Figure 1 | Scientific Reports

Figure 1

From: Compensated pathogenic variants in coagulation factors VIII and IX present complex mapping between molecular impact and hemophilia severity

Figure 1

Compensated pathogenic deviations (CPDs): definition and distribution relative to disease severity. (A) Illustration of the concept of CPDs: a mutation that is pathogenic in humans but neutral in other species. The mutation shown in the figure, L69V, affects human FVIII and leads to hemophilia A65. The ___location of this mutation in the multiple sequence alignment of the FVIII family (in the red box) shows that valine appears to be native in other species, such as chimpanzees, mice, and rats. (B) Spatial neighborhood (dark blue residues) of the CPDs (native and mutant residues indicated by light blue and magenta sticks, respectively), where compensatory mutations are more likely to happen7. (C) Distribution of mild (blue) and severe (red) cases associated with CPDs and noCPDs variants for FVIII and FIX. (D) Distribution of mild and severe CPDs in genes for which disease severity annotations are available.

Back to article page