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

• Published in: Biochemical and biophysical research communications Vol. 311; no. 4; pp. 987 - 994
• Main Authors: WuQiang, Fan, Yanase, Toshihiko, Wei, Liu, Oba, Koichi, Nomura, Masatoshi, Okabe, Taijiro, Goto, Kiminobu, Nawata, Hajime
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.11.2003
• Subjects: Ad4BP gene; Ad4BP/SF-1; Adrenal Gland Diseases - genetics; Animals; Asian Continental Ancestry Group; Cercopithecus aethiops; cyp11A gene; cyp19 gene; DAX-1; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Fushi Tarazu Transcription Factors; Genetic Predisposition to Disease - genetics; Homeodomain Proteins; Humans; Kidney - metabolism; Male; Mutation; Polymorphism; Polymorphism, Genetic - genetics; Polymorphism, Genetic - physiology; Protein Structure, Tertiary; Receptors, Cytoplasmic and Nuclear; SF-1 gene; Steroidogenic Factor 1; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Activation - physiology; Ad4BP/SF-1; DAX-1; Polymorphism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2003.10.096

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.