ArticleHuman mutation2009
A balanced chromosomal translocation disrupting ARHGEF9 is associated with epilepsy, anxiety, aggression, and mental retardation.
Article in Human mutation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 204 citations in OpenAlex.
- Escape From X-Chromosome Inactivation Enables Survival in a Male With an Unbalanced X;19 Translocation.Annals of the New York Academy of Sciences · 2026Article
- Autophagic Pathway on GABARAP Involved in GABANeurochemical research · 2026Review
- Article
- Phosphoinositide- and Collybistin-Dependent Synaptic Clustering of Gephyrin.Journal of neurochemistry · 2025Article
- Milestone Review: Unlocking the Proteomics of Glycine Receptor Complexes.Journal of neurochemistry · 2025Review
- Structure, function, and pathology of Neurexin-3.Genes & diseases · 2023Review
- Deciphering the conformational dynamics of gephyrin-mediated collybistin activation.Biophysical reports · 2022Article
- ARHGEF9 gene variant leads to developmental and epileptic encephalopathy: Genotypic phenotype analysis and treatment exploration.Molecular genetics & genomic medicine · 2022Article
- Recruitment of Plasma Membrane GABA-A Receptors by Submembranous Gephyrin/Collybistin Clusters.Cellular and molecular neurobiology · 2022Article
- Human ARHGEF9 intellectual disability syndrome is phenocopied by a mutation that disrupts collybistin binding to the GABAMolecular psychiatry · 2022Article
- Prenatal diagnosis of 21 fetuses with balanced chromosomal abnormalities (BCAs) using whole-genome sequencing.Frontiers in genetics · 2022Article
- A novelThe Journal of international medical research · 2021Article
- De novo ARHGEF9 missense variants associated with neurodevelopmental disorder in females: expanding the genotypic and phenotypic spectrum of ARHGEF9 disease in females.Neurogenetics · 2021Article
- Analysis of Pathogenic Pseudoexons Reveals Novel Mechanisms Driving Cryptic Splicing.Frontiers in genetics · 2021Article
- Neuroligin-2 dependent conformational activation of collybistin reconstituted in supported hybrid membranes.The Journal of biological chemistry · 2020Article
- Rho GTPases in the Amygdala-A Switch for Fears?Cells · 2020Review
- Clinical and Molecular Characterization of Three Novel ARHGEF9 Mutations in Patients with Developmental Delay and Epilepsy.Journal of molecular neuroscience : MN · 2020Article
- Identification of a Core Amino Acid Motif within the α Subunit of GABACell reports · 2019Article
- Regulators of Rho GTPases in the Nervous System: Molecular Implication in Axon Guidance and Neurological Disorders.International journal of molecular sciences · 2019Review
- Mutation p.R356Q in the Collybistin Phosphoinositide Binding Site Is Associated With Mild Intellectual Disability.Frontiers in molecular neuroscience · 2019Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 5 countries.
Funding
Abstract
Clustering of inhibitory gamma-aminobutyric acid(A) (GABA(A)) and glycine receptors at synapses is thought to involve key interactions between the receptors, a "scaffolding" protein known as gephyrin and the RhoGEF collybistin. We report the identification of a balanced chromosomal translocation in a female patient presenting with a disturbed sleep-wake cycle, late-onset epileptic seizures, increased anxiety, aggressive behavior, and mental retardation, but not hyperekplexia. Fine mapping of the breakpoint indicates disruption of the collybistin gene (ARHGEF9) on chromosome Xq11, while the other breakpoint lies in a region of 18q11 that lacks any known or predicted genes. We show that defective collybistin transcripts are synthesized and exons 7-10 are replaced by cryptic exons from chromosomes X and 18. These mRNAs no longer encode the pleckstrin homology (PH) domain of collybistin, which we now show binds phosphatidylinositol-3-phosphate (PI3P/PtdIns-3-P), a phosphoinositide with an emerging role in membrane trafficking and signal transduction, rather than phosphatidylinositol 3,4,5-trisphosphate (PIP3/PtdIns-3,4,5-P) as previously suggested in the "membrane activation model" of gephyrin clustering. Consistent with this finding, expression of truncated collybistin proteins in cultured neurons interferes with synaptic localization of endogenous gephyrin and GABA(A) receptors. These results suggest that collybistin has a key role in membrane trafficking of gephyrin and selected GABA(A) receptor subtypes involved in epilepsy, anxiety, aggression, insomnia, and learning and memory.
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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.