ArticleThe Journal of clinical investigation2023
CERT1 mutations perturb human development by disrupting sphingolipid homeostasis.
Erratum issuedOpen access · goldAbstract read
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Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers, 1 of them a synthesis that pooled it.
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20citing papers in PubMed, 1 pooled it
6.2field-weighted citation impact, top 3% of its field
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- GPBP or CERT: The Roles in Autoimmunity, Cancer or Neurodegenerative Disease-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Congenital Disorders of Glycosphingolipid Biosynthesis: Ultrarare Severe Syndromes or Relatively Frequent Mild Neurocognitive Illnesses?Biomedicines · 2026Article
- 1-deoxysphingolipids dysregulate membrane properties and cargo trafficking in the early secretory pathway.Cell chemical biology · 2026Article
- The physiological and pathological effects of sphingolipid metabolism and signaling in the central nervous system.Brain pathology (Zurich, Switzerland) · 2026Review
- Fundamental Neurochemistry Review: Sphingolipids and Ceramides in Brain Development.Journal of neurochemistry · 2025Review
- Emerging roles of lipid transfer protein dimerization.Journal of cell science · 2025Review
- The bioactive sphingolipid playbook. A primer for the uninitiated as well as sphingolipidologists.Journal of lipid research · 2025Review
- Beyond Static Tethering at Membrane Contact Sites: Structural Dynamics and Functional Implications of VAP Proteins.Molecules (Basel, Switzerland) · 2025Review
- Article
- Genetic variants and phenotypic data curated for the CAGI6 intellectual disability panel challenge.Human genetics · 2025Article
- iSODA: A Comprehensive Tool for Integrative Omics Data Analysis in Single- and Multi-Omics Experiments.Analytical chemistry · 2025Article
- An update on autophagy disorders.Journal of inherited metabolic disease · 2025Review
- Human genetic defects of sphingolipid synthesis.Journal of inherited metabolic disease · 2025Review
- Live-Cell Identification of Inhibitors of the Lipid Transfer Protein CERT Using Nanoluciferase Bioluminescence Resonance Energy Transfer (NanoBRET).Angewandte Chemie (International ed. in English) · 2024Article
- Regulation of cellular and systemic sphingolipid homeostasis.Nature reviews. Molecular cell biology · 2024Review
- Article
- The conformational plasticity of structurally unrelated lipid transport proteins correlates with their mode of action.PLoS biology · 2024Article
- Fine-tuned protein-lipid interactions in biological membranes: exploration and implications of the ORMDL-ceramide negative feedback loop in the endoplasmic reticulum.Frontiers in cell and developmental biology · 2024Article
- Choroid plexus and perivascular space abnormalities in CerTra syndrome: neuroimaging and histological findings.Frontiers in neurologyArticle
- Mechanisms of Nonvesicular Ceramide Transport.Contact (Thousand Oaks (Ventura County, Calif.))Review
Corrections and comments
- Erratum issued
Authors and funding
85 authors at 20 institutions in 18 countries.
Charlotte GehinInstitute of Bioengineering (IBI), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Museer A LoneInstitute of Clinical Chemistry, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Winston LeeDepartment of Genetics and Development and.
Laura CapolupoInstitute of Bioengineering (IBI), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Sylvia HoInstitute of Bioengineering (IBI), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Adekemi M AdeyemiDepartment of Medical Genetics, Cumming School of Medicine, The University of Calgary, Calgary, Alberta, Canada.
Erica H GerkesUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands.
Alexander Pa StegmannDepartment of Clinical Genetics and School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center, Maastricht, Netherlands.
Estrella López-MartínInstitute of Rare Diseases Research (IIER), Instituto de Salud Carlos III, Madrid, Spain.
Eva Bermejo-SánchezInstitute of Rare Diseases Research (IIER), Instituto de Salud Carlos III, Madrid, Spain.
Beatriz Martínez-DelgadoInstitute of Rare Diseases Research (IIER), Instituto de Salud Carlos III, Madrid, Spain.
Christiane ZweierInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Cornelia KrausInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Bernt PoppInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Vincent StrehlowInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Daniel GräfeDepartment of Pediatric Radiology, University Hospital Leipzig, Leipzig, Leipzig, Germany.
Ina KnerrNational Centre for Inherited Metabolic Disorders, Children's Health Ireland (CHI) at Temple Street, Dublin, Ireland.
Eppie R JonesGenuity Science, Cherrywood Business Park, Dublin, Ireland.
Stefano ZamunerInstitute of Physics, School of Basic Sciences, École Polytechnique Féderale de Lausanne (EPFL), Lausanne, Switzerland.
Luciano A AbriataLaboratory for Biomolecular Modeling and Protein Purification and Structure Facility, EPFL and Swiss Institute of Bioinformatics, Lausanne Switzerland.
Vidya KunnathullyInstitute of Biochemistry and Cell Biology, National Research Council, Naples, Italy.
Brandon E MoellerDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, Canada.
Anthony VocatInstitute of Bioengineering (IBI), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Samuel RommelaereGlobal Health Institute, School of Life Sciences and.
Jean-Philippe BocqueteGlobal Health Institute, School of Life Sciences and.
Evelyne RuchtiBrain Mind Institute, School of Life Sciences, EPFL, Lausanne, Switzerland.
Greta LimoniBrain Mind Institute, School of Life Sciences, EPFL, Lausanne, Switzerland.
Marine Van CampenhoudtBrain Mind Institute, School of Life Sciences, EPFL, Lausanne, Switzerland.
Samuel BourgeatBrain Mind Institute, School of Life Sciences, EPFL, Lausanne, Switzerland.
Petra HenkleinBerlin Institute of Health, Institut für Biochemie, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Christian GilissenRadboud University Medical Center, Department of Human Genetics, Nijmegen, Netherlands.
Bregje W van BonRadboud University Medical Center, Department of Human Genetics, Nijmegen, Netherlands.
Rolph PfundtRadboud University Medical Center, Department of Human Genetics, Nijmegen, Netherlands.
Marjolein H WillemsenRadboud University Medical Center, Department of Human Genetics, Nijmegen, Netherlands.
Jolanda H SchievingRadboud University Medical Center, Department of Pediatric Neurology, Amalia Children's Hospital and Donders Institute for Brain, Cognition and Behavior, Nijmegen, Netherlands.
Emanuela LeonardiMolecular Genetics of Neurodevelopment, Department of Woman and Child Health, University of Padova, Padova, Italy.
Fiorenza SoliMedical Genetics Department, APSS Trento, Trento, Italy.
Alessandra MurgiaFondazione Istituto di Ricerca Pediatrica (IRP), Città della Speranza, Padova, Italy.
Hui GuoCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Qiumeng ZhangCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Kun XiaCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Christina R FagerbergDepartment of Neurology, Odense University Hospital, and Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Christoph P BeierDepartment of Neurology, Odense University Hospital, and Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Martin J LarsenDepartment of Neurology, Odense University Hospital, and Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Irene ValenzuelaDepartment of Clinical and Molecular Genetics, University Hospital Vall d'Hebron, Medicine Genetics Group, Valle Hebron Research Institute, Barcelona, Spain.
Paula Fernández-ÁlvarezDepartment of Clinical and Molecular Genetics, University Hospital Vall d'Hebron, Medicine Genetics Group, Valle Hebron Research Institute, Barcelona, Spain.
Shiyi XiongFetal Medicine Unit and Prenatal Diagnosis Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
Robert ŚmigielDepartment of Family and Pediatric Nursing, Medical University, Wroclaw, Poland.
Vanesa López-GonzálezSección de Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, CIBERER-ISCIII, Murcia, Spain.
Lluís ArmengolQuantitative Genomic Medicine Laboratories, S.L., CSO & CEO, Esplugues del Llobregat, Barcelona, Catalunya, Spain.
Manuela MorleoTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Naples, Italy.
Angelo SelicorniDepartment of Pediatrics, ASST Lariana Sant' Anna Hospital, San Fermo Della Battaglia, Como, Italy.
Annalaura TorellaTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Naples, Italy.
Moira BlythNorth of Scotland Regional Genetics Service, Clinical Genetics Centre, Ashgrove House, Foresterhill, Aberdeen, United Kingdom.
Nicola S CooperW Midlands Clinical Genetics Service, Birmingham Women's Hospital, Edgbaston Birmingham, United Kingdom.
Valerie WilsonNorthern Regional Genetics Laboratory, Newcastle upon Tyne, United Kingdom.
Renske OegemaDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Yvan HerengerGenetica AG, Humangenetisches Labor und Beratungsstelle, Zürich, Switzerland.
Aurore GardeCentre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d'Enfants, CHU Dijon, Dijon, France.
Ange-Line BruelUMR1231 GAD, INSERM - Université Bourgogne-Franche Comté, Dijon, France.
Frederic Tran Mau-ThemUMR1231 GAD, INSERM - Université Bourgogne-Franche Comté, Dijon, France.
Alexis Br MaddocksDepartment of Radiology at Columbia University Irving Medical Center, New York, New York, USA.
Jennifer M BainDepartment of Neurology, Columbia University Irving Medical Center, New York Presbyterian Hospital, Columbia University Medical Center, New York, New York, USA.
Musadiq A BhatInstitute of Pharmacology and Toxicology University of Zürich, Zürich, Switzerland.
Gregory CostainDivision of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Peter KannuDepartment of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.
Ashish MarwahaDepartment of Medical Genetics, Cumming School of Medicine, The University of Calgary, Calgary, Alberta, Canada.
Neena L ChampaigneGreenwood Genetic Center and the Medical University of South Carolina, Greenwood, South Carolina, USA.
Michael J FriezGreenwood Genetic Center and the Medical University of South Carolina, Greenwood, South Carolina, USA.
Ellen B RichardsonGreenwood Genetic Center and the Medical University of South Carolina, Greenwood, South Carolina, USA.
Vykuntaraju K GowdaDepartment of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India.
Varunvenkat M SrinivasanDepartment of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India.
Yask GuptaDivision of Nephrology, Department of Medicine, Columbia University, New York, New York, USA.
Tze Y LimDivision of Nephrology, Department of Medicine, Columbia University, New York, New York, USA.
Simone Sanna-CherchiDivision of Nephrology, Department of Medicine, Columbia University, New York, New York, USA.
Bruno LemaitreGlobal Health Institute, School of Life Sciences and.
Toshiyuki YamajiDepartment of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo, Japan.
Kentaro HanadaDepartment of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo, Japan.
John E BurkeDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, Canada.
Ana Marjia JakšićBrain Mind Institute, School of Life Sciences, EPFL, Lausanne, Switzerland.
Brian D McCabeBrain Mind Institute, School of Life Sciences, EPFL, Lausanne, Switzerland.
Paolo De Los RiosInstitute of Bioengineering (IBI), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Thorsten HornemannInstitute of Clinical Chemistry, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Giovanni D'AngeloInstitute of Bioengineering (IBI), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Vincenzo A GennarinoDepartment of Genetics and Development and.
École Polytechnique Fédérale de Lausanne · CHRadboud University Nijmegen · NLColumbia University Irving Medical Center · USCentral South University · CNColumbia University · USHealth & Life (Taiwan) · TWInserm · FRInstituto de Salud Carlos III · ESMedical University of South Carolina · USUniversity of Southern Denmark · DKUniversity of Zurich · CHHebron University · PSIndira Gandhi Institute of Child Health · INNational Institute of Infectious Diseases · JPUniversity of Calgary · CAUniversity of Campania "Luigi Vanvitelli" · ITAzienda Socio Sanitaria Territoriale Lariana · ITBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DEBirmingham Women's Hospital · GBCentro Tecnológico del Agua · ES
Funding
Deciphering the Role of the Pumilio1 in Two Distinct Neurological DiseasesR01NS109858 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Vincenzo Alessandro Gennarino · 2019 to 2026
$4.1MGenomics of mammalian posterior urethral valvesR01DK115574 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SANNA-CHERCHI, SIMONE · 2017 to 2021
$2.9MNIDDK NIH HHS R01 DK115574NINDS NIH HHS R01 NS109858Wellcome Trust
Abstract
Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome.
Indexed as
CeramidesSphingolipidsHomeostasisHumansMutationProtein Serine-Threonine KinasesCeramidesCERT1 protein, humanProtein Serine-Threonine KinasesSphingolipidsCell BiologyGeneticsLipid raftsNeurodevelopment
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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.