Figure 1.

Schematic of FANCB gene and protein with identified variants. (A) Schematic of FANCB gene with intron-exon organization, complementary DNA coordinates, and the predicted amino acid changes for each identified variant. One IFAR family with a duplication c.-155_952-470dup (p.A319*) has been reported earlier,²⁰ and the duplicated region is shown as a solid line. Two variants from published reports, F118S²¹ and L717*,⁸ are indicated, because their functional status was evaluated in this study. The WGDs extending beyond FANCB are indicated by a dotted line with arrows at the end. For the splice junction variant in intron 7, c.1496+1G>A, the predicted protein change is based on RNA analysis, whereas lack of RNA prevented identifying the consequences for the protein of the intron 8 variant, c.1928-2A>T. (B) Schematic of FANCB protein indicating location of missense variants. The predicted structural motifs, β-propeller, and nuclear localization signal (NLS) are shown. The conservation score plot of FANCB across 99 vertebrate homologs is shown below. For each amino acid that is altered in an individual with FA, the sequence logo derived from 99 FANCB vertebrate homologs is shown for the affected and the adjacent amino acids. The consensus sequence and the human WT FANCB sequence are above and below the logo, respectively. The location of the nonsense variant p.L717* is also shown.