Figure 2.

Domain-wide analysis of patient and population variants. (A) The TM1/6, scaffold and EL4 regions harboured mainly variants with low activity, whereas the N-/C-terminal domain contained mostly variants with wild-type (WT) activity. The dotted line represents the cut-off that separates wild-type activity variants (>42.8% of wild-type activity) from low activity variants (<42.8% of wild-type activity). (B) A domain-wide comparison of patient versus population variants shows enrichment of patient variants in TM1/6 and EL4. The N- and C-terminal regions are depleted for patient variants. The dotted line represents a balance between patient and population variants. TM1/6 = transmembrane helix 1/6; TMD-other = transmembrane domain other; EL2/3/4 = extracellular loops 2/3/4; OR = odds ratio.