{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T07:16:53Z","timestamp":1783495013749,"version":"3.55.0"},"reference-count":31,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-102758 and PJT-156402"],"award-info":[{"award-number":["MOP-102758 and PJT-156402"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Nucleolin (NCL\/C23; OMIM: 164035) is a major nucleolar protein that plays a critical role in multiple processes, including ribosome assembly and maturation, chromatin decondensation, and pre-rRNA transcription. Due to its diverse functions, nucleolin has frequently been implicated in pathological processes, including cancer and viral infection. We recently identified a de novo frameshifting indel mutation of NCL, p.Gly664Glufs*70, through whole-exome sequencing of autism spectrum disorder trios. Through the transfection of constructs encoding either a wild-type human nucleolin or a mutant nucleolin with the same C-terminal sequence predicted for the autism proband, and by using co-localization with the nucleophosmin (NPM; B23) protein, we have shown that the nucleolin mutation leads to mislocalization of the NCL protein from the nucleolus to the nucleoplasm. Moreover, a construct with a nonsense mutation at the same residue, p.Gly664*, shows a very similar effect on the location of the NCL protein, thus confirming the presence of a predicted nucleolar location signal in this region of the NCL protein. Real-time fluorescence recovery experiments show significant changes in the kinetics and mobility of mutant NCL protein in the nucleoplasm of HEK293Tcells. Several other studies also report de novoNCL mutations in ASD or neurodevelopmental disorders. The altered mislocalization and dynamics of mutant NCL (p.G664Glufs*70\/p.G664*) may have relevance to the etiopathlogy of NCL-related ASD and other neurodevelopmental phenotypes.<\/jats:p>","DOI":"10.3390\/genes13010051","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T08:38:46Z","timestamp":1640335126000},"page":"51","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Heterozygous De Novo Truncating Mutation of Nucleolin in an ASD Individual Disrupts Its Nucleolar Localization"],"prefix":"10.3390","volume":"13","author":[{"given":"Taimoor I.","family":"Sheikh","sequence":"first","affiliation":[{"name":"Molecular Neuropsychiatry & Development (MiND) Lab, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Harripaul","sequence":"additional","affiliation":[{"name":"Molecular Neuropsychiatry & Development (MiND) Lab, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"},{"name":"Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Vasli","sequence":"additional","affiliation":[{"name":"Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid","family":"Ghadami","sequence":"additional","affiliation":[{"name":"Department of Educational Sciences, Farhangian University, Tehran 19989-63341, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Santangelo","sequence":"additional","affiliation":[{"name":"Center for Psychiatric Research, Maine Medical Center Research Institute, Portland, ME 04101, USA"},{"name":"Department of Psychiatry, Tufts University School of Medicine, Boston, MA 02110, USA"},{"name":"Department of Psychiatry, Maine Medical Center, Portland, ME 04102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ayub","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Queen\u2019s University, Kingston, ON K7L 7X3, Canada"},{"name":"Department of Academic Psychiatry, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roksana","family":"Sasanfar","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA"},{"name":"Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0692-2519","authenticated-orcid":false,"given":"John B.","family":"Vincent","sequence":"additional","affiliation":[{"name":"Molecular Neuropsychiatry & Development (MiND) Lab, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"},{"name":"Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nature03207","article-title":"Nucleolar proteome dynamics","volume":"433","author":"Andersen","year":"2005","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.bbrc.2005.05.022","article-title":"Nucleolin is regulated both at the level of transcription and translation","volume":"332","author":"Bicknell","year":"2005","journal-title":"Biochem. 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