KLF1 gene structure, identification of variants in cases reported in this study, and their location within conserved domains. (top) Schematic representation of KLF1; exons are shown to scale, with the coding sequence in black and untranslated regions in white, and the locations of nucleotide changes identified here. Below this is a diagram representing the KLF1 protein with the previously annotated transactivating domain and the 3 zinc finger domains encoded by exons 2 and 3. The locations of all mutations identified in this study are shown; all changes are novel except for the previously reported R301H substitution (asterisk). (bottom) A position and conservation of amino acid residues found to be changed in the probands reported here (arrows). The entire first and second zinc finger sequences are shown with interspecies conservation, and the extent of each zinc finger domain is shown above each region. The cysteine and histidine residues involved in the coordination of zinc are denoted by the # symbol, and the residues that contact specific bases in DNA are marked with a + symbol.