Linking phenotype to genotype for Donor 3. Unlike Donors 1 and 2, Donor 3 displayed almost no calcium response (time courses obtained from PAS experiments in Figure 2) to increasing doses of U46619 (A). Platelets from Donor 3 were unresponsive to 2μM U46619 in a platelet-rich plasma aggregation assay relative to a healthy donor (B). A heterozygote T → G mutation in the TP receptor was found in Donor 3, resulting in the V241G mutation (C). Transient expression of TP-V241G in HEK cells resulted in cells that were unresponsive to U46619 at conditions that activated calcium mobilization when wild-type TP was expressed in HEK cells (D-E). Peak wild-type TP response to 0.5 or 1nM U46619 was 2.1-fold greater (P < .001; n = 8 replicates averaged in each trace with ± 21% error) than sham stimulation, whereas the peak TP-V241G response was not significantly different from sham stimulation.