ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
De novo missense variants in RAC3 cause a novel neurodevelopmental syndrome.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Epilepsy-associated digenic variants affecting an actin/mitochondria/glutamate pathway promote seizure susceptibility.The Journal of clinical investigation · 2026Article
- Architects of the Developing Brain: Cytoskeleton-Organizing Molecules in Neurodevelopmental Disorders.Cells · 2026Review
- A Pleiotropic and Functionally DivergentCells · 2025Article
- Disrupted diencephalon development and neuropeptidergic pathways in zebrafish with autism-risk mutations.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The p.R66W Variant inCells · 2024Article
- Clinical and Molecular Cytogenetic Characterization of 2 Sibling Cases with 17q25 Duplication due to Unbalanced Translocation.Molecular syndromology · 2024Article
- An unusual presentation of de novo RAC3 variation in prenatal diagnosis.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Article
- Article
- Pulsatilla saponin D regulates ras-related C3 botulinum toxin substrate 3 (RAC3) to overcome resistance to paclitaxel in lung adenocarcinoma cells.BMC cancer · 2024Article
- Dispensable role of Rac1 and Rac3 after cochlear hair cell specification.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Clinical profiling of MRD48 and functional characterization of two novel pathogenic RAC1 variants.European journal of human genetics : EJHG · 2023Review
- A missense variant at the RAC1-PAK1 binding site of RAC1 inactivates downstream signaling in VACTERL association.Scientific reports · 2023Article
- Activating RAC1 variants in the switch II region cause a developmental syndrome and alter neuronal morphology.Brain : a journal of neurology · 2022Article
- Variant-specific changes in RAC3 function disrupt corticogenesis in neurodevelopmental phenotypes.Brain : a journal of neurology · 2022Article
- Lessons learnt from prenatal exome sequencing.Prenatal diagnosis · 2022Article
- Article
- Novel pathogenic variants and quantitative phenotypic analyses of Robinow syndrome: WNT signaling perturbation and phenotypic variability.HGG advances · 2022Article
- Editorial: Neuronal cytoskeleton and GTPases in health and diseases.Frontiers in cell and developmental biology · 2022Article
- Review
- Novel pathogenic genomic variants leading to autosomal dominant and recessive Robinow syndrome.American journal of medical genetics. Part A · 2021Article
Corrections and comments
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Authors and funding
21 authors at 11 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeRAC3 is an underexamined member of the Rho GTPase gene family that is expressed in the developing brain and linked to key cellular functions. De novo missense variants in the homolog RAC1 were recently associated with developmental disorders. In the RAC subfamily, transforming missense changes at certain shared residues have been observed in human cancers and previously characterized in experimental studies. The purpose of this study was to determine whether constitutional dysregulation of RAC3 is associated with human disease.
methodsWe discovered a RAC3 variant in the index case using genome sequencing, and searched for additional variants using international data-sharing initiatives. Functional effects of the variants were assessed using a multifaceted approach generalizable to most clinical laboratory settings.
resultsWe rapidly identified five individuals with de novo monoallelic missense variants in RAC3, including one recurrent change. Every participant had severe intellectual disability and brain malformations. In silico protein modeling, and prior in vivo and in situ experiments, supported a transforming effect for each of the three different RAC3 variants. All variants were observed in databases of somatic variation in cancer.
conclusionsMissense variants in RAC3 cause a novel brain disorder, likely through a mechanism of constitutive protein activation.
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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.