{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:01:31Z","timestamp":1791378091361,"version":"4.3.2"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DE027091"],"award-info":[{"award-number":["R01DE027091"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020696","name":"Abigail Wexner Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020696","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007520","name":"Nationwide Children\u2019s Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007520","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tumor suppressor candidate 3 is an integral component of the oligosaccharyltransferase complex and is required for the N-glycosylation of proteins. While tumor suppressor candidate 3 has been implicated in cancer and autosomal recessive non-syndromic intellectual disability, some patients also exhibit distinct facial features. However, the role of Tusc3 in craniofacial development is unknown. Here, we report a patient presenting with cleft lip and palate who was found to carry a homozygous variant in the TUSC3 promoter region in addition to a maternally inherited chromosomal duplication. In order to evaluate a potential role for TUSC3 in craniofacial development, we analyzed Tusc3 deletion mouse mutants from the International Mouse Phenotyping Consortium (IMPC). Initial IMPC phenotyping data suggested that a subset of Tusc3 deletion mice could develop cleft palate, micrognathia, and aglossia. We further identified that Tusc3 is expressed in the craniofacial and brain regions during embryonic development. Upon characterizing the Tusc3 deletion line, we observed that most homozygous mutants exhibit preweaning lethality. While craniofacial defects occur at a very low frequency in the deletion mutants, we identified a modest reduction in cortical area. Furthermore, RNA-seq analysis surprisingly revealed that no other genes in the developing brain or face were significantly affected upon loss of Tusc3. These findings suggest that Tusc3 can contribute to congenital malformations in both craniofacial and cortical development.<\/jats:p>","DOI":"10.1093\/g3journal\/jkag224","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:51:50Z","timestamp":1787313110000},"source":"Crossref","is-referenced-by-count":0,"title":["Involvement of\n                    <i>tumor suppressor candidate 3<\/i>\n                    in mouse survival, craniofacial, and cortical development"],"prefix":"10.1093","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0327-5395","authenticated-orcid":false,"given":"Paul P R","family":"Iyyanar","sequence":"first","affiliation":[{"name":"Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute, Nationwide Children's Hospital , Columbus, OH 43205 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Vontell","sequence":"additional","affiliation":[{"name":"Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute, Nationwide Children's Hospital , Columbus, OH 43205 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4287-2857","authenticated-orcid":false,"given":"Ammar","family":"Husami","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Sperry","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K Nicole","family":"Weaver","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-6806","authenticated-orcid":false,"given":"Rolf W","family":"Stottmann","sequence":"additional","affiliation":[{"name":"Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute, Nationwide Children's Hospital , Columbus, OH 43205 ,","place":["United States"]},{"name":"Department of Pediatrics, The Ohio State University College of Medicine , Columbus, OH 43210 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"2026100708164452200_jkag224-B1","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1002\/ajmg.a.37690","article-title":"Homozygous single base deletion in TUSC3 causes intellectual disability with developmental delay in an Omani family","volume":"170","author":"Al-Amri","year":"2016","journal-title":"Am J Med Genet A"},{"key":"2026100708164452200_jkag224-B2","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/s41588-021-00825-y","article-title":"A resource of targeted mutant mouse lines for 5,061 genes","volume":"53","author":"Birling","year":"2021","journal-title":"Nat Genet"},{"key":"2026100708164452200_jkag224-B3","doi-asserted-by":"publisher","DOI":"10.3390\/jdb9030027","article-title":"A novel mutation in Cse1l disrupts brain and eye development with specific effects on Pax6 expression","volume":"9","author":"Blizzard","year":"2021","journal-title":"J Dev Biol"},{"key":"2026100708164452200_jkag224-B4","doi-asserted-by":"publisher","first-page":"9865","DOI":"10.1073\/pnas.1817815116","article-title":"Mutations in MAGT1 lead to a glycosylation disorder with a variable phenotype","volume":"116","author":"Blommaert","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026100708164452200_jkag224-B5","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1006\/geno.1996.0321","article-title":"Physical mapping of chromosome 8p22 markers and their homozygous deletion in a metastatic prostate cancer","volume":"35","author":"Bova","year":"1996","journal-title":"Genomics"},{"key":"2026100708164452200_jkag224-B6","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1016\/j.cell.2022.04.003","article-title":"Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays","volume":"185","author":"Chen","year":"2022","journal-title":"Cell"},{"key":"2026100708164452200_jkag224-B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149028","article-title":"Decreased TUSC3 promotes pancreatic cancer proliferation, invasion and metastasis","volume":"11","author":"Fan","year":"2016","journal-title":"PLoS One"},{"key":"2026100708164452200_jkag224-B8","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.yexcr.2018.08.012","article-title":"TUSC3 accelerates cancer growth and induces epithelial-mesenchymal transition by upregulating claudin-1 in non-small-cell lung cancer cells","volume":"373","author":"Feng","year":"2018","journal-title":"Exp Cell Res"},{"key":"2026100708164452200_jkag224-B9","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1016\/j.ajhg.2008.03.018","article-title":"A defect in the TUSC3 gene is associated with autosomal recessive mental retardation","volume":"82","author":"Garshasbi","year":"2008","journal-title":"Am J Hum Genet"},{"key":"2026100708164452200_jkag224-B10","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1002\/ajmg.a.34077","article-title":"A novel nonsense mutation in TUSC3 is responsible for non-syndromic autosomal recessive mental retardation in a consanguineous Iranian family","volume":"155A","author":"Garshasbi","year":"2011","journal-title":"Am J Med Genet A"},{"key":"2026100708164452200_jkag224-B11","doi-asserted-by":"publisher","first-page":"925","DOI":"10.7754\/Clin.Lab.2015.150101","article-title":"Frequencies of six (five novel) STR markers linked to TUSC3 (MRT7) or NSUN2 (MRT5) genes used for homozygosity mapping of recessive intellectual disability","volume":"61","author":"Ghadami","year":"2015","journal-title":"Clin Lab"},{"key":"2026100708164452200_jkag224-B12","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1016\/j.bbadis.2017.05.005","article-title":"Oncogenic function of TUSC3 in non-small cell lung cancer is associated with Hedgehog signalling pathway","volume":"1863","author":"Gu","year":"2017","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"2026100708164452200_jkag224-B13","doi-asserted-by":"publisher","first-page":"128","DOI":"10.22074\/cellj.2020.6606","article-title":"A homozygous 1.16 megabases microdeletion at 8p22 including the whole TUSC3 in a three years old girl with intellectual disability and speech delay","volume":"22","author":"Gumus","year":"2020","journal-title":"Cell J"},{"key":"2026100708164452200_jkag224-B14","doi-asserted-by":"publisher","DOI":"10.1038\/srep03739","article-title":"TUSC3 loss alters the ER stress response and accelerates prostate cancer growth in vivo","volume":"4","author":"Horak","year":"2014","journal-title":"Sci Rep"},{"key":"2026100708164452200_jkag224-B15","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1002\/mgg3.409","article-title":"Interstitial microdeletion of the 1p34.3p34.2 region","volume":"6","author":"Jacher","year":"2018","journal-title":"Mol Genet Genomic Med"},{"key":"2026100708164452200_jkag224-B16","doi-asserted-by":"publisher","first-page":"12039","DOI":"10.1007\/s13277-016-5072-4","article-title":"TUSC3 suppresses glioblastoma development by inhibiting Akt signaling","volume":"37","author":"Jiang","year":"2016","journal-title":"Tumour Biol"},{"key":"2026100708164452200_jkag224-B17","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/S1097-2765(03)00243-0","article-title":"Oligosaccharyltransferase isoforms that contain different catalytic STT3 subunits have distinct enzymatic properties","volume":"12","author":"Kelleher","year":"2003","journal-title":"Mol Cell"},{"key":"2026100708164452200_jkag224-B18","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/1471-2350-12-56","article-title":"A novel deletion mutation in the TUSC3 gene in a consanguineous Pakistani family with autosomal recessive nonsyndromic intellectual disability","volume":"12","author":"Khan","year":"2011","journal-title":"BMC Med Genet"},{"key":"2026100708164452200_jkag224-B19","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1002\/ijc.29502","article-title":"Tumor suppressor candidate 3 (TUSC3) prevents the epithelial-to-mesenchymal transition and inhibits tumor growth by modulating the endoplasmic reticulum stress response in ovarian cancer cells","volume":"137","author":"Kratochvilova","year":"2015","journal-title":"Int J Cancer"},{"key":"2026100708164452200_jkag224-B20","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1136\/jmg.2008.065821","article-title":"A de novo 1p34.2 microdeletion identifies the synaptic vesicle gene RIMS3 as a novel candidate for autism","volume":"47","author":"Kumar","year":"2010","journal-title":"J Med Genet"},{"key":"2026100708164452200_jkag224-B21","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1002\/ajmg.a.36028","article-title":"Homozygous deletion in TUSC3 causing syndromic intellectual disability: a new patient","volume":"161A","author":"Loddo","year":"2013","journal-title":"Am J Med Genet A"},{"key":"2026100708164452200_jkag224-B22","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1006\/geno.1996.0322","article-title":"Structure and methylation-associated silencing of a gene within a homozygously deleted region of human chromosome band 8p22","volume":"35","author":"MacGrogan","year":"1996","journal-title":"Genomics"},{"key":"2026100708164452200_jkag224-B23","first-page":"479","article-title":"Non-syndromic autosomal recessive mental retardation in Tunisian families: exclusion of GRIK2 and TUSC3 genes","volume":"89","author":"Mhamdi","year":"2011","journal-title":"Tunis Med"},{"key":"2026100708164452200_jkag224-B24","doi-asserted-by":"publisher","DOI":"10.3390\/biom10040624","article-title":"Structural insight into the mechanism of N-linked glycosylation by oligosaccharyltransferase","volume":"10","author":"Mohanty","year":"2020","journal-title":"Biomolecules"},{"key":"2026100708164452200_jkag224-B25","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.str.2014.02.013","article-title":"Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33\/Tusc3 and its role in regulating protein N-glycosylation","volume":"22","author":"Mohorko","year":"2014","journal-title":"Structure"},{"key":"2026100708164452200_jkag224-B26","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1016\/j.ajhg.2008.03.021","article-title":"Oligosaccharyltransferase-subunit mutations in nonsyndromic mental retardation","volume":"82","author":"Molinari","year":"2008","journal-title":"Am J Hum Genet"},{"key":"2026100708164452200_jkag224-B27","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1038\/s41388-019-1032-y","article-title":"UHRF1-KAT7-mediated regulation of TUSC3 expression via histone methylation\/acetylation is critical for the proliferation of colon cancer cells","volume":"39","author":"Taniue","year":"2020","journal-title":"Oncogene"},{"key":"2026100708164452200_jkag224-B28","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/ejhg.2014.202","article-title":"Five children with deletions of 1p34.3 encompassing AGO1 and AGO3","volume":"23","author":"Tokita","year":"2015","journal-title":"Eur J Hum Genet"},{"key":"2026100708164452200_jkag224-B29","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.3892\/ijo.2013.1824","article-title":"Loss of the oligosaccharyl transferase subunit TUSC3 promotes proliferation and migration of ovarian cancer cells","volume":"42","author":"Vanhara","year":"2013","journal-title":"Int J Oncol"},{"key":"2026100708164452200_jkag224-B30","doi-asserted-by":"publisher","first-page":"D1133","DOI":"10.1093\/nar\/gkaf1148","article-title":"International Mouse Phenotyping Consortium Portal: facilitating investigation of gene function and providing insights into human disease","volume":"54","author":"Wilson","year":"2026","journal-title":"Nucleic Acids Res"},{"key":"2026100708164452200_jkag224-B31","doi-asserted-by":"publisher","first-page":"5022","DOI":"10.4238\/2015.May.12.5","article-title":"Association of TUSC3 gene polymorphisms with non-syndromic mental retardation based on nuclear families in the Qinba mountain area of China","volume":"14","author":"Zhang","year":"2015","journal-title":"Genet Mol Res"},{"key":"2026100708164452200_jkag224-B32","doi-asserted-by":"publisher","first-page":"15750","DOI":"10.1073\/pnas.0908332106","article-title":"Mammalian MagT1 and TUSC3 are required for cellular magnesium uptake and vertebrate embryonic development","volume":"106","author":"Zhou","year":"2009","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["G3: Genes, Genomes, Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/g3journal\/advance-article-pdf\/doi\/10.1093\/g3journal\/jkag224\/70752503\/jkag224.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/g3journal\/article-pdf\/16\/10\/jkag224\/70752503\/jkag224.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/g3journal\/article-pdf\/16\/10\/jkag224\/70752503\/jkag224.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:16:56Z","timestamp":1791375416000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/g3journal\/article\/doi\/10.1093\/g3journal\/jkag224\/8767684"}},"subtitle":[],"editor":[{"given":"C","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":32,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,8,21]]},"published-print":{"date-parts":[[2026,10,7]]}},"URL":"https:\/\/doi.org\/10.1093\/g3journal\/jkag224","relation":{},"ISSN":["2160-1836"],"issn-type":[{"value":"2160-1836","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,8,21]]},"article-number":"jkag224"}}