The Spectra of Disease-Causing Mutations in the Ferroportin 1 (SLC40A1) Encoding Gene and Related Iron Overload Phenotypes (Hemochromatosis Type 4 and Ferroportin Disease)

Figure 1

Distribution of the 65 selected variants along the SLC40A1 gene and the secondary structure of the SLC40A1 protein. (a) The SLC40A1 sequence is represented as a horizontal bar, and each of the segments corresponds to individual exons (coding parts in blue and 5- and 3-untranslated regions in grey), in proportional size and numbered. Introns are represented as a short nonproportional line linking exons. Banners above or below the coding sequence indicate the positions of all variations included in Table 1. Variations that have been studied in vitro are presented in green (loss-of-function), red (gain-of-function), or blue (no functional impact). Missense variations with no functional evidence of deleteriousness or neutrality are presented in grey (for 10 substitutions that occur at the same 8 positions than other variations described as LoF or GoF) or orange (for 8 substitutions that occur at 8 positions where no well-recognized pathogenic variant has been seen to date). (b) The 48 amino acid positions known to be mutated in patients with various iron overload phenotypes reported on the secondary structure topology of the human SLC40A1; amino acids for which variations are associated with a functional defect are colored in green (LoF) or red (GoF), whereas those for which no substitution has been characterized functionally are colored in orange. The human FPN1 protein (UniProtKB: Q9NP59) is made of 571 amino acids.

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