{"id":154508,"date":"2025-08-18T01:31:11","date_gmt":"2025-08-18T01:31:11","guid":{"rendered":"https:\/\/www.europesays.com\/us\/154508\/"},"modified":"2025-08-18T01:31:11","modified_gmt":"2025-08-18T01:31:11","slug":"pathogenic-znf319-variant-disrupts-nuclear-localization-and-transcriptional-regulation-to-cause-a-novel-form-of-autosomal-recessive-leukodystrophy","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/us\/154508\/","title":{"rendered":"Pathogenic ZNF319 variant disrupts nuclear localization and transcriptional regulation to cause a novel form of autosomal recessive leukodystrophy"},"content":{"rendered":"<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"1.\">\n<p class=\"c-article-references__text\" id=\"ref-CR1\">van der Knaap MS, Bugiani M. Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms. Acta Neuropathol. 2017;134:351\u201382.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=28638987\" aria-label=\"PubMed reference 1\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed central reference\" data-track-action=\"pubmed central reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5563342\" aria-label=\"PubMed Central reference 1\" target=\"_blank\">PubMed Central<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 1\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=Leukodystrophies%3A%20a%20proposed%20classification%20system%20based%20on%20pathological%20changes%20and%20pathogenetic%20mechanisms&amp;journal=Acta%20Neuropathol&amp;volume=134&amp;pages=351-82&amp;publication_year=2017&amp;author=Knaap%2CMS&amp;author=Bugiani%2CM\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"2.\">\n<p class=\"c-article-references__text\" id=\"ref-CR2\">Vanderver A, Prust M, Tonduti D, Mochel F, Hussey HM, Helman G, et al. Case definition and classification of leukodystrophies and leukoencephalopathies. Mol Genet Metab. 2016;119:164\u201373.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 2\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=Case%20definition%20and%20classification%20of%20leukodystrophies%20and%20leukoencephalopathies&amp;journal=Mol%20Genet%20Metab&amp;volume=119&amp;pages=164-73&amp;publication_year=2016&amp;author=Vanderver%2CA&amp;author=Prust%2CM&amp;author=Tonduti%2CD&amp;author=Mochel%2CF&amp;author=Hussey%2CHM&amp;author=Helman%2CG\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"3.\">\n<p class=\"c-article-references__text\" id=\"ref-CR3\">Matthews JM. Zinc fingers: modular protein domains with multiple functions. Biochim Biophys Acta. 2001;1547:116\u201326.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 3\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=Zinc%20fingers%3A%20modular%20protein%20domains%20with%20multiple%20functions&amp;journal=Biochim%20Biophys%20Acta&amp;volume=1547&amp;pages=116-26&amp;publication_year=2001&amp;author=Matthews%2CJM\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"4.\">\n<p class=\"c-article-references__text\" id=\"ref-CR4\">Mirzaa GM, Chong JX, Piton A, Popp B, Foss K, Guo H, et al. De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder. Genet Med. 2020;22:538\u201346.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=31723249\" aria-label=\"PubMed reference 4\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 4\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=De%20novo%20and%20inherited%20variants%20in%20ZNF292%20underlie%20a%20neurodevelopmental%20disorder%20with%20features%20of%20autism%20spectrum%20disorder&amp;journal=Genet%20Med&amp;volume=22&amp;pages=538-46&amp;publication_year=2020&amp;author=Mirzaa%2CGM&amp;author=Chong%2CJX&amp;author=Piton%2CA&amp;author=Popp%2CB&amp;author=Foss%2CK&amp;author=Guo%2CH\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"5.\">\n<p class=\"c-article-references__text\" id=\"ref-CR5\">Stessman HAF, Willemsen MH, Fenckova M, Penn O, Hoischen A, Xiong B, et al. Disruption of POGZ is associated with intellectual disability and autism spectrum disorders. Am J Hum Genet. 2017;98:541\u201352.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 5\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=Disruption%20of%20POGZ%20is%20associated%20with%20intellectual%20disability%20and%20autism%20spectrum%20disorders&amp;journal=Am%20J%20Hum%20Genet&amp;volume=98&amp;pages=541-52&amp;publication_year=2017&amp;author=Stessman%2CHAF&amp;author=Willemsen%2CMH&amp;author=Fenckova%2CM&amp;author=Penn%2CO&amp;author=Hoischen%2CA&amp;author=Xiong%2CB\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"6.\">\n<p class=\"c-article-references__text\" id=\"ref-CR6\">Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O&#8217;Keeffe S, et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci. 2014;34:11929\u201347.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=25186741\" aria-label=\"PubMed reference 6\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed central reference\" data-track-action=\"pubmed central reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4152602\" aria-label=\"PubMed Central reference 6\" target=\"_blank\">PubMed Central<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 6\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=An%20RNA-sequencing%20transcriptome%20and%20splicing%20database%20of%20glia%2C%20neurons%2C%20and%20vascular%20cells%20of%20the%20cerebral%20cortex&amp;journal=J%20Neurosci&amp;volume=34&amp;pages=11929-47&amp;publication_year=2014&amp;author=Zhang%2CY&amp;author=Chen%2CK&amp;author=Sloan%2CSA&amp;author=Bennett%2CML&amp;author=Scholze%2CAR&amp;author=O%27Keeffe%2CS\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"7.\">\n<p class=\"c-article-references__text\" id=\"ref-CR7\">Cassandri M, Smirnov A, Novelli F, Pitolli C, Agostini M, Malewicz M, et al. Zinc-finger proteins in health and disease. Cell Death Discov. 2017;3:17071.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=29152378\" aria-label=\"PubMed reference 7\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed central reference\" data-track-action=\"pubmed central reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5683310\" aria-label=\"PubMed Central reference 7\" target=\"_blank\">PubMed Central<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 7\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=Zinc-finger%20proteins%20in%20health%20and%20disease&amp;journal=Cell%20Death%20Discov&amp;volume=3&amp;publication_year=2017&amp;author=Cassandri%2CM&amp;author=Smirnov%2CA&amp;author=Novelli%2CF&amp;author=Pitolli%2CC&amp;author=Agostini%2CM&amp;author=Malewicz%2CM\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"8.\">\n<p class=\"c-article-references__text\" id=\"ref-CR8\">Klug A. The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation. Quart Rev Biophys. 2010;43:1\u201321.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 8\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=The%20discovery%20of%20zinc%20fingers%20and%20their%20development%20for%20practical%20applications%20in%20gene%20regulation%20and%20genome%20manipulation&amp;journal=Quart%20Rev%20Biophys&amp;volume=43&amp;pages=1-21&amp;publication_year=2010&amp;author=Klug%2CA\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"9.\">\n<p class=\"c-article-references__text\" id=\"ref-CR9\">Chang YF, Imam JS, Wilkinson MF. The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem. 2007;76:51\u201374.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=17352659\" aria-label=\"PubMed reference 9\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 9\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=The%20nonsense-mediated%20decay%20RNA%20surveillance%20pathway&amp;journal=Annu%20Rev%20Biochem&amp;volume=76&amp;pages=51-74&amp;publication_year=2007&amp;author=Chang%2CYF&amp;author=Imam%2CJS&amp;author=Wilkinson%2CMF\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"10.\">\n<p class=\"c-article-references__text\" id=\"ref-CR10\">Rutkowski DT, Wu J, Back SH, Callaghan MU, Ferris SP, Iqbal J, et al. UPR pathways combine to prevent hepatic steatosis caused by ER stress-mediated suppression of transcriptional master regulators. Dev Cell. 2008;15:829\u201340.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=19081072\" aria-label=\"PubMed reference 10\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed central reference\" data-track-action=\"pubmed central reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2923556\" aria-label=\"PubMed Central reference 10\" target=\"_blank\">PubMed Central<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 10\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=UPR%20pathways%20combine%20to%20prevent%20hepatic%20steatosis%20caused%20by%20ER%20stress-mediated%20suppression%20of%20transcriptional%20master%20regulators&amp;journal=Dev%20Cell&amp;volume=15&amp;pages=829-40&amp;publication_year=2008&amp;author=Rutkowski%2CDT&amp;author=Wu%2CJ&amp;author=Back%2CSH&amp;author=Callaghan%2CMU&amp;author=Ferris%2CSP&amp;author=Iqbal%2CJ\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"11.\">\n<p class=\"c-article-references__text\" id=\"ref-CR11\">Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596:583\u20139.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=34265844\" aria-label=\"PubMed reference 11\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed central reference\" data-track-action=\"pubmed central reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8371605\" aria-label=\"PubMed Central reference 11\" target=\"_blank\">PubMed Central<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 11\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=Highly%20accurate%20protein%20structure%20prediction%20with%20AlphaFold&amp;journal=Nature&amp;volume=596&amp;pages=583-9&amp;publication_year=2021&amp;author=Jumper%2CJ&amp;author=Evans%2CR&amp;author=Pritzel%2CA&amp;author=Green%2CT&amp;author=Figurnov%2CM&amp;author=Ronneberger%2CO\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"12.\">\n<p class=\"c-article-references__text\" id=\"ref-CR12\">DeLano WL. The PyMOL Molecular Graphics System. 2002. <a href=\"https:\/\/pymol.org\" data-track=\"click_references\" data-track-action=\"external reference\" data-track-value=\"external reference\" data-track-label=\"https:\/\/pymol.org\" rel=\"nofollow noopener\" target=\"_blank\">https:\/\/pymol.org<\/a>.<\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"13.\">\n<p class=\"c-article-references__text\" id=\"ref-CR13\">Kozakov D, Hall DR, Xia B, Porter KA, Padhorny D, Yueh C, et al. The ClusPro web server for protein\u2013protein docking. Nat Protoc. 2017;12:255\u201378.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=28079879\" aria-label=\"PubMed reference 13\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed central reference\" data-track-action=\"pubmed central reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5540229\" aria-label=\"PubMed Central reference 13\" target=\"_blank\">PubMed Central<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 13\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=The%20ClusPro%20web%20server%20for%20protein%E2%80%93protein%20docking&amp;journal=Nat%20Protoc&amp;volume=12&amp;pages=255-78&amp;publication_year=2017&amp;author=Kozakov%2CD&amp;author=Hall%2CDR&amp;author=Xia%2CB&amp;author=Porter%2CKA&amp;author=Padhorny%2CD&amp;author=Yueh%2CC\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"14.\">\n<p class=\"c-article-references__text\" id=\"ref-CR14\">Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248\u20139.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=20354512\" aria-label=\"PubMed reference 14\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed central reference\" data-track-action=\"pubmed central reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2855889\" aria-label=\"PubMed Central reference 14\" target=\"_blank\">PubMed Central<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 14\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=A%20method%20and%20server%20for%20predicting%20damaging%20missense%20mutations&amp;journal=Nat%20Methods&amp;volume=7&amp;pages=248-9&amp;publication_year=2010&amp;author=Adzhubei%2CIA&amp;author=Schmidt%2CS&amp;author=Peshkin%2CL&amp;author=Ramensky%2CVE&amp;author=Gerasimova%2CA&amp;author=Bork%2CP\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"15.\">\n<p class=\"c-article-references__text\" id=\"ref-CR15\">Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 2019;47:D886\u2013D894.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=30371827\" aria-label=\"PubMed reference 15\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 15\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=CADD%3A%20predicting%20the%20deleteriousness%20of%20variants%20throughout%20the%20human%20genome&amp;journal=Nucleic%20Acids%20Res&amp;volume=47&amp;pages=D886-D894&amp;publication_year=2019&amp;author=Rentzsch%2CP&amp;author=Witten%2CD&amp;author=Cooper%2CGM&amp;author=Shendure%2CJ&amp;author=Kircher%2CM\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"16.\">\n<p class=\"c-article-references__text\" id=\"ref-CR16\">Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 2011;7:539.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=21988835\" aria-label=\"PubMed reference 16\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed central reference\" data-track-action=\"pubmed central reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3261699\" aria-label=\"PubMed Central reference 16\" target=\"_blank\">PubMed Central<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 16\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=Fast%2C%20scalable%20generation%20of%20high-quality%20protein%20multiple%20sequence%20alignments%20using%20Clustal%20Omega&amp;journal=Mol%20Syst%20Biol&amp;volume=7&amp;publication_year=2011&amp;author=Sievers%2CF&amp;author=Wilm%2CA&amp;author=Dineen%2CD&amp;author=Gibson%2CTJ&amp;author=Karplus%2CK&amp;author=Li%2CW\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"17.\">\n<p class=\"c-article-references__text\" id=\"ref-CR17\">Schymkowitz J, Borg J, Stricher F, Nys R, Rousseau F, Serrano L. The FoldX web server: an online force field. Nucleic Acids Res. 2005;33:W382\u2013W388.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=15980494\" aria-label=\"PubMed reference 17\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed central reference\" data-track-action=\"pubmed central reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1160148\" aria-label=\"PubMed Central reference 17\" target=\"_blank\">PubMed Central<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 17\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=The%20FoldX%20web%20server%3A%20an%20online%20force%20field&amp;journal=Nucleic%20Acids%20Res&amp;volume=33&amp;pages=W382-W388&amp;publication_year=2005&amp;author=Schymkowitz%2CJ&amp;author=Borg%2CJ&amp;author=Stricher%2CF&amp;author=Nys%2CR&amp;author=Rousseau%2CF&amp;author=Serrano%2CL\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"18.\">\n<p class=\"c-article-references__text\" id=\"ref-CR18\">Oughtred R, Stark C, Breitkreutz BJ, Rust J, Boucher L, Chang C, et al. The BioGRID interaction database: 2019 update. Nucleic Acids Res. 2019;47:D529\u2013D541.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=30476227\" aria-label=\"PubMed reference 18\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 18\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=The%20BioGRID%20interaction%20database%3A%202019%20update&amp;journal=Nucleic%20Acids%20Res&amp;volume=47&amp;pages=D529-D541&amp;publication_year=2019&amp;author=Oughtred%2CR&amp;author=Stark%2CC&amp;author=Breitkreutz%2CBJ&amp;author=Rust%2CJ&amp;author=Boucher%2CL&amp;author=Chang%2CC\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"19.\">\n<p class=\"c-article-references__text\" id=\"ref-CR19\">Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, et al. The STRING database in 2021: customizable protein\u2013protein networks, and functional characterization of user-uploaded gene\/measurement sets. Nucleic Acids Res. 2021;49:D605\u2013D612.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=33237311\" aria-label=\"PubMed reference 19\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 19\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=The%20STRING%20database%20in%202021%3A%20customizable%20protein%E2%80%93protein%20networks%2C%20and%20functional%20characterization%20of%20user-uploaded%20gene%2Fmeasurement%20sets&amp;journal=Nucleic%20Acids%20Res&amp;volume=49&amp;pages=D605-D612&amp;publication_year=2021&amp;author=Szklarczyk%2CD&amp;author=Gable%2CAL&amp;author=Nastou%2CKC&amp;author=Lyon%2CD&amp;author=Kirsch%2CR&amp;author=Pyysalo%2CS\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"20.\">\n<p class=\"c-article-references__text\" id=\"ref-CR20\">Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13:2498\u2013504.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=14597658\" aria-label=\"PubMed reference 20\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed central reference\" data-track-action=\"pubmed central reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC403769\" aria-label=\"PubMed Central reference 20\" target=\"_blank\">PubMed Central<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 20\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=Cytoscape%3A%20a%20software%20environment%20for%20integrated%20models%20of%20biomolecular%20interaction%20networks&amp;journal=Genome%20Res&amp;volume=13&amp;pages=2498-504&amp;publication_year=2003&amp;author=Shannon%2CP&amp;author=Markiel%2CA&amp;author=Ozier%2CO&amp;author=Baliga%2CNS&amp;author=Wang%2CJT&amp;author=Ramage%2CD\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"21.\">\n<p class=\"c-article-references__text\" id=\"ref-CR21\">Ge SX, Jung D, Yao R. ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinformatics. 2020;36:2628\u20139.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=31882993\" aria-label=\"PubMed reference 21\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 21\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=ShinyGO%3A%20a%20graphical%20gene-set%20enrichment%20tool%20for%20animals%20and%20plants&amp;journal=Bioinformatics&amp;volume=36&amp;pages=2628-9&amp;publication_year=2020&amp;author=Ge%2CSX&amp;author=Jung%2CD&amp;author=Yao%2CR\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"22.\">\n<p class=\"c-article-references__text\" id=\"ref-CR22\">Uhl\u00e9n M, Fagerberg L, Hallstr\u00f6m BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Tissue-based map of the human proteome. Science. 2015;347:1260419.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=25613900\" aria-label=\"PubMed reference 22\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 22\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=Tissue-based%20map%20of%20the%20human%20proteome&amp;journal=Science&amp;volume=347&amp;publication_year=2015&amp;author=Uhl%C3%A9n%2CM&amp;author=Fagerberg%2CL&amp;author=Hallstr%C3%B6m%2CBM&amp;author=Lindskog%2CC&amp;author=Oksvold%2CP&amp;author=Mardinoglu%2CA\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"23.\">\n<p class=\"c-article-references__text\" id=\"ref-CR23\">Papatheodorou I, Moreno P, Manning J, Fuentes AM, George N, Fexova S, et al. Expression Atlas update: from tissues to single cells. Nucleic Acids Res. 2020;48:D77\u2013D83.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=31665515\" aria-label=\"PubMed reference 23\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 23\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=Expression%20Atlas%20update%3A%20from%20tissues%20to%20single%20cells&amp;journal=Nucleic%20Acids%20Res&amp;volume=48&amp;pages=D77-D83&amp;publication_year=2020&amp;author=Papatheodorou%2CI&amp;author=Moreno%2CP&amp;author=Manning%2CJ&amp;author=Fuentes%2CAM&amp;author=George%2CN&amp;author=Fexova%2CS\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"24.\">\n<p class=\"c-article-references__text\" id=\"ref-CR24\">Abraham MJ, Murtola T, Schulz R, P\u00e1ll S, Smith JC, Hess B, et al. GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX. 2015;1-2:19\u201325.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 24\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=GROMACS%3A%20high%20performance%20molecular%20simulations%20through%20multi-level%20parallelism%20from%20laptops%20to%20supercomputers&amp;journal=SoftwareX&amp;volume=1-2&amp;pages=19-25&amp;publication_year=2015&amp;author=Abraham%2CMJ&amp;author=Murtola%2CT&amp;author=Schulz%2CR&amp;author=P%C3%A1ll%2CS&amp;author=Smith%2CJC&amp;author=Hess%2CB\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\" data-counter=\"25.\">\n<p class=\"c-article-references__text\" id=\"ref-CR25\">Huang J, Rauscher S, Nawrocki G, Ran T, Feig M, de Groot BL, et al. CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nat Methods. 2017;14:71\u201373.<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a data-track=\"click_references\" rel=\"nofollow noopener\" data-track-label=\"link\" data-track-item_id=\"link\" data-track-value=\"pubmed reference\" data-track-action=\"pubmed reference\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=27819658\" aria-label=\"PubMed reference 25\" target=\"_blank\">PubMed<\/a>\u00a0<br \/>\n    <a data-track=\"click_references\" data-track-action=\"google scholar reference\" data-track-value=\"google scholar reference\" data-track-label=\"link\" data-track-item_id=\"link\" rel=\"nofollow noopener\" aria-label=\"Google Scholar reference 25\" href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=CHARMM36m%3A%20an%20improved%20force%20field%20for%20folded%20and%20intrinsically%20disordered%20proteins&amp;journal=Nat%20Methods&amp;volume=14&amp;pages=71-73&amp;publication_year=2017&amp;author=Huang%2CJ&amp;author=Rauscher%2CS&amp;author=Nawrocki%2CG&amp;author=Ran%2CT&amp;author=Feig%2CM&amp;author=Groot%2CBL\" target=\"_blank\"><br \/>\n                    Google Scholar<\/a>\u00a0\n                <\/p>\n<\/li>\n","protected":false},"excerpt":{"rendered":"van der Knaap MS, Bugiani M. Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms.&hellip;\n","protected":false},"author":3,"featured_media":154509,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26],"tags":[90228,23455,18532,21938,14491,815,15577,913,159,67,132,68],"class_list":{"0":"post-154508","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-demyelinating-diseases","9":"tag-disease-genetics","10":"tag-gene-expression","11":"tag-gene-function","12":"tag-gene-therapy","13":"tag-genetics","14":"tag-human-genetics","15":"tag-molecular-medicine","16":"tag-science","17":"tag-united-states","18":"tag-unitedstates","19":"tag-us"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@us\/115047188609916845","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/154508","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/comments?post=154508"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/154508\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media\/154509"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media?parent=154508"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/categories?post=154508"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/tags?post=154508"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}