{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:57:00Z","timestamp":1791496620967,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T00:00:00Z","timestamp":1604880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["SCOPES IZ73Z0_152347\/1"],"award-info":[{"award-number":["SCOPES IZ73Z0_152347\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Androgen insensitivity syndrome (AIS), manifesting incomplete virilization in 46,XY individuals, is caused mostly by androgen receptor (AR) gene mutations. Therefore, a search for AR mutations is a routine approach in AIS diagnosis. However, some AIS patients lack AR mutations, which complicates the diagnosis. Here, we describe a patient suffering from partial androgen insensitivity syndrome (PAIS) and lacking AR mutations. The whole exome sequencing of the patient and his family members identified a heterozygous FKBP4 gene mutation, c.956T&gt;C (p.Leu319Pro), inherited from the mother. The gene encodes FKBP prolyl isomerase 4, a positive regulator of the AR signaling pathway. This is the first report describing a FKBP4 gene mutation in association with a human disorder of sexual development (DSD). Importantly, the dysfunction of a homologous gene was previously reported in mice, resulting in a phenotype corresponding to PAIS. Moreover, the Leu319Pro amino acid substitution occurred in a highly conserved position of the FKBP4 region, responsible for interaction with other proteins that are crucial for the AR functional heterocomplex formation and therefore the substitution is predicted to cause the disease. We proposed the FKBP4 gene as a candidate AIS gene and suggest screening that gene for the molecular diagnosis of AIS patients lacking AR gene mutations.<\/jats:p>","DOI":"10.3390\/ijms21218403","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T14:10:41Z","timestamp":1605017441000},"page":"8403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1024-7491","authenticated-orcid":false,"given":"Erkut","family":"Ilaslan","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0860-2340","authenticated-orcid":false,"given":"Renata","family":"Markosyan","sequence":"additional","affiliation":[{"name":"Endocrinology Department, \u201cMuratsan\u201d University Hospital, Endocrinology Clinic, Yerevan State Medical University, 0025 Yerevan, Armenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Sproll","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, University of Fribourg, 1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0599-7543","authenticated-orcid":false,"given":"Malgorzata","family":"Sajek","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, 61-614 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-4191","authenticated-orcid":false,"given":"Marcin P.","family":"Sajek","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0162-2680","authenticated-orcid":false,"given":"Hasmik","family":"Hayrapetyan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Yerevan State Medical University, 0025 Yerevan, Armenia"},{"name":"Center of Medical Genetics and Primary Health Care, 375010 Yerevan, Armenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4767-7567","authenticated-orcid":false,"given":"Tamara","family":"Sarkisian","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Yerevan State Medical University, 0025 Yerevan, Armenia"},{"name":"Center of Medical Genetics and Primary Health Care, 375010 Yerevan, Armenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5444-3964","authenticated-orcid":false,"given":"Ludmila","family":"Livshits","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03143 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5462-0676","authenticated-orcid":false,"given":"Serge","family":"Nef","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, CH-1211 Gen\u00e8ve 4, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2355-0729","authenticated-orcid":false,"given":"Jadwiga","family":"Jaruzelska","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6567-1193","authenticated-orcid":false,"given":"Kamila","family":"Kusz-Zamelczyk","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1016\/S0140-6736(12)60071-3","article-title":"Androgen insensitivity syndrome","volume":"380","author":"Hughes","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.bbagrm.2014.05.020","article-title":"Androgens and mammalian male reproductive tract development","volume":"1849","author":"Murashima","year":"2015","journal-title":"Biochim. 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