ArticleHuman molecular genetics2022
Genetic modeling of GNAO1 disorder delineates mechanisms of Gαo dysfunction.
Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Longitudinal Phenotypic Trajectories in GNAO1-Related Disorders: Defining Disease Progression and Clinical Profiles.Annals of neurology · 2026Article
- G-protein regulatory network governs receptor internalization dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Beyond GH stimulation tests: genetic heterogeneity and treatment response in children with diagnosed GH deficiency.Journal of the Endocrine Society · 2026Article
- Dissecting GPCR Contributions to Gαo-Dependent Motor Dysfunction inBiomedicines · 2026Article
- G protein regulatory network shapes magnitude and kinetics of behavioral responses in an engineered opioid receptor model.The Journal of biological chemistry · 2026Article
- Deciphering a mechanistic basis for the pathological effect of the GNAO1 E246K variant in neurodevelopmental disorder.BBA advances · 2026Article
- Article
- Episodic Choreo-Dystonic Storm in an Infantile-Onset Movement Disorder: Think of G Protein Subunit Alpha O1 Gene Defect!Annals of Indian Academy of Neurology · 2025Article
- Dominant Gα mutations in human disease: unifying mechanisms and treatment strategies.EMBO molecular medicine · 2025Review
- Personalized allele-specific antisense oligonucleotides for GNAO1-neurodevelopmental disorder.Molecular therapy. Nucleic acids · 2025Article
- Article
- Decoding GNAO1 mutations usingFrontiers in cellular neuroscience · 2025Review
- GPCR-G protein selectivity revealed by structural pharmacology.The FEBS journal · 2024Review
- Neomorphic Gαo mutations gain interaction with Ric8 proteins in GNAO1 encephalopathies.The Journal of clinical investigation · 2024Article
- Article
- The Schwann cell-specific G-protein Gαo (Gnao1) is a cell-intrinsic controller contributing to the regulation of myelination in peripheral nerve system.Acta neuropathologica communications · 2024Article
- Dyskinetic crisis inFrontiers in neurology · 2024Article
- Matching variants for functional characterization of genetic variants.G3 (Bethesda, Md.) · 2023Article
- Severity of GNAO1-Related Disorder Correlates with Changes in G-Protein Function.Annals of neurology · 2023Observational
- Back to the future through the wormhole: Caenorhabditis elegans as a preclinical model.Disease models & mechanisms · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
GNAO1 encephalopathy is a neurodevelopmental disorder with a spectrum of symptoms that include dystonic movements, seizures and developmental delay. While numerous GNAO1 mutations are associated with this disorder, the functional consequences of pathological variants are not completely understood. Here, we deployed the invertebrate C. elegans as a whole-animal behavioral model to study the functional effects of GNAO1 disorder-associated mutations. We tested several pathological GNAO1 mutations for effects on locomotor behaviors using a combination of CRISPR/Cas9 gene editing and transgenic overexpression in vivo. We report that all three mutations tested (G42R, G203R and R209C) result in strong loss of function defects when evaluated as homozygous CRISPR alleles. In addition, mutations produced dominant negative effects assessed using both heterozygous CRISPR alleles and transgenic overexpression. Experiments in mice confirmed dominant negative effects of GNAO1 G42R, which impaired numerous motor behaviors. Thus, GNAO1 pathological mutations result in conserved functional outcomes across animal models. Our study further establishes the molecular genetic basis of GNAO1 encephalopathy, and develops a CRISPR-based pipeline for functionally evaluating mutations associated with neurodevelopmental disorders.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.