent WNT signaling;CXCR4-mediated signaling events;Protein folding;G-protein activation;PLC beta mediated events;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;TSH;GPCR downstream signalling;PAR1-mediated thrombin signaling events;LPA receptor mediated events;S1P1 pathway;S1P3 pathway;CXCR3-mediated signaling events;S1P4 pathway;Plasma membrane estrogen receptor signaling;Nongenotropic Androgen signaling;Hedgehog signaling events mediated by Gli proteins;Sphingosine 1-phosphate (S1P) pathway;Endothelins;S1P2 pathway (Consensus)

Recessive Scores

• pRec: 0.179

Intolerance Scores

• rvis_EVS: -0.74
• rvis_percentile_EVS: 13.94

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.848

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: protein folding;muscle contraction;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;dopamine receptor signaling pathway;Wnt signaling pathway, calcium modulating pathway;aging;locomotory behavior;regulation of heart contraction;forebrain development;neuron projection development;response to cytokine;odontogenesis of dentin-containing tooth;response to hydrogen peroxide;response to morphine;positive regulation of GTPase activity;negative regulation of calcium ion transport
• Cellular component: heterotrimeric G-protein complex;plasma membrane;dendrite;myelin sheath;cell body
• Molecular function: G protein-coupled receptor binding;GTPase activity;GTP binding;G-protein beta/gamma-subunit complex binding;G protein-coupled serotonin receptor binding;mu-type opioid receptor binding;GTPase activating protein binding;metal ion binding;corticotropin-releasing hormone receptor 1 binding