{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:00:55Z","timestamp":1791201655734,"version":"4.2.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":277,"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"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Androgen insensitivity syndrome (AIS) is a 46,XY disorder of sex development caused by pathogenic variants in the androgen receptor (\n                    <jats:italic>AR<\/jats:italic>\n                    ) gene. This study is aimed at characterizing the clinical features and investigating the functional consequences of\n                    <jats:italic>AR<\/jats:italic>\n                    variants identified in a Chinese AIS cohort. A systematic literature review was conducted to compare existing functional assays and pathogenic mechanisms. Multiple in silico tools were applied to predict the functional impact of\n                    <jats:italic>AR<\/jats:italic>\n                    variants, followed by in vitro functional analyses of missense variants in MLTC\u20101 cells. Protein expression was evaluated by Western blotting, subcellular localization by immunofluorescence, and transcriptional activity using a pGL4.11\u2010(ARE)\n                    <jats:sub>3<\/jats:sub>\n                    \u2010TATA\u2010luc dual\u2010luciferase reporter assay. Among reported\n                    <jats:italic>AR<\/jats:italic>\n                    missense variants, only 28% (141\/504) had undergone functional evaluation, comprising 274 assays, mainly ligand\u2010binding and transcriptional activity analyses. In the present cohort, 33 patients with AIS harboring\n                    <jats:italic>AR<\/jats:italic>\n                    variants were analyzed, including 15 patients with complete AIS and 18 patients with partial AIS. Seventeen missense variants were further evaluated using in vitro functional assays. Reduced AR protein expression was observed in 82% (14\/17) of variants, impaired nuclear localization in 59% (10\/17), and reduced transcriptional activity in 53% (9\/17), whereas increased transcriptional activity was observed in 12% (2\/17) of variants. Nuclear localization was positively correlated with transcriptional activity, and residual transcriptional activity was positively associated with EMS scores. These findings demonstrate that\n                    <jats:italic>AR<\/jats:italic>\n                    variants cause AIS through heterogeneous molecular mechanisms and that residual AR function contributes to phenotypic variability.\n                  <\/jats:p>","DOI":"10.1155\/humu\/1882678","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:31:08Z","timestamp":1791199868000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Characterization and Genotype\u2010Phenotype Correlation of Androgen Receptor Variants in Patients With Androgen Insensitivity Syndrome"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3960-9589","authenticated-orcid":false,"given":"Di","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Pediatrics The Sixth Affiliated Hospital of Harbin Medical University Harbin Medical University  Harbin China  hrbmu.edu.cn"},{"name":"Department of Endocrinology Genetics Metabolism Beijing Children\u2032s Hospital Capital Medical University National Center for Children\u2032s Health  Beijing China  ccmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6257-3395","authenticated-orcid":false,"given":"Lijun","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Genetics Metabolism Beijing Children\u2032s Hospital Capital Medical University National Center for Children\u2032s Health  Beijing China  ccmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4655-7942","authenticated-orcid":false,"given":"Yueni","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics College of Basic Medical Sciences Harbin Medical University  Harbin China  hrbmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1262-7383","authenticated-orcid":false,"given":"Chunxiu","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Sixth Affiliated Hospital of Harbin Medical University Harbin Medical University  Harbin China  hrbmu.edu.cn"},{"name":"Department of Endocrinology Genetics Metabolism Beijing Children\u2032s Hospital Capital Medical University National Center for Children\u2032s Health  Beijing China  ccmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(53)90359-7"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci66398"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1530\/ec-24-0567"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14388"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.08.006"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.20945\/2359-3997000000031"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ejendo\/lvae082"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1431"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0253-3006.2010.06.008"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.6.12.1491700"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2024.155677"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-023-00927-4"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0126-2"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddad072"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2021.105834"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2006.06.016"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.1677\/jme.1.01885"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1141448"},{"key":"e_1_2_13_20_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst20170335"},{"key":"e_1_2_13_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00640-9"}],"container-title":["Human 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