{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:34:12Z","timestamp":1783488852576,"version":"3.55.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>NR5A1 and NR5A2 belong to an orphan nuclear receptor group, and approximately 60% of their amino acid sequences are conserved. Transcriptional regulation of NR5A receptors depends on interactions with co-factors or unidentified ligands.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose and methods<\/jats:title><jats:p>We employed in vitro and in silico analysis for elucidating the pathophysiology of a novel variant in the ligand-binding domain of NR5A1, p.R350W which was identified from a 46,XY patient with atypical genitalia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the study, [1] reporter assays demonstrated that R350 is essential for NR5A1; [2] 3D model analysis predicted that R350 interacted with endogenous ligands or unknown cofactors rather than stabilizing the structure; [3] R350 is not conserved in NR5A2 but is specifically required for NR5A1; and [4] none of the 22 known missense variants of the ligand binding domain satisfied all the previous conditions [1]-[3], suggesting the unique role of R350 in NR5A1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that NR5A1 has unidentified endogenous ligands or co-activators that selectively potentiate the transcriptional function of NR5A1 <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.1033074","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T05:29:45Z","timestamp":1674192585000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel variant of NR5A1, p.R350W implicates potential interactions with unknown co-factors or 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