A novel variant of NR5A1, p.R350W implicates potential interactions with unknown co-factors or ligands.
Front Endocrinol (Lausanne)
; 13: 1033074, 2022.
Article
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| MEDLINE
| ID: mdl-36743925
ABSTRACT
Introduction:
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. Purpose andmethods:
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.Results:
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.Conclusion:
Our data suggest that NR5A1 has unidentified endogenous ligands or co-activators that selectively potentiate the transcriptional function of NR5A1 in vivo.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Trastorno del Desarrollo Sexual 46,XY
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article