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
• developmental and epileptic encephalopathy (Supportive), 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
• movement disorder (Definitive), mode of inheritance: AD
• developmental and epileptic encephalopathy (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 epileptic encephalopathy with suppression bursts (20 variants)
• not provided (11 variants)
• Developmental and epileptic encephalopathy, 17 (10 variants)
• Inborn genetic diseases (4 variants)
• Neurodevelopmental disorder with involuntary movements (4 variants)
• GNAO1-related disorder (2 variants)
• Developmental and epileptic encephalopathy, 17;Neurodevelopmental disorder with involuntary movements (2 variants)
• Abnormality of the nervous system (2 variants)
• GNAO1-related developmental delay-seizures-movement disorder spectrum (1 variants)
• Microcephaly (1 variants)
• Developmental delay (1 variants)
• Choreoathetosis (1 variants)
• Movement disorder (1 variants)
• Rare genetic intellectual disability (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				108	4	112
missense	25	37	94	15	4	175
nonsense	1		1	1		3
start loss						0
frameshift	2	2	1			5
inframe indel	1	3	2	1		7
splice donor/acceptor (+/-2bp)	2	3	1			6
splice region		1	9	14	2	26
non coding			4	64	33	101
Total	31	45	103	189	41

Variants in GNAO1

This is a list of pathogenic ClinVar variants found in the GNAO1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-56191028-G-A			Likely benign (Sep 29, 2018)
16-56191113-G-A			Benign (Jul 21, 2018)
16-56191124-G-A			Benign (Jul 31, 2018)
16-56191213-G-C			Likely benign (Aug 21, 2019)
16-56191219-G-T			Benign (Jul 26, 2018)
16-56192239-G-C		Neurodevelopmental disorder with involuntary movements	Likely pathogenic (Aug 17, 2023)
16-56192244-T-C		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Feb 27, 2023)
16-56192252-G-T		Developmental and epileptic encephalopathy, 17	Pathogenic (-)
16-56192256-A-G		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Jan 28, 2024)
16-56192256-AGAG-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Nov 24, 2023)
16-56192259-G-A		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Apr 24, 2020)
16-56192262-G-A		Early infantile epileptic encephalopathy with suppression bursts • Inborn genetic diseases • GNAO1-related disorder	Likely benign (Jan 22, 2024)
16-56192268-C-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Nov 16, 2022)
16-56192271-C-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Dec 06, 2022)
16-56192273-T-C			Likely pathogenic (Jul 01, 2020)
16-56192289-G-A		Early infantile epileptic encephalopathy with suppression bursts	Conflicting classifications of pathogenicity (Oct 16, 2023)
16-56192291-T-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Mar 26, 2022)
16-56192292-T-G		Developmental and epileptic encephalopathy, 17 • Developmental and epileptic encephalopathy, 17;Neurodevelopmental disorder with involuntary movements	Likely pathogenic (Feb 09, 2023)
16-56192293-G-A		Early infantile epileptic encephalopathy with suppression bursts • Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 22, 2022)
16-56192301-C-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Sep 12, 2017)
16-56192302-C-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Oct 07, 2022)
16-56192310-G-A		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Jan 19, 2024)
16-56192311-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Aug 16, 2022)
16-56192319-C-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Jun 20, 2023)
16-56192324-C-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jul 19, 2022)

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
0.990	0.0104	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

Haploinsufficiency Scores

• pHI: 0.248
• hipred: Y
• hipred_score: 0.825
• ghis: 0.705

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

Mouse Genome Informatics

• Gene name: Gnao1
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

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