GNAO1
Chr 16ADG protein subunit alpha o1
Also known as: DEE17, EIEE17, G-ALPHA-o, GNAO, HG1G, NEDIM
The protein encodes the alpha subunit of the Go heterotrimeric G-protein complex, which mediates signal transduction at the cell membrane. Mutations cause early-onset epileptic encephalopathy and neurodevelopmental disorders with involuntary movements through an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function variants, and mutations can cause disease through multiple mechanisms depending on the specific variant type.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Long-read Genome Sequencing for the Molecular Diagnosis of Dystonia
NOT YET RECRUITINGTianasen (ASO-GNAO1) for GNAO1-Encephalopathy With Epilepsy and Movement Disorders.
RECRUITINGExternal Resources
Links to major genomics databases and tools