{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:20:27Z","timestamp":1792264827517,"version":"4.4.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":244,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010814","name":"Anhui Provincial Department of Education","doi-asserted-by":"publisher","award":["2025AHGXZK31479"],"award-info":[{"award-number":["2025AHGXZK31479"]}],"id":[{"id":"10.13039\/501100010814","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Moving from an association signal to a clinically credible biomarker requires several links that are often conflated: verified variant identity, aligned allelic effects, reproducible gene\u2010level association, relevant cellular expression, and a plausible functional consequence. We developed a source\u2010aware multiomics framework to assess MPHOSPH6 in lung adenocarcinoma (LUAD) while keeping those evidence classes separate. Six prespecified rsIDs were recovered from the harmonized TRICL LUAD dataset, of which five reached\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 5 \u00d7 10 \u2212 8. Only rs112333466 and rs76474922 were available with alignable alleles in FinnGen R10, and both showed concordant directions. Fixed\u2010effect estimates were OR = 1.592 for rs112333466\u2010T (95% CI, 1.401\u20131.809;\n                    <jats:italic>p<\/jats:italic>\n                    = 9.91 \u00d7 10 \u2212 13) and OR = 0.819 for rs76474922\u2010C (95% CI, 0.773\u20130.867;\n                    <jats:italic>p<\/jats:italic>\n                    = 1.03 \u00d7 10 \u2212 11). In a prespecified two\u2010variant GTEx v8 lung model, genetically predicted MPHOSPH6 expression was positively associated with LUAD in TRICL (\n                    <jats:italic>Z<\/jats:italic>\n                    = 3.341,\n                    <jats:italic>p<\/jats:italic>\n                    = 8.35 \u00d7 10 \u2212 4) and FinnGen (\n                    <jats:italic>Z<\/jats:italic>\n                    = 2.697,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.0070). This gene\u2010level result did not establish colocalization or connect MPHOSPH6 to the six susceptibility rsIDs. Patient\u2010level analysis of 89,241 immune cells from six paired tumor and normal\u2010adjacent lung samples found no significant difference in MPHOSPH6 pseudobulk abundance (exact paired Wilcoxon\n                    <jats:italic>p<\/jats:italic>\n                    = 0.3125). None of 688 lung\u2010lineage pharmacogenomic tests remained significant after false\u2010discovery\u2010rate correction. Ten recorded MPHOSPH6 missense alleles, including five ClinVar variants of uncertain significance, were curated; structural analysis identified I58 at an experimental RNA\u2010exosome interface and defined a focused perturbation series. MPHOSPH6 is therefore supported as a human\u2013variation\u2010informed candidate for functional evaluation, not as a validated LUAD biomarker, pathogenic gene, drug\u2010response predictor, or therapeutic target.\n                  <\/jats:p>","DOI":"10.1155\/humu\/1879922","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:50:26Z","timestamp":1788360626000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Human Variation\u2010Informed Prioritization of MPHOSPH6 in Lung Adenocarcinoma: A Source\u2010Aware Multiomics Evidence Framework"],"prefix":"10.1155","volume":"2026","author":[{"given":"Chongwen","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5842-1148","authenticated-orcid":false,"given":"Jing","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyun","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9356-7588","authenticated-orcid":false,"given":"Shangke","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13385"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3892"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05473-8"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz1776"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03621-1"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3367"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2056-8"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.06.017"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad965"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz947"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.1.308"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade2574"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1061"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.041"},{"key":"e_1_2_13_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz740"},{"key":"e_1_2_13_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0013-2"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/1879922","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/humu\/1879922","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/1879922","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:50:27Z","timestamp":1788360627000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/humu\/1879922"}},"subtitle":[],"editor":[{"given":"Shaoqiu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/humu\/1879922"],"URL":"https:\/\/doi.org\/10.1155\/humu\/1879922","archive":["Portico"],"relation":{},"ISSN":["1059-7794","1098-1004"],"issn-type":[{"value":"1059-7794","type":"print"},{"value":"1098-1004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-03-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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