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 results in progressive tissue deposition of iron leading to cirrhosis of the liver, hepatic carcinoma, congestive heart failure, endocrinopathies, and premature death. SFT (stimulator of Fe transport) is a newly discovered transport protein that facilitates uptake of iron. Recent studies have demonstrated that although SFT expression is reciprocally regulated in response to cellular iron levels, it is aberrantly upregulated in the liver of hemochromatosis patients, indicating that enhanced SFT expression contributes to the etiology of this disease. Here we report the molecular cloning and characterization of the human gene for SFT. FISH analysis maps the SFT gene to human chromosome 10q21. PCR analysis indicates 1000 nucleotides of intervening intron sequence near the 3' end of the coding region for SFT. Based on DNA sequence analysis of the additional 5' untranslated region obtained from the genomic clone, SFT lacks known metal-regulated transcriptional or translational control elements. These studies provide the basis for future elucidation of the mechanisms that control SFT expression in order to discover how this regulation is lost in hemochromatosis.