title: Functional characterization of a new human Ad4BP/SF-1 variation, G146A.
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.
authors: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, 812-8582, Fukuoka, Japan.
authors: Fan
authors: F
authors: WuQiang
authors: Toshihiko
authors: T
authors: Yanase
authors: Liu
authors: L
authors: Wei
authors: Koichi
authors: K
authors: Oba
authors: Masatoshi
authors: M
authors: Nomura
authors: Taijiro
authors: T
authors: Okabe
authors: Kiminobu
authors: K
authors: Goto
authors: Hajime
authors: H
authors: Nawata
mesh_terms: D000307:Adrenal Gland Diseases / Q000235:genetics*; D000818:Animals; D044466:Asian People; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018398:Homeodomain Proteins; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors