Relative cell death of U937 expressing NLRP3 variants as compared with U937 expressing WT NLRP3 in response to NLRP3 expression, priming, and/or activation. Regression coefficient (RC) heatmap from the glmm for each variant as compared with the WT. Positive RC denotes increased cell death in the considered variant as compared with the WT, and conversely. For significant values (P < 0.05), RC corresponding to increases (magenta) or decreases (cyan) in cell death are color-coded. In gray, not significant values (P > 0.05) correspond to conditions (variant * treatment * time point) in which the percentage of dead cells among U937 expressing NLRP3 variant is not statistically different from those among U937 expressing WT NLRP3. Based on the results, variants are classified into five functional groups: constitutive active variants (group#5, red), variants active upon either priming or activation signal (group#4, green), variants active upon priming signal (group#3, yellow), variants active upon activation signal (group#2, blue), and mutants active upon priming and activation signals (no gain-of-function, group#1, black). Results of two to eight independent experiments done in duplicates.