GNAO1

Chr 16AD

G protein subunit alpha o1

Also known as: DEE17, EIEE17, G-ALPHA-o, GNAO, HG1G, NEDIM

NCBI Gene: 2775ENSG00000087258UniProt: P09471

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. [provided by RefSeq, Aug 2015]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 17MIM #615473
AD
Neurodevelopmental disorder with involuntary movementsMIM #617493
AD
293
ClinVar variants
48
Pathogenic / LP
0.99
pLI score· haploinsufficient
2
Active trials
Clinical Summary— GNAO1
🧬
Gene-Disease Validity (ClinGen)
movement disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
48 Pathogenic / Likely Pathogenic· 127 VUS of 293 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.26LOEUF
pLI 0.990
Z-score 3.73
OE 0.06 (0.02–0.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.19Z-score
OE missense 0.41 (0.34–0.48)
93 obs / 228.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.02–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.41 (0.34–0.48)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.90
0≤1.21.6
LoF obs/exp: 1 / 18.1Missense obs/exp: 93 / 228.9Syn Z: 0.77

ClinVar Variant Classifications

293 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic24
VUS127
Likely Benign107
Benign4
Conflicting7
24
Pathogenic
24
Likely Pathogenic
127
VUS
107
Likely Benign
4
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
11
10
0
24
Likely Pathogenic
5
14
5
0
24
VUS
2
112
13
0
127
Likely Benign
0
10
44
53
107
Benign
0
0
4
0
4
Conflicting
—7
Total101477653293

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GNAO1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

GNAO1-related epileptic encephalopathy

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 17

MIM #615473

Molecular basis of disorder known

Autosomal dominant

Neurodevelopmental disorder with involuntary movements

MIM #617493

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — GNAO1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Genetic Landscape of Complex Childhood-Onset Hyperkinetic Movement Disorders.
Pérez-Dueñas B et al.·Mov Disord
2022
Chorea.
Termsarasab P·Continuum (Minneap Minn)
2019Review
GNAO1-related movement disorder: An update on phenomenology, clinical course, and response to treatments.
Novelli M et al.·Parkinsonism Relat Disord
2023Review
Clinical and Molecular Profiling in GNAO1 Permits Phenotype-Genotype Correlation.
Lasa-Aranzasti A et al.·Mov Disord
2024
Phenotypic Diversity in GNAO1 Patients: A Comprehensive Overview of Variants and Phenotypes.
Sáez González M et al.·Hum Mutat
2023Review
Deep Brain Stimulation for GNAO1-Associated Dystonia: A Systematic Review and Meta-Analysis.
Decraene B et al.·Neuromodulation
2024Meta-analysis
A mechanistic review on GNAO1-associated movement disorder.
Feng H et al.·Neurobiol Dis
2018Review
Phenomenology and clinical course of movement disorder in GNAO1 variants: Results from an analytical review.
Schirinzi T et al.·Parkinsonism Relat Disord
2019Review
[Encephalopathy GNAO1].
Bobylova MY et al.·Zh Nevrol Psikhiatr Im S S Korsakova
2023
Molecular annotation of G protein variants in a neurological disorder.
Knight KM et al.·Cell Rep
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
GNAO1EpilepsyHyperkinesis

Tianasen (ASO-GNAO1) for GNAO1-Encephalopathy With Epilepsy and Movement Disorders.

RECRUITING
NCT07363603Phase PHASE1, PHASE2Pirogov Russian National Research Medical UniversityStarted 2025-09-09
Antisense oligonucleotide treatment (ASO)
DystoniaMovement DisordersCombined Dystonia

Long-read Genome Sequencing for the Molecular Diagnosis of Dystonia

NOT YET RECRUITING
NCT06999096Phase NAUniversity Hospital, Strasbourg, FranceStarted 2025-08
Long-read whole genome sequencing

External Resources

Links to major genomics databases and tools