ArticleMolecular genetics & genomic medicine2020
Haploinsufficiency as a disease mechanism in GNB1-associated neurodevelopmental disorder.
Article in Molecular genetics & genomic medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- Loss of expression and function of Gβγ by GNB1 encephalopathy-associated L95P mutation of the GβFrontiers in pharmacology · 2025Article
- G-Protein Signaling in Alzheimer's Disease: Spatial Expression Validation of Semi-supervised Deep Learning-Based Computational Framework.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Clinical characterization of familial 1p36.3 microduplication.Neurogenetics · 2023Article
- Article
- Article
- Motor, epileptic, and developmental phenotypes in genetic disorders affecting G protein coupled receptors-cAMP signaling.Frontiers in neurology · 2022Review
- Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.Nature genetics · 2021Article
- Subtype-dependent regulation of Gβγ signalling.Cellular signalling · 2021Review
- Case Report: A NovelFrontiers in neurology · 2021Article
- Haploinsufficiency as a disease mechanism in GNB1-associated neurodevelopmental disorder.Molecular genetics & genomic medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundGNB1 encodes a subunit of a heterotrimeric G-protein complex that transduces intracellular signaling cascades. Disruptions to the gene have previously been shown to be embryonic lethal in knockout mice and to cause complex neurodevelopmental disorders in humans. To date, the majority of variants associated with disease in humans have been missense variants in exons 5-7.
methodsGenetic sequencing was performed on two patients presenting with complex neurological phenotypes including intellectual disability, hypotonia, and in one patient seizures. Reported variants were assessed using RNA sequencing and functional BRET/BiFC assays.
resultsA splice variant reported in patient 1 was confirmed to cause usage of a cryptic splice site leading to a truncated protein product. Patient 2 was reported to have a truncating variant. BRET and BiFC assays of both patient variants confirmed both were deficient in inducing GPCR-induced G protein activation due to lack of dimer formation with the Gγ subunit.
conclusionHere, we report two patients with functionally confirmed loss of function variants in GNB1 and neurodevelopmental phenotypes including intellectual disability, hypotonia, and seizures in one patient. These results suggest haploinsufficiency of GNB1 is a mechanism for neurodevelopmental disorders in humans.
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.