{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:04:01Z","timestamp":1793084641230,"version":"4.5.0"},"reference-count":76,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":183,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100007137","name":"Texas Children's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007137","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-178315"],"award-info":[{"award-number":["PJT-178315"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007856","name":"Baylor College of Medicine","doi-asserted-by":"publisher","award":["P50HD103555"],"award-info":[{"award-number":["P50HD103555"]}],"id":[{"id":"10.13039\/100007856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007915","name":"Baylor College of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203308"],"award-info":[{"award-number":["NIHR203308"]}],"id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R24 OD022005"],"award-info":[{"award-number":["R24 OD022005"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R24 OD031447"],"award-info":[{"award-number":["R24 OD031447"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017236","name":"Huffington Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017236","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["U54 NS093793"],"award-info":[{"award-number":["U54 NS093793"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Human Genetics"],"published-print":{"date-parts":[[2023,11]]},"DOI":"10.1016\/j.ajhg.2023.09.009","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T10:29:20Z","timestamp":1697020160000},"page":"1919-1937","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"title":["Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies"],"prefix":"10.1016","volume":"110","author":[{"given":"Zelha","family":"Nil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish R.","family":"Deshwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Barish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanaa","family":"Choufani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polona","family":"Le Quesne Stabej","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Yap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Haldeman-Englert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine","family":"Prescott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Tveten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arve","family":"V\u00f8llo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon","family":"Haynes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia G.","family":"Wheeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Zon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Cytrynbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah","family":"Jobling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira","family":"Blyth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth","family":"Banka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Afenjar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Mignot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Robin-Renaldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Keren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oguz","family":"Kanca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Wegner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Sisco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan","family":"Shinawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Wangler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Weksberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0099-9945","authenticated-orcid":false,"given":"Gregory","family":"Costain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo J.","family":"Bellen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajhg.2023.09.009_bib1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin Modifications and Their Function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2023.09.009_bib2","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nrg3173","article-title":"Histone methylation: A dynamic mark in health, disease and inheritance","volume":"13","author":"Greer","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib3","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/s41594-019-0298-7","article-title":"Histone lysine methyltransferases in biology and disease","volume":"26","author":"Husmann","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.ajhg.2023.09.009_bib4","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.cell.2007.10.039","article-title":"New Nomenclature for Chromatin-Modifying Enzymes","volume":"131","author":"Allis","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2023.09.009_bib5","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ajhg.2017.11.013","article-title":"Histone Lysine Methylases and Demethylases in the Landscape of Human Developmental Disorders","volume":"102","author":"Faundes","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib6","doi-asserted-by":"crossref","DOI":"10.3390\/biom8010011","article-title":"DOT1L and H3K79 methylation in transcription and genomic stability","volume":"8","author":"Wood","year":"2018","journal-title":"Biomolecules"},{"key":"10.1016\/j.ajhg.2023.09.009_bib7","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S0092-8674(02)00759-6","article-title":"Dot1p modulates silencing in yeast by methylation of the nucleosome core","volume":"109","author":"Van Leeuwen","year":"2002","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2023.09.009_bib8","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/genetics\/150.2.613","article-title":"Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae","volume":"150","author":"Singer","year":"1998","journal-title":"Genetics"},{"key":"10.1016\/j.ajhg.2023.09.009_bib9","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S0092-8674(03)00114-4","article-title":"Structure of the catalytic domain of human Dot1L, a non-SET domain nucleosomal histone methyltransferase","volume":"112","author":"Min","year":"2003","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2023.09.009_bib10","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00412-015-0570-5","article-title":"The upstreams and downstreams of H3K79 methylation by DOT1L","volume":"125","author":"Vlaming","year":"2016","journal-title":"Chromosoma"},{"key":"10.1016\/j.ajhg.2023.09.009_bib11","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/nsmb.1432","article-title":"Nonprocessive methylation by Dot1 leads to functional redundancy of histone H3K79 methylation states","volume":"15","author":"Frederiks","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.ajhg.2023.09.009_bib12","doi-asserted-by":"crossref","first-page":"34655","DOI":"10.1074\/jbc.C200433200","article-title":"Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79","volume":"277","author":"Ng","year":"2002","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ajhg.2023.09.009_bib13","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/nature06906","article-title":"Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation","volume":"453","author":"McGinty","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2023.09.009_bib14","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature00970","article-title":"Trans-histone regulatory pathway in chromatin","volume":"418","author":"Briggs","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2023.09.009_bib15","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1016\/j.cell.2019.02.002","article-title":"Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L","volume":"176","author":"Worden","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2023.09.009_bib16","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1002\/stem.86","article-title":"ES cell cycle progression and differentiation require the action of the histone methyltransferase Dot1L","volume":"27","author":"Barry","year":"2009","journal-title":"Stem Cell."},{"key":"10.1016\/j.ajhg.2023.09.009_bib17","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1038\/emboj.2012.50","article-title":"Bat3 facilitates H3K79 dimethylation by DOT1L and promotes DNA damage-induced 53BP1 foci at G1\/G2 cell-cycle phases","volume":"31","author":"Wakeman","year":"2012","journal-title":"EMBO J."},{"key":"10.1016\/j.ajhg.2023.09.009_bib18","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1101\/gad.1001502","article-title":"Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association","volume":"16","author":"Ng","year":"2002","journal-title":"Genes Dev."},{"key":"10.1016\/j.ajhg.2023.09.009_bib19","doi-asserted-by":"crossref","first-page":"5588","DOI":"10.1074\/jbc.M111.328138","article-title":"Deficiency of H3K79 histone methyltransferase Dot1-like protein (DOT1L) inhibits cell proliferation","volume":"287","author":"Kim","year":"2012","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ajhg.2023.09.009_bib20","doi-asserted-by":"crossref","first-page":"726","DOI":"10.4161\/cc.28104","article-title":"The histone methyltransferase Dot1\/DOT1L as a critical regulator of the cell cycle","volume":"13","author":"Kim","year":"2014","journal-title":"Cell Cycle"},{"key":"10.1016\/j.ajhg.2023.09.009_bib21","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/ng.154","article-title":"Combinatorial patterns of histone acetylations and methylations in the human genome","volume":"40","author":"Wang","year":"2008","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib22","doi-asserted-by":"crossref","first-page":"2825","DOI":"10.1128\/MCB.02076-07","article-title":"DOT1L\/KMT4 Recruitment and H3K79 Methylation Are Ubiquitously Coupled with Gene Transcription in Mammalian Cells","volume":"28","author":"Steger","year":"2008","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.ajhg.2023.09.009_bib23","doi-asserted-by":"crossref","first-page":"9185","DOI":"10.1128\/MCB.01529-06","article-title":"Profile of Histone Lysine Methylation across Transcribed Mammalian Chromatin","volume":"26","author":"Vakoc","year":"2006","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.ajhg.2023.09.009_bib24","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1101\/gad.1198204","article-title":"The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote","volume":"18","author":"Sch\u00fcbeler","year":"2004","journal-title":"Genes Dev."},{"key":"10.1016\/j.ajhg.2023.09.009_bib25","doi-asserted-by":"crossref","first-page":"39698","DOI":"10.1074\/jbc.M112.384057","article-title":"Human histone H3K79 methyltransferase DOT1L methyltransferase binds actively transcribing RNA polymerase II to regulate gene expression","volume":"287","author":"Kim","year":"2012","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ajhg.2023.09.009_bib26","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1000190","article-title":"The histone H3K79 methyltransferase Dot1L is essential for mammalian development and heterochromatin structure","volume":"4","author":"Jones","year":"2008","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib27","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1182\/blood.V120.21.849.849","article-title":"Zebrafish Ortholog of Human DOT1L Regulates Primitive and Transient Definitive Hematopoiesis and Controls hoxa9 and meis1 Expression","volume":"120","author":"Morello","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.ajhg.2023.09.009_bib28","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1534\/genetics.104.033191","article-title":"Characterization of the grappa gene, the Drosophila Histone H3 lysine 79 methyltransferase","volume":"169","author":"Shanower","year":"2005","journal-title":"Genetics"},{"key":"10.1016\/j.ajhg.2023.09.009_bib29","doi-asserted-by":"crossref","first-page":"8218","DOI":"10.1073\/pnas.1119899109","article-title":"Genome-wide association and functional studies identify the DOT1L gene to be involved in cartilage thickness and hip osteoarthritis","volume":"109","author":"Casta\u00f1o Betancourt","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2023.09.009_bib30","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1000539","article-title":"The leukemia-associated Mllt10\/Af10-Dot1l are Tcf4\/\u03b2-catenin coactivators essential for intestinal homeostasis","volume":"8","author":"Mahmoudi","year":"2010","journal-title":"PLoS Biol."},{"key":"10.1016\/j.ajhg.2023.09.009_bib31","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1101\/gad.1898410","article-title":"Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom)","volume":"24","author":"Mohan","year":"2010","journal-title":"Genes Dev."},{"key":"10.1016\/j.ajhg.2023.09.009_bib32","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1056\/NEJMoa1714458","article-title":"Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease","volume":"379","author":"Splinter","year":"2018","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ajhg.2023.09.009_bib33","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ajhg.2017.01.006","article-title":"The Undiagnosed Diseases Network: Accelerating Discovery about Health and Disease","volume":"100","author":"Ramoni","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib34","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2020.18109","article-title":"Genome Sequencing as a Diagnostic Test in Children with Unexplained Medical Complexity","volume":"3","author":"Costain","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"10.1016\/j.ajhg.2023.09.009_bib35","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.ajhg.2023.03.006","article-title":"Trio RNA sequencing in a cohort of medically complex children","volume":"110","author":"Deshwar","year":"2023","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib36","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/humu.22844","article-title":"GeneMatcher: A Matching Tool for Connecting Investigators with an Interest in the Same Gene","volume":"36","author":"Sobreira","year":"2015","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.ajhg.2023.09.009_bib37","first-page":"668","article-title":"The impact of GeneMatcher on international data sharing and collaboration","volume":"43","author":"Hamosh","year":"2022","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.ajhg.2023.09.009_bib38","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":"Clayton","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2023.09.009_bib39","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","article-title":"Minfi: A flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays","volume":"30","author":"Aryee","year":"2014","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ajhg.2023.09.009_bib40","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13059-018-1448-7","article-title":"An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray","volume":"19","author":"Salas","year":"2018","journal-title":"Genome Biol."},{"key":"10.1016\/j.ajhg.2023.09.009_bib41","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2023.09.009_bib42","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.51539","article-title":"An efficient CRISPR-based strategy to insert small and large fragments of DNA using short homology arms","volume":"8","author":"Kanca","year":"2019","journal-title":"Elife"},{"key":"10.1016\/j.ajhg.2023.09.009_bib43","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.35574","article-title":"A gene-specific T2A-GAL4 library for Drosophila","volume":"7","author":"Lee","year":"2018","journal-title":"Elife"},{"key":"10.1016\/j.ajhg.2023.09.009_bib44","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1016\/j.ajhg.2021.06.019","article-title":"TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila","volume":"108","author":"Goodman","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib45","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1242\/dev.088757","article-title":"A versatile platform for creating a comprehensive UAS-ORFeome library in Drosophila","volume":"140","author":"Bischof","year":"2013","journal-title":"Development"},{"key":"10.1016\/j.ajhg.2023.09.009_bib46","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1126\/science.1134426","article-title":"P[acman]: A BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster","volume":"314","author":"Venken","year":"2006","journal-title":"Science"},{"key":"10.1016\/j.ajhg.2023.09.009_bib47","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1126\/sciadv.abn3326","article-title":"Neuronal activity induces glucosylceramide that is secreted via exosomes for lysosomal degradation in glia","volume":"8","author":"Wang","year":"2022","journal-title":"Sci. Adv."},{"key":"10.1016\/j.ajhg.2023.09.009_bib48","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.ajhg.2017.04.010","article-title":"MARRVEL: Integration of Human and Model Organism Genetic Resources to Facilitate Functional Annotation of the Human Genome","volume":"100","author":"Wang","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib49","doi-asserted-by":"crossref","DOI":"10.3791\/59542-v","article-title":"Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information","author":"Wang","year":"2019","journal-title":"J.\u00a0Vis. Exp."},{"key":"10.1016\/j.ajhg.2023.09.009_bib50","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ajhg.2017.09.001","article-title":"DOMINO: Using Machine Learning to Predict Genes Associated with Dominant Disorders","volume":"101","author":"Quinodoz","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib51","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nat"},{"key":"10.1016\/j.ajhg.2023.09.009_bib52","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1152\/ajprenal.00105.2010","article-title":"Dot1a contains three nuclear localization signals and regulates the epithelial Na+ channel (ENaC) at multiple levels","volume":"299","author":"Reisenauer","year":"2010","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"10.1016\/j.ajhg.2023.09.009_bib53","doi-asserted-by":"crossref","first-page":"D412","DOI":"10.1093\/nar\/gkaa913","article-title":"Pfam: The protein families database in 2021","volume":"49","author":"Mistry","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2023.09.009_bib54","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1042\/bj20030839","article-title":"Structure and regulation of the mDot1 gene, a mouse histone H3 methyltransferase","volume":"377","author":"Zhang","year":"2004","journal-title":"Biochem. J."},{"key":"10.1016\/j.ajhg.2023.09.009_bib55","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1000249","article-title":"Misguided Transcriptional Elongation Causes Mixed Lineage Leukemia","volume":"7","author":"Mueller","year":"2009","journal-title":"PLoS Biol."},{"key":"10.1016\/j.ajhg.2023.09.009_bib56","doi-asserted-by":"crossref","first-page":"4445","DOI":"10.1182\/blood-2007-05-090514","article-title":"A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification","volume":"110","author":"Mueller","year":"2007","journal-title":"Blood"},{"key":"10.1016\/j.ajhg.2023.09.009_bib57","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.celrep.2015.04.004","article-title":"Degree of Recruitment of DOT1L to MLL-AF9 Defines Level of H3K79 Di- and Tri-methylation on Target Genes and Transformation Potential","volume":"11","author":"Kuntimaddi","year":"2015","journal-title":"Cell Rep."},{"key":"10.1016\/j.ajhg.2023.09.009_bib58","doi-asserted-by":"crossref","first-page":"41195","DOI":"10.1074\/jbc.M111.284190","article-title":"A novel disrupter of telomere silencing 1-like (DOT1L) interaction is required for signal transducer and activator of transcription 1 (STAT1)-activated gene expression","volume":"286","author":"Shah","year":"2011","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ajhg.2023.09.009_bib59","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1186\/1471-2105-12-357","article-title":"An integrative approach to ortholog prediction for disease-focused and other functional studies","volume":"12","author":"Hu","year":"2011","journal-title":"BMC Bioinf."},{"key":"10.1016\/j.ajhg.2023.09.009_bib60","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl Variant Effect Predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol."},{"key":"10.1016\/j.ajhg.2023.09.009_bib61","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/s41586-022-04965-x","article-title":"The sequences of 150,119 genomes in the UK Biobank","volume":"607","author":"Halldorsson","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2023.09.009_bib62","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-021-03205-y","article-title":"Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program","volume":"590","author":"Taliun","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2023.09.009_bib63","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.ajhg.2016.08.016","article-title":"REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants","volume":"99","author":"Ioannidis","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib64","doi-asserted-by":"crossref","first-page":"D986","DOI":"10.1093\/nar\/gkt958","article-title":"The Database of Genomic Variants: A curated collection of structural variation in the human genome","volume":"42","author":"MacDonald","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2023.09.009_bib65","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.ajhg.2021.06.015","article-title":"Anatomy of DNA methylation signatures: Emerging insights and applications","volume":"108","author":"Chater-Diehl","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib66","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nmeth.1331","article-title":"Versatile P[acman] BAC libraries for transgenesis studies in Drosophila melanogaster","volume":"6","author":"Venken","year":"2009","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ajhg.2023.09.009_bib67","doi-asserted-by":"crossref","first-page":"R53","DOI":"10.1016\/j.cub.2003.12.041","volume":"14","author":"Soller","year":"2004","journal-title":"Curr. Biol."},{"key":"10.1016\/j.ajhg.2023.09.009_bib68","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1101\/gad.8.8.981","article-title":"repo encodes a glial-specific homeo domain protein required in the Drosophila nervous system","volume":"8","author":"Xiong","year":"1994","journal-title":"Genes Dev."},{"key":"10.1016\/j.ajhg.2023.09.009_bib69","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1158\/1535-7163.MCT-17-0256","article-title":"Amplification of the mutation-carrying BRCA2 allele promotes RAD51 loading and PARP inhibitor resistance in the absence of reversion mutations","volume":"19","author":"Park","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.ajhg.2023.09.009_bib70","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1093\/nar\/gky953","article-title":"DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex","volume":"47","author":"Franz","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2023.09.009_bib71","doi-asserted-by":"crossref","first-page":"R254","DOI":"10.1093\/hmg\/ddz174","article-title":"Mendelian disorders of the epigenetic machinery: postnatal malleability and therapeutic prospects","volume":"28","author":"Fahrner","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib72","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1093\/hmg\/ddab110","article-title":"Rare deleterious de novo missense variants in Rnf2\/Ring2 are associated with a neurodevelopmental disorder with unique clinical features","volume":"30","author":"Luo","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2023.09.009_bib73","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1016\/S0960-9822(02)00901-6","article-title":"Methylation of H3-Lysine 79 Is Mediated by a New Family of HMTases without a SET Domain","volume":"12","author":"Feng","year":"2002","journal-title":"Curr. Biol."},{"key":"10.1016\/j.ajhg.2023.09.009_bib74","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/brain\/awad011","article-title":"Third-generation computational approaches for genetic variant interpretation","volume":"146","author":"Costain","year":"2023","journal-title":"Brain"},{"key":"10.1016\/j.ajhg.2023.09.009_bib75","doi-asserted-by":"crossref","first-page":"3895","DOI":"10.1038\/s41467-022-31686-6","article-title":"Loss-of-function, gain-of-function and dominant-negative mutations have profoundly different effects on protein structure","volume":"13","author":"Gerasimavicius","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2023.09.009_bib76","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12929-020-0619-5","article-title":"Modulation of human platelet activation and in\u00a0vivo vascular thrombosis by columbianadin: Regulation by integrin \u03b1iIb\u03b23 inside-out but not outside-in signals","volume":"27","author":"Hou","year":"2020","journal-title":"J.\u00a0Biomed. Sci."}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929723003221?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929723003221?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:23:56Z","timestamp":1762079036000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929723003221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11]]},"references-count":76,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["S0002929723003221"],"URL":"https:\/\/doi.org\/10.1016\/j.ajhg.2023.09.009","relation":{},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[2023,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Human Genetics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajhg.2023.09.009","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 American Society of Human Genetics.","name":"copyright","label":"Copyright"}]}}