Characterization and chromosomal mapping of the human gene for SFT, a stimulator of Fe transport

Hemochromatosis is the most common genetic disorder known in man and result s in progressive tissue deposition of iron leading to cirrhosis of the live r, hepatic carcinoma, congestive heart failure, endocrinopathies, and prema ture death. SFT (stimulator of Fe transport) is a newly discovered transpor t protein that facilitates uptake of iron. Recent studies have demonstrated that although SFT expression is reciprocally regulated in response to cell ular iron levels, it is aberrantly upregulated in the liver of hemochromato sis patients, indicating that enhanced SFT expression contributes to the et iology of this disease. Here we report the molecular cloning and characteri zation of the human gene for SFT, FISH analysis maps the SFT gene to human chromosome 10q21, PCR analysis indicates 1000 nucleotides of intervening in tron sequence near the 3' end of the coding region for SFT. Based on DNA se quence analysis of the additional 5' untranslated region obtained from the genomic clone, SFT lacks known metal-regulated transcriptional or translati onal control elements. These studies provide the basis for future elucidati on of the mechanisms that control SFT expression in order to discover how t his regulation is lost in hemochromatosis. (C) 1998 Academic Press.