Functional characterization of a new human Ad4BP/SF-1 variation, G146A

Fan WuQiang, Toshihiko Yanase, Liu Wei, Koichi Oba, Masatoshi Nomura, Taijiro Okabe, Kiminobu Goto, Hajime Nawata

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Ad4BP/SF-1 plays key roles at all levels of the hypothalamic-pituitary- steroidogenic organ axis and its functional disruption causes endocrine disorders of these organs. However, only three human subjects with Ad4BP/SF-1 mutations have been reported to date, suggesting limited clinical significance as a cause of inborn adrenal or sexual abnormalities. We report the first functional characterization of a new variation found in the hinge region of human Ad4BP/SF-1, G146A. Resulting from a single nucleotide shift (GGG→GCG), G146A bears slightly diminished transactivation activity evidenced by both adrenal specific cyp11A promoter and ovary specific cyp19 promoter II. The variation does not affect protein expression or stability, exhibiting no dominant negative effect. G146A has a normal interaction pattern with standard co-regulators and subnuclear distribution pattern, and can be considered as a nonsynonymous single nucleotide polymorphism, since it occurs in normals and patients with adrenal diseases. In normal Japanese the allele C frequency is 8%, while in a preliminary population of patients with adrenal diseases it is elevated to 30%; suggesting the G146A variation might be of clinical importance.

Original languageEnglish
Pages (from-to)987-994
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume311
Issue number4
DOIs
Publication statusPublished - Nov 28 2003

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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