ArticleHuman molecular genetics2017
Identification of a novel synaptic protein, TMTC3, involved in periventricular nodular heterotopia with intellectual disability and epilepsy.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Gene variants in periventricular nodular heterotopia.Acta epileptologica · 2026Review
- O-Mannose Glycosylations Influence E-Cadherin Functional Interactions.Molecular & cellular proteomics : MCP · 2026Article
- Prognostic value ofHeliyon · 2024Article
- Global View of Domain-Specific O-Linked Mannose Glycosylation in Glycoengineered Cells.Molecular & cellular proteomics : MCP · 2024Article
- Protein O-mannosylation: one sugar, several pathways, many functions.Glycobiology · 2023Review
- Functional unknomics: Systematic screening of conserved genes of unknown function.PLoS biology · 2023Article
- The SHDRA syndrome-associated geneProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3.Open medicine (Warsaw, Poland) · 2023Article
- A Drosophila model of the neurological symptoms in Mpv17-related diseases.Scientific reports · 2022Article
- The clinical and imaging features of FLNA positive and negative periventricular nodular heterotopia.Biomedical journal · 2022Article
- Invertebrate Model Organisms as a Platform to Investigate Rare Human Neurological Diseases.Experimental neurobiology · 2022Review
- Inter-Species Rescue of Mutant Phenotype-The Standard for Genetic Analysis of Human Genetic Disorders inInternational journal of molecular sciences · 2022Review
- Conserved sequence motifs in human TMTC1, TMTC2, TMTC3, and TMTC4, new O-mannosyltransferases from the GT-C/PMT clan, are rationalized as ligand binding sites.Biology direct · 2021Article
- Glycobiology and schizophrenia: a biological hypothesis emerging from genomic research.Molecular psychiatry · 2020Review
- Novel compound variants of theExperimental and therapeutic medicine · 2020Article
- Investigating Developmental and Epileptic Encephalopathy UsingInternational journal of molecular sciences · 2020Review
- The Canadian Rare Diseases Models and Mechanisms (RDMM) Network: Connecting Understudied Genes to Model Organisms.American journal of human genetics · 2020Article
- Endoplasmic reticulum transmembrane protein TMTC3 contributes to O-mannosylation of E-cadherin, cellular adherence, and embryonic gastrulation.Molecular biology of the cell · 2020Article
- Extracellular Control of Radial Glia Proliferation and Scaffolding During Cortical Development and Pathology.Frontiers in cell and developmental biology · 2020Review
- A Report on a Family withCase reports in medicine · 2020Article
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently unexplored in the brain, we gathered support for a neurobiological role for TMTC3 by generating flies with post-mitotic neuron-specific knockdown of the highly conserved Drosophila melanogaster TMTC3 ortholog, CG4050/tmtc3. Neuron-specific knockdown of tmtc3 in flies resulted in increased susceptibility to induced seizures. Importantly, this phenotype was rescued by neuron-specific expression of human TMTC3, suggesting a role for TMTC3 in seizure biology. In addition, we observed co-localization of TMTC3 in the rat brain with vesicular GABA transporter (VGAT), a presynaptic marker for inhibitory synapses. TMTC3 is localized at VGAT positive pre-synaptic terminals and boutons in the rat hypothalamus and piriform cortex, suggesting a role for TMTC3 in the regulation of GABAergic inhibitory synapses. TMTC3 did not co-localize with Vglut2, a presynaptic marker for excitatory neurons. Our data identified TMTC3 as a synaptic protein that is involved in PVNH with ID and epilepsy, in addition to its previously described association with cobblestone lissencephaly.
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