{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:20:18Z","timestamp":1787318418309,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["D15D18000410001"],"award-info":[{"award-number":["D15D18000410001"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH111661"],"award-info":[{"award-number":["MH111661"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019565","name":"Research Innovation and Development Trust, University of Malta","doi-asserted-by":"publisher","award":["I20LU08"],"award-info":[{"award-number":["I20LU08"]}],"id":[{"id":"10.13039\/501100019565","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019565","name":"Research Innovation and Development Trust, University of Malta","doi-asserted-by":"publisher","award":["BooKind E20LG42"],"award-info":[{"award-number":["BooKind E20LG42"]}],"id":[{"id":"10.13039\/501100019565","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006013","name":"United Arab Emirates University","doi-asserted-by":"publisher","award":["31M452"],"award-info":[{"award-number":["31M452"]}],"id":[{"id":"10.13039\/501100006013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006013","name":"United Arab Emirates University","doi-asserted-by":"publisher","award":["31M468"],"award-info":[{"award-number":["31M468"]}],"id":[{"id":"10.13039\/501100006013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006013","name":"United Arab Emirates University","doi-asserted-by":"publisher","award":["12M020"],"award-info":[{"award-number":["12M020"]}],"id":[{"id":"10.13039\/501100006013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The TWIK-related spinal cord potassium channel (TRESK) is encoded by KCNK18, and variants in this gene have previously been associated with susceptibility to familial migraine with aura (MIM #613656). A single amino acid substitution in the same protein, p.Trp101Arg, has also been associated with intellectual disability (ID), opening the possibility that variants in this gene might be involved in different disorders. Here, we report the identification of KCNK18 biallelic missense variants (p.Tyr163Asp and p.Ser252Leu) in a family characterized by three siblings affected by mild-to-moderate ID, autism spectrum disorder (ASD) and other neurodevelopment-related features. Functional characterization of the variants alone or in combination showed impaired channel activity. Interestingly, Ser252 is an important regulatory site of TRESK, suggesting that alteration of this residue could lead to additive downstream effects. The functional relevance of these mutations and the observed co-segregation in all the affected members of the family expand the clinical variability associated with altered TRESK function and provide further insight into the relationship between altered function of this ion channel and human disease.<\/jats:p>","DOI":"10.3390\/ijms22116064","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T11:12:13Z","timestamp":1622805133000},"page":"6064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["KCNK18 Biallelic Variants Associated with Intellectual Disability and Neurodevelopmental Disorders Alter TRESK Channel Activity"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7630-8365","authenticated-orcid":false,"given":"Lisa","family":"Pavinato","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"},{"name":"Center for Molecular Medicine Cologne, Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan","family":"Nematian-Ardestani","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, MSD-2080 Msida, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Zonta","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics, \u201cCitt\u00e0 della Salute e della Scienza\u201d University Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9383-6883","authenticated-orcid":false,"given":"Silvia","family":"De Rubeis","sequence":"additional","affiliation":[{"name":"Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Buxbaum","sequence":"additional","affiliation":[{"name":"Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1282-0404","authenticated-orcid":false,"given":"Cecilia","family":"Mancini","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Ges\u00f9, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Bruselles","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Ges\u00f9, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2857-6795","authenticated-orcid":false,"given":"Mauro","family":"Pessia","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, MSD-2080 Msida, Malta"},{"name":"Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 17666, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 4BH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6758-6064","authenticated-orcid":false,"given":"Maria Cristina","family":"D\u2019Adamo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, MSD-2080 Msida, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8318-7231","authenticated-orcid":false,"given":"Alfredo","family":"Brusco","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"},{"name":"Unit of Medical Genetics, \u201cCitt\u00e0 della Salute e della Scienza\u201d University Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/bph.14518","article-title":"Two-pore domain potassium channels: Emerging targets for novel analgesic drugs: IUPHAR Review 26","volume":"176","author":"Gada","year":"2019","journal-title":"Br. 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