ArticleNature genetics2006
Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease.
Article in Nature genetics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 233 citations in OpenAlex.
- New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms.The Journal of biological chemistry · 2013Trial
- A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2.The Journal of biological chemistry · 2012Trial
- Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease.The Journal of biological chemistry · 2012Trial
- Transport and inhibition mechanisms of human glycine transporter 2.Nature communications · 2026Article
- The sympathoregulatory region of the mouse rostral brainstem relies on both GABA and glycine to generate inhibitory currents.The Journal of physiology · 2026Article
- Role of the Glycine Transporter GlyT2 in the Neuronal Differentiation of PC12 Cells.International journal of molecular sciences · 2026Article
- Dysmorphic neurons express markers of inhibitory glycinergic signaling in focal cortical dysplasia IIb.Brain pathology (Zurich, Switzerland) · 2026Article
- Spinal glycine receptor alpha 1 coordinates startle behavior through a cell-type specific mechanism.International journal of biological sciences · 2026Article
- Mechanisms of transport and analgesic compounds recognition by glycine transporter 2.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Ubiquitin ligase signalling networks shape presynaptic development, function and disease.The Journal of physiology · 2025Review
- STARDEV Study: Neurodevelopmental Trajectory and Long-Term Outcomes of Patients with Startle Disease/Hyperekplexia.Movement disorders clinical practice · 2025Article
- A New GlyT2 Variant Associated with Hyperekplexia.International journal of molecular sciences · 2025Article
- The emerging role of glycine receptor α2 subunit defects in neurodevelopmental disorders.Frontiers in molecular neuroscience · 2025Review
- Progressive Encephalomyelitis With Rigidity and Myoclonus With Glycine Receptor and GAD65 Antibodies: Case Report and Potential Mechanisms.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- High-Salt Diet Accelerates Neuron Loss and Anxiety inInternational journal of molecular sciences · 2024Article
- Fine mapping and candidate gene analysis of Dravet syndrome modifier loci on mouse chromosomes 7 and 8.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- Article
- Fine Mapping and Candidate Gene Analysis of Dravet Syndrome Modifier Loci on Mouse Chromosomes 7 and 8.bioRxiv : the preprint server for biology · 2024Article
- Role of the Glycine Receptor β Subunit in Synaptic Localization and Pathogenicity in Severe Startle Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Startle Disease: New Molecular Insights into an Old Neurological Disorder.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2023Review
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 13 institutions in 7 countries.
Funding
Abstract
Hyperekplexia is a human neurological disorder characterized by an excessive startle response and is typically caused by missense and nonsense mutations in the gene encoding the inhibitory glycine receptor (GlyR) alpha1 subunit (GLRA1). Genetic heterogeneity has been confirmed in rare sporadic cases, with mutations affecting other postsynaptic glycinergic proteins including the GlyR beta subunit (GLRB), gephyrin (GPHN) and RhoGEF collybistin (ARHGEF9). However, many individuals diagnosed with sporadic hyperekplexia do not carry mutations in these genes. Here we show that missense, nonsense and frameshift mutations in SLC6A5 (ref. 8), encoding the presynaptic glycine transporter 2 (GlyT2), also cause hyperekplexia. Individuals with mutations in SLC6A5 present with hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnea episodes. SLC6A5 mutations result in defective subcellular GlyT2 localization, decreased glycine uptake or both, with selected mutations affecting predicted glycine and Na+ binding sites.
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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.