{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:18:17Z","timestamp":1792642697577,"version":"4.5.0"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The vacuolar H+-ATPase is a large multi-subunit proton pump, composed of an integral membrane V0 domain, involved in proton translocation, and a peripheral V1 domain, catalysing ATP hydrolysis. This complex is widely distributed on the membrane of various subcellular organelles, such as endosomes and lysosomes, and plays a critical role in cellular processes ranging from autophagy to protein trafficking and endocytosis. Variants in ATP6V0A1, the brain-enriched isoform in the V0 domain, have been recently associated with developmental delay and epilepsy in four individuals. Here, we identified 17 individuals from 14 unrelated families with both with new and previously characterized variants in this gene, representing the largest cohort to date. Five affected subjects with biallelic variants in this gene presented with a phenotype of early-onset progressive myoclonus epilepsy with ataxia, while 12 individuals carried de novo missense variants and showed severe developmental and epileptic encephalopathy. The R740Q mutation, which alone accounts for almost 50% of the mutations identified among our cases, leads to failure of lysosomal hydrolysis by directly impairing acidification of the endolysosomal compartment, causing autophagic dysfunction and severe developmental defect in Caenorhabditis elegans. Altogether, our findings further expand the neurological phenotype associated with variants in this gene and provide a direct link with endolysosomal acidification in the pathophysiology of ATP6V0A1-related conditions.<\/jats:p>","DOI":"10.1093\/braincomms\/fcab245","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T15:33:00Z","timestamp":1634139180000},"source":"Crossref","is-referenced-by-count":35,"title":["Variants in\n                    <i>ATP6V0A1<\/i>\n                    cause progressive myoclonus epilepsy and developmental and epileptic encephalopathy"],"prefix":"10.1093","volume":"3","author":[{"given":"Laura C","family":"Bott","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitra","family":"Forouhan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oxford, Oxford OX1 3QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Lieto","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, Oxford OX1 3QX, UK"},{"name":"Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples 80121, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambre J","family":"Sala","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Ellerington","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oxford, Oxford OX1 3QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janel O","family":"Johnson","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfina A","family":"Speciale","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oxford, Oxford OX1 3QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Criscuolo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples 80121, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Filla","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples 80121, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chitayat","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada"},{"name":"The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebba","family":"Alkhunaizi","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada"},{"name":"The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Shannon","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea H","family":"Nemeth","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Italian Undiagnosed Diseases Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"Taruscio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Salvatore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Polizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Censi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Floridia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Novelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Daina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ferlini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Neri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Roccatello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Baldovino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Menegatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Angelucci","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 Coppito, L'Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wooi Fang","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oxford, Oxford OX1 3QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"Institute for Research, Hospitalization and Health Care (IRCCS) \u201cG. Gaslini\u201d Institute, Genova 16147, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Zara","sequence":"additional","affiliation":[{"name":"Institute for Research, Hospitalization and Health Care (IRCCS) \u201cG. Gaslini\u201d Institute, Genova 16147, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Helbig","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Biomedical and Health Informatics (DBHi), Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Neurology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko","family":"Muona","sequence":"additional","affiliation":[{"name":"Blueprint Genetics, 02150 Espoo, Finland"},{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland"},{"name":"Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, 00290, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Courage","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland"},{"name":"Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, 00290, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4014-3113","authenticated-orcid":false,"given":"Anna-Elina","family":"Lehesjoki","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland"},{"name":"Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, 00290, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4580-841X","authenticated-orcid":false,"given":"Samuel F","family":"Berkovic","sequence":"additional","affiliation":[{"name":"Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"ATPase Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Pinnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dallas","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D","family":"Turnpenny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Eason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Fleming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty","family":"McWalter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kali","family":"Juliette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Benke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilma","family":"Ortiz-Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Mckeown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amisha B","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Osmond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagdeep S","family":"Walia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianru","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Keren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Perrine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Deshwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth H","family":"Fischbeck","sequence":"additional","affiliation":[{"name":"Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Brancati","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 Coppito, L'Aquila, Italy"},{"name":"IRCCS San Raffaele Pisana, 00163 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard I","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J A","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oxford, Oxford OX1 3QX, UK"},{"name":"Oxford Harrington Rare Disease Centre, University of Oxford, Oxford OX1 3QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-1476","authenticated-orcid":false,"given":"Carlo","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oxford, Oxford OX1 3QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"issue":"6","key":"2021121112564518200_fcab245-B1","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.molcel.2018.02.006","article-title":"The 3.5-\u00c5 CryoEM structure of nanodisc-reconstituted yeast vacuolar ATPase Vo proton channel","volume":"69","author":"Roh","year":"2018","journal-title":"Mol Cell"},{"issue":"7627","key":"2021121112564518200_fcab245-B2","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nature19828","article-title":"Atomic model for the membrane-embedded VO motor of a eukaryotic V-ATPase","volume":"539","author":"Mazhab-Jafari","year":"2016","journal-title":"Nature"},{"issue":"7551","key":"2021121112564518200_fcab245-B3","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nature14365","article-title":"Electron cryomicroscopy observation of rotational states in a eukaryotic V-ATPase","volume":"521","author":"Zhao","year":"2015","journal-title":"Nature"},{"issue":"4","key":"2021121112564518200_fcab245-B4","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.tibs.2019.12.007","article-title":"Structure and roles of V-type ATPases","volume":"45","author":"Vasanthakumar","year":"2020","journal-title":"Trends Biochem Sci"},{"issue":"3","key":"2021121112564518200_fcab245-B5","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.cmet.2014.06.014","article-title":"The lysosomal v-ATPase-ragulator complex is a common activator for AMPK and mTORC1, acting as a switch between catabolism and anabolism","volume":"20","author":"Zhang","year":"2014","journal-title":"Cell Metab"},{"issue":"2","key":"2021121112564518200_fcab245-B6","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/ncb1348","article-title":"V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway","volume":"8","author":"Hurtado-Lorenzo","year":"2006","journal-title":"Nat Cell Biol"},{"issue":"4","key":"2021121112564518200_fcab245-B7","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.cell.2005.03.012","article-title":"The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila","volume":"121","author":"Hiesinger","year":"2005","journal-title":"Cell"},{"issue":"2","key":"2021121112564518200_fcab245-B8","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1074\/jbc.M112.409250","article-title":"Inhibition of glycogen synthase kinase-3 ameliorates \u03b2-amyloid pathology and restores lysosomal acidification and mammalian target of rapamycin activity in the Alzheimer disease mouse model: In vivo and in vitro studies","volume":"288","author":"Avrahami","year":"2013","journal-title":"J Biol Chem"},{"issue":"9","key":"2021121112564518200_fcab245-B9","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1016\/j.celrep.2015.07.050","article-title":"Presenilin 1 maintains lysosomal Ca2+ homeostasis via TRPML1 by regulating vATPase-mediated lysosome acidification","volume":"12","author":"Lee","year":"2015","journal-title":"Cell Rep"},{"issue":"12","key":"2021121112564518200_fcab245-B10","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/81834","article-title":"Chronic systemic pesticide exposure reproduces features of Parkinson\u2019s disease","volume":"3","author":"Betarbet","year":"2000","journal-title":"Nat Neurosci"},{"issue":"9","key":"2021121112564518200_fcab245-B11","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nrd.2018.109","article-title":"Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing","volume":"17","author":"Boland","year":"2018","journal-title":"Nat Rev Drug Discov"},{"issue":"37","key":"2021121112564518200_fcab245-B12","doi-asserted-by":"crossref","first-page":"12535","DOI":"10.1523\/JNEUROSCI.1920-10.2010","article-title":"Pathogenic lysosomal depletion in Parkinson\u2019s disease","volume":"30","author":"Dehay","year":"2010","journal-title":"J Neurosci"},{"issue":"1","key":"2021121112564518200_fcab245-B13","doi-asserted-by":"crossref","first-page":"22866","DOI":"10.1038\/srep22866","article-title":"NADPH oxidase promotes Parkinsonian phenotypes by impairing autophagic flux in an mTORC1-independent fashion in a cellular model of Parkinson\u2019s disease","volume":"6","author":"Pal","year":"2016","journal-title":"Sci Rep"},{"issue":"16","key":"2021121112564518200_fcab245-B14","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1093\/hmg\/ddz088","article-title":"LRRK2 interacts with the vacuolar-type H+-ATPase pump a1 subunit to regulate lysosomal function","volume":"28","author":"Wallings","year":"2019","journal-title":"Hum Mol Genet"},{"issue":"8","key":"2021121112564518200_fcab245-B15","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1080\/15548627.2019.1609863","article-title":"Loss of proteins associated with amyotrophic lateral sclerosis affects lysosomal acidification via different routes","volume":"15","author":"\u015eent\u00fcrk","year":"2019","journal-title":"Autophagy"},{"issue":"1","key":"2021121112564518200_fcab245-B16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2019.1665293","article-title":"A novel role of UBQLNs (ubiquilins) in regulating autophagy, MTOR signaling and v-ATPase function","volume":"16","author":"Yang","year":"2020","journal-title":"Autophagy"},{"issue":"12","key":"2021121112564518200_fcab245-B17","doi-asserted-by":"crossref","first-page":"e1002583","DOI":"10.1371\/journal.pbio.1002583","article-title":"Lysosomal re-acidification prevents lysosphingolipid-induced lysosomal impairment and cellular toxicity","volume":"14","author":"Folts","year":"2016","journal-title":"PLoS Biol"},{"issue":"7","key":"2021121112564518200_fcab245-B18","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/nrm1423","article-title":"The cell biology of lysosomal storage disorders","volume":"5","author":"Futerman","year":"2004","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"3","key":"2021121112564518200_fcab245-B19","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/77131","article-title":"Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis","volume":"25","author":"Frattini","year":"2000","journal-title":"Nat Genet"},{"issue":"13","key":"2021121112564518200_fcab245-B20","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1093\/hmg\/9.13.2059","article-title":"Mutations in the a3 subunit of the vacuolar H+-ATPase cause infantile malignant osteopetrosis","volume":"9","author":"Kornak","year":"2000","journal-title":"Hum Mol Genet"},{"issue":"1","key":"2021121112564518200_fcab245-B21","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/ng.2007.45","article-title":"Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2","volume":"40","author":"Kornak","year":"2008","journal-title":"Nat Genet"},{"issue":"8","key":"2021121112564518200_fcab245-B22","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1074\/jbc.M117.818872","article-title":"Molecular mechanisms of cutis laxa- and distal renal tubular acidosis-causing mutations in V-ATPase a subunits, ATP6V0A2 and ATP6V0A4","volume":"293","author":"Esmail","year":"2018","journal-title":"J Biol Chem"},{"issue":"1","key":"2021121112564518200_fcab245-B23","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/5022","article-title":"Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness","volume":"21","author":"Karet","year":"1999","journal-title":"Nat Genet"},{"issue":"1","key":"2021121112564518200_fcab245-B24","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/79208","article-title":"Mutations in ATP6N1B, encoding a new kidney vacuolar proton pump 116-kD subunit, cause recessive distal renal tubular acidosis with preserved hearing","volume":"26","author":"Smith","year":"2000","journal-title":"Nat Genet"},{"issue":"6","key":"2021121112564518200_fcab245-B25","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1093\/brain\/awy092","article-title":"De novo mutations of the ATP6V1A gene cause developmental encephalopathy with epilepsy","volume":"141","author":"Fassio","year":"2018","journal-title":"Brain"},{"issue":"7","key":"2021121112564518200_fcab245-B26","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0248-4900(03)00075-3","article-title":"Neurotransmitter disease: The dark side of the vacuolar-H+ATPase","volume":"95","author":"Morel","year":"2003","journal-title":"Biol Cell"},{"issue":"19","key":"2021121112564518200_fcab245-B27","doi-asserted-by":"crossref","first-page":"3852","DOI":"10.1093\/hmg\/ddr306","article-title":"Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways","volume":"20","author":"Palmieri","year":"2011","journal-title":"Hum Mol Genet"},{"issue":"7","key":"2021121112564518200_fcab245-B28","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/gim.2015.148","article-title":"Clinical application of whole-exome sequencing across clinical indications","volume":"18","author":"Retterer","year":"2016","journal-title":"Genet Med"},{"issue":"5","key":"2021121112564518200_fcab245-B29","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1001\/jamaneurol.2014.4769","article-title":"Mutation in CPT1C associated with pure autosomal dominant spastic paraplegia","volume":"72","author":"Rinaldi","year":"2015","journal-title":"JAMA Neurol"},{"issue":"1","key":"2021121112564518200_fcab245-B30","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s13052-020-00883-8","article-title":"Improving diagnosis for rare diseases: The experience of the Italian undiagnosed rare diseases network","volume":"46","author":"Salvatore","year":"2020","journal-title":"Ital J Pediatr"},{"issue":"7831","key":"2021121112564518200_fcab245-B31","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/s41586-020-2832-5","article-title":"Evidence for 28 genetic disorders discovered by combining healthcare and research data","volume":"586","author":"Kaplanis","year":"2020","journal-title":"Nature"},{"issue":"8","key":"2021121112564518200_fcab245-B32","doi-asserted-by":"crossref","first-page":"e125","DOI":"10.1111\/epi.14506","article-title":"Evidence of linkage to chromosome 5p13.2-q11.1 in a large inbred family with genetic generalized epilepsy","volume":"59","author":"Kinay","year":"2018","journal-title":"Epilepsia"},{"issue":"1","key":"2021121112564518200_fcab245-B33","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/ng.3144","article-title":"A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy","volume":"47","author":"Muona","year":"2015","journal-title":"Nat Genet"},{"issue":"7","key":"2021121112564518200_fcab245-B34","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1093\/brain\/awaa171","article-title":"Epilepsy subtype-specific copy number burden observed in a genome-wide study of 17458 subjects","volume":"143","author":"Niestroj","year":"2020","journal-title":"Brain"},{"issue":"7642","key":"2021121112564518200_fcab245-B35","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nature21062","article-title":"Prevalence and architecture of de novo mutations in developmental disorders","volume":"542","author":"McRae","year":"2017","journal-title":"Nature"},{"issue":"2","key":"2021121112564518200_fcab245-B36","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/ana.25941","article-title":"Progressive myoclonus epilepsy caused by a homozygous splicing variant of SLC7A6OS","volume":"89","author":"Mazzola","year":"2020","journal-title":"Ann Neurol"},{"issue":"WEB SERVER ISS","key":"2021121112564518200_fcab245-B37","doi-asserted-by":"crossref","first-page":"W526","DOI":"10.1093\/nar\/gkh468","article-title":"Protein structure prediction and analysis using the Robetta server","volume":"32","author":"Kim","year":"2004","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"2021121112564518200_fcab245-B38","doi-asserted-by":"crossref","first-page":"3921","DOI":"10.1038\/s41467-020-17762-9","article-title":"Cryo-EM structures of intact V-ATPase from bovine brain","volume":"11","author":"Wang","year":"2020","journal-title":"Nat Commun"},{"key":"2021121112564518200_fcab245-B39","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.matbio.2018.03.004","article-title":"Paradoxical roles of ATF6\u03b1 and ATF6\u03b2 in modulating disease severity caused by mutations in collagen X","volume":"70","author":"Forouhan","year":"2018","journal-title":"Matrix Biol"},{"issue":"1","key":"2021121112564518200_fcab245-B40","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/genetics\/77.1.71","article-title":"The genetics of Caenorhabditis elegans","volume":"77","author":"Brenner","year":"1974","journal-title":"Genetics"},{"issue":"4","key":"2021121112564518200_fcab245-B41","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1534\/genetics.115.184275","article-title":"SapTrap, a toolkit for high-throughput CRISPR\/Cas9 gene modification in Caenorhabditis elegans","volume":"202","author":"Schwartz","year":"2016","journal-title":"Genetics"},{"key":"2021121112564518200_fcab245-B42","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ymeth.2017.03.023","article-title":"Precision genome editing using CRISPR-Cas9 and linear repair templates in C. elegans","volume":"121-122","author":"Paix","year":"2017","journal-title":"Methods"},{"issue":"4","key":"2021121112564518200_fcab245-B43","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S1046-2023(03)00050-1","article-title":"Genome-wide RNAi screening in Caenorhabditis elegans","volume":"30","author":"Kamath","year":"2003","journal-title":"Methods"},{"issue":"9-10","key":"2021121112564518200_fcab245-B44","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1101\/gad.335422.119","article-title":"Embryo integrity regulates maternal proteostasis and stress resilience","volume":"34","author":"Sala","year":"2020","journal-title":"Genes Dev"},{"issue":"8","key":"2021121112564518200_fcab245-B45","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s00415-005-0766-3","article-title":"Autosomal recessive progressive myoclonus epilepsy with ataxia and mental retardation","volume":"252","author":"Coppola","year":"2005","journal-title":"J Neurol"},{"issue":"7616","key":"2021121112564518200_fcab245-B46","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"issue":"7294","key":"2021121112564518200_fcab245-B47","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nature09000","article-title":"Deciphering the splicing code","volume":"465","author":"Barash","year":"2010","journal-title":"Nature"},{"issue":"22","key":"2021121112564518200_fcab245-B48","doi-asserted-by":"crossref","first-page":"12397","DOI":"10.1073\/pnas.221291798","article-title":"Arg-735 of the 100-kDa subunit a of the yeast V-ATPase is essential for proton translocation","volume":"98","author":"Kawasaki-Nishi","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"2021121112564518200_fcab245-B49","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1016\/S0006-3495(03)74736-5","article-title":"Role of backbone hydration and salt-bridge formation in stability of \u03b1-helix in solution","volume":"85","author":"Ghosh","year":"2003","journal-title":"Biophys J"},{"issue":"4","key":"2021121112564518200_fcab245-B50","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.bbamcr.2008.10.016","article-title":"Sorting of lysosomal proteins","volume":"1793","author":"Braulke","year":"2009","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"issue":"3","key":"2021121112564518200_fcab245-B51","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1515\/cclm.1991.29.3.165","article-title":"Determination of the phosphorylation, uncovering of mannose 6-phosphate groups and targeting of lysosomal enzymes","volume":"29","author":"Isidoro","year":"1991","journal-title":"Clin Chem Lab Med"},{"issue":"Pt 6","key":"2021121112564518200_fcab245-B52","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1093\/brain\/awl107","article-title":"Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis","volume":"129","author":"Siintola","year":"2006","journal-title":"Brain"},{"issue":"6","key":"2021121112564518200_fcab245-B53","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1086\/504159","article-title":"Cathepsin D deficiency is associated with a human neurodegenerative disorder","volume":"78","author":"Steinfeld","year":"2006","journal-title":"Am J Hum Genet"},{"key":"2021121112564518200_fcab245-B54","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41421-020-0141-7","article-title":"Lysosome biology in autophagy","volume":"6","author":"Yim","year":"2020","journal-title":"Cell Discov"},{"issue":"10","key":"2021121112564518200_fcab245-B55","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1242\/dev.148007","article-title":"The developmental biology of genetic notch disorders","volume":"144","author":"Ma\u0161ek","year":"2017","journal-title":"Development"},{"issue":"6","key":"2021121112564518200_fcab245-B56","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.cub.2010.01.049","article-title":"Endocytic internalization routes required for delta\/notch signaling","volume":"20","author":"Windler","year":"2010","journal-title":"Curr Biol"},{"issue":"2","key":"2021121112564518200_fcab245-B57","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ceb.2006.02.011","article-title":"Regulation of Notch signalling by endocytosis and endosomal sorting","volume":"18","author":"Le Borgne","year":"2006","journal-title":"Curr Opin Cell Biol"},{"issue":"4","key":"2021121112564518200_fcab245-B58","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.semcdb.2012.01.008","article-title":"Endocytic routes to Notch activation","volume":"23","author":"Baron","year":"2012","journal-title":"Semin Cell Dev Biol"},{"issue":"1","key":"2021121112564518200_fcab245-B59","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1084\/jem.20120993","article-title":"Hes repressors are essential regulators of hematopoietic stem cell development downstream of notch signaling","volume":"210","author":"Guiu","year":"2013","journal-title":"J Exp Med"},{"issue":"11","key":"2021121112564518200_fcab245-B60","doi-asserted-by":"crossref","first-page":"8763","DOI":"10.1074\/jbc.C100758200","article-title":"Blocking HES1 expression initiates GABAergic differentiation and induces the expression of p21CIP1\/WAF1 in human neural stem cells","volume":"277","author":"Kabos","year":"2002","journal-title":"J Biol Chem"},{"issue":"7-8","key":"2021121112564518200_fcab245-B61","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.bbadis.2008.04.003","article-title":"Caenorhabditis elegans as a model for lysosomal storage disorders","volume":"1782","author":"de Voer","year":"2008","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"35","key":"2021121112564518200_fcab245-B62","doi-asserted-by":"crossref","first-page":"33079","DOI":"10.1074\/jbc.M101652200","article-title":"Four subunit a isoforms of Caenorhabditis elegans vacuolar H +-ATPase: Cell-specific expression during development","volume":"276","author":"Oka","year":"2001","journal-title":"J Biol Chem"},{"issue":"15","key":"2021121112564518200_fcab245-B63","doi-asserted-by":"crossref","first-page":"11913","DOI":"10.1074\/jbc.M009451200","article-title":"The Caenorhabditis elegans unc-32 gene encodes alternative forms of a vacuolar ATPase a subunit","volume":"276","author":"Pujol","year":"2001","journal-title":"J Biol Chem"},{"issue":"3","key":"2021121112564518200_fcab245-B64","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/ng1195-309","article-title":"Developmental expression pattern screen for genes predicted in the C. elegans genome sequencing project","volume":"11","author":"Lynch","year":"1995","journal-title":"Nat Genet"},{"issue":"6","key":"2021121112564518200_fcab245-B65","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1136\/jmedgenet-2018-105775","article-title":"Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing","volume":"56","author":"Iwama","year":"2019","journal-title":"J Med Genet"},{"issue":"1","key":"2021121112564518200_fcab245-B66","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1038\/s41467-021-22389-5","article-title":"ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H+-ATPases is essential for brain development in humans and mice","volume":"12","author":"Aoto","year":"2021","journal-title":"Nat Commun"},{"issue":"Pt 23","key":"2021121112564518200_fcab245-B67","doi-asserted-by":"crossref","first-page":"4751","DOI":"10.1242\/jcs.00791","article-title":"Specific sorting of the a1 isoform of the V-H+ATPase a subunit to nerve terminals where it associates with both synaptic vesicles and the presynaptic plasma membrane","volume":"116","author":"Morel","year":"2003","journal-title":"J Cell Sci"},{"issue":"10","key":"2021121112564518200_fcab245-B68","doi-asserted-by":"crossref","first-page":"6824","DOI":"10.1074\/jbc.275.10.6824","article-title":"Molecular cloning and expression of three isoforms of the 100-kDa a subunit of the mouse vacuolar proton-translocating ATPase","volume":"275","author":"Nishi","year":"2000","journal-title":"J Biol Chem"},{"issue":"9","key":"2021121112564518200_fcab245-B69","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1111\/j.1600-0854.2010.01090.x","article-title":"\u03b3-secretase-dependent cleavage initiates notch signaling from the plasma membrane","volume":"11","author":"Sorensen","year":"2010","journal-title":"Traffic"},{"issue":"5","key":"2021121112564518200_fcab245-B70","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1089\/scd.2010.0484","article-title":"The H+ vacuolar ATPase maintains neural stem cells in the developing mouse cortex","volume":"20","author":"Lange","year":"2011","journal-title":"Stem Cells Dev"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcab245\/40722392\/fcab245.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/3\/4\/fcab245\/41724622\/fcab245.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/3\/4\/fcab245\/41724622\/fcab245.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T07:57:32Z","timestamp":1639209452000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcab245\/6400245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":70,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcab245","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.06.01.21257500","asserted-by":"object"}]},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,10,1]]},"published":{"date-parts":[[2021,10,1]]},"article-number":"fcab245"}}