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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,2,26]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    UBE3B is a ubiquitin ligase disrupted in severe neurodevelopmental diseases (NDDs). Mechanistic studies on the function of UBE3B and its substrates have been lacking. Here, we show that deletion of\n                    <jats:italic>Ube3b<\/jats:italic>\n                    in mice causes neuroanatomical, behavioral, and metabolic abnormalities. Moreover, we identify BCKDK as a substrate UBE3B ubiquitinates.\n                    <jats:italic>BCKDK<\/jats:italic>\n                    is mutated in a spectrum of NDDs, and encodes a kinase that regulates several metabolic pathways. We show that\n                    <jats:italic>UBE3B<\/jats:italic>\n                    mutations are associated with metabolic disturbances in plasma from patients. Our findings place two NDD genes,\n                    <jats:italic>UBE3B<\/jats:italic>\n                    and\n                    <jats:italic>BCKDK<\/jats:italic>\n                    , in the same pathway, functionally validate the role of\n                    <jats:italic>UBE3B<\/jats:italic>\n                    in human disease, and identify both a disease mechanism in patients with\n                    <jats:italic>UBE3B<\/jats:italic>\n                    mutations and the downstream substrate that mediates this mechanism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1818751116","type":"journal-article","created":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T20:36:52Z","timestamp":1549917412000},"page":"3662-3667","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["The ubiquitin ligase UBE3B, disrupted in intellectual disability and absent speech, regulates metabolic pathways by targeting BCKDK"],"prefix":"10.1073","volume":"116","author":[{"given":"Solmi","family":"Cheon","sequence":"first","affiliation":[{"name":"Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Kaur","sequence":"additional","affiliation":[{"name":"Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Nijem","sequence":"additional","affiliation":[{"name":"Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Islam Oguz","family":"Tuncay","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Kumar","sequence":"additional","affiliation":[{"name":"Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Dean","sequence":"additional","affiliation":[{"name":"Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Juusola","sequence":"additional","affiliation":[{"name":"GeneDx Inc., Gaithersburg, MD 20877;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Guillen-Sacoto","sequence":"additional","affiliation":[{"name":"GeneDx Inc., Gaithersburg, MD 20877;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Bedoukian","sequence":"additional","affiliation":[{"name":"Roberts Individualized Medical Genetics Center, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne","family":"Ierardi-Curto","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and the Metabolic Disease Program, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and the Metabolic Disease Program, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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