{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:05:09Z","timestamp":1790676309161,"version":"4.1.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"31","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872096"],"award-info":[{"award-number":["81872096"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81541152"],"award-info":[{"award-number":["81541152"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,8,3]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Familial nonmedullary thyroid cancer (FNMTC) accounts for up to 15% of all thyroid tumors. Here, we report two germ-line loss-of-function variants in\n                    <jats:italic>WDR77<\/jats:italic>\n                    in two unrelated families with NMTC.\n                    <jats:italic>WDR77<\/jats:italic>\n                    is expressed in diverse human tissues. It forms a complex with the protein arginine methyltransferase PRMT5 and mediates H4R3me2 in frogs and mammals. Functional analyses show that\n                    <jats:italic>WDR77<\/jats:italic>\n                    variants impair formation of the complex of WDR77\u2013PRMT5, resulting in reduced H4R3me2 in patients. Knockdown of\n                    <jats:italic>WDR77<\/jats:italic>\n                    results in increased growth of thyroid cancer cells. Taken together, our findings reveal a predisposing gene of FNMTC and expand the variant profile predisposing to FNMTC. Additionally, this report presents germ-line variants in\n                    <jats:italic>WDR77<\/jats:italic>\n                    associated with human disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2026327118","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T16:11:35Z","timestamp":1627575095000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":20,"title":["Germ-line mutations in\n                    <i>WDR77<\/i>\n                    predispose to familial papillary thyroid cancer"],"prefix":"10.1073","volume":"118","author":[{"given":"Yanyang","family":"Zhao","sequence":"first","affiliation":[{"name":"Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Beijing 100730, China;"},{"name":"Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Beijing 100730, China;"},{"name":"Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China;"},{"name":"Department of General Surgery, Beijing Hospital, National Health Commission, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[{"name":"Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ultrasonography, Beijing Hospital, National Health Commission, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoze","family":"Cheng","sequence":"additional","affiliation":[{"name":"Research &amp; Development, Mingma Technologies Co., Ltd., Shanghai 200131, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shurong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Hospital, National Health Commission, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Hospital, National Health Commission, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghui","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Beijing Hospital, National Health Commission, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Beijing Hospital, National Health Commission, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhuizi","family":"Guan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Beijing 100730, China;"},{"name":"Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China;"},{"name":"Department of General Surgery, Beijing Hospital, National Health Commission, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Beijing 100730, China;"},{"name":"Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Beijing Hospital, National Health Commission, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Beijing Hospital, National Health Commission, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9099-5835","authenticated-orcid":false,"given":"Xiaoquan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Beijing 100730, China;"},{"name":"Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.21147\/j.issn.1000-9604.2019.01.09"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.2719"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0010065"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/86.21.1600"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(200102)9999:9999<::AID-IJC1147>3.0.CO;2-C"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-101412"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.11.8010"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2012.00061"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2009.0216"},{"key":"e_1_3_4_10_2","first-page":"1758","article-title":"Papillary thyroid carcinoma associated with papillary renal neoplasia: Genetic linkage analysis of a distinct heritable tumor syndrome","volume":"85","author":"Malchoff C. D.","year":"2000","unstructured":"C. D. Malchoff ., Papillary thyroid carcinoma associated with papillary renal neoplasia: Genetic linkage analysis of a distinct heritable tumor syndrome. J. Clin. Endocrinol. Metab. 85, 1758\u20131764 (2000).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/321979"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/301610"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-16-0067"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0449"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1502449"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0774"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes10070482"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1209814109"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.636894"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03205-y"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.016"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80216-0"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.43.25507"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks539"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1016"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr407"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22225"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022395"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712262105"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057008"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgx044"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2007.01.017"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-1080"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.12.020"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.003629"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00298-12"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1015"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2026327118","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2026327118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T08:46:08Z","timestamp":1649839568000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2026327118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,29]]},"references-count":40,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2021,8,3]]}},"alternative-id":["10.1073\/pnas.2026327118"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2026327118","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,29]]},"assertion":[{"value":"2021-07-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2026327118"}}