Supplementary Table S3.

IL-36Ra Residues that are Most Intolerant to Substitutions

Rhapsody Stability Analysis		mCSM Affinity Analysis
Residue	Pathogenicity Score1	Residue	Pathogenicity Score2
Phe98	0.81	Phe151	−1.67 (C)
Phe100	0.78	His22	−1.64 (C)
Cys122	0.78	Asn23	−1.56 (C)
Val44	0.76	Tyr116	−1.22
Trp119	0.75	Cys122	−1.17
Leu59	0.75	Arg102	−1.12 (C)
Leu121	0.74	Gln152	−1.10 (C)
Cys67	0.74	Arg48	−1.01
Pro56	0.73	Glu112	−1.01
Leu19	0.72	His32	−0.98 (C)
Gly34	0.72	Val57	−0.96
Ala6	0.72	Pro76	−0.90
Pro117	0.71	Trp49	−0.90
Gly5	0.71	Cys154	−0.87 (C)
Gly60	0.71	Cys70	−0.87

¹Average pathogenicity likelihood across all 19 possible substitutions.

²ΔΔG measured by Ala scanning (kcal/mol); C, IL-36R/IL-36Ra contact residue.