Fig. 1

Fig. 1 ABCB6 variants identified in Dyschromatosis Universalis Hereditaria (DUH).

a DUH mutations occur in highly conserved regions of ABCB6, as shown in alignments with Pan troglodytes (chimpanzee, 99.5% identity), Mus musculus (mouse, 89.0% identity), and Danio rerio (zebrafish, 63.6% identity). All percent identities are compared to the human ABCB6. b Western blot shows most DUH mutations express similarly to ABCB6 WT (representative data shown). c Band signals from (b) and replicates show statistically significant reduction in expression level of S170G, S322R, and L356P (p = 0.020, < 0.0001, and < 0.0001, respectively, from unpaired two-tailed Welch’s T-test compared to ABCB6 WT). Data reported as mean ± SEM, N = 5 biological replicates. Western blots show DUH mutants bind ATP-agarose (d) and hemin-agarose (e) comparably to ABCB6 WT. f Quantitation of Western blot signals from ATP- and hemin-agarose pulldowns (d, e) and replicates show DUH mutants bind ATP-agarose and hemin-agarose comparably to ABCB6 WT. Percent of WT binding was calculated as described in Supplementary Methods. No signal of L356P could be detected in the ATP-agarose eluted fraction (d), but a faint band could be detected from the hemin-agarose elution fraction (e). No difference compared to ABCB6 WT was found by unpaired two-tailed Welch’s T-test for any of the mutants binding to hemin-agarose. L356P showed a statistically significant decrease in ATP-agarose binding (p = 0.0004). Data are reported as mean ± SEM. ATP agarose N = 3 biological replicates, hemin agarose N = 4 biological replicates. Each biological replicate was repeated from transfection to western blot. Source data are provided in the Source Data file.