Fig. 5: Protein expression alterations and corresponding druggability.

A A series of density plots illustrating the differences in protein expression levels between mutation carriers and non-carriers. P-values are two-sided, adjusted by the false discovery rate. The black lines in each plot indicate the median protein expression level for each group. It’s noteworthy that protein expression data is available for only 16 of the identified genes. B MR analysis to discern the causal link between protein expression levels and IMDs. GWAS analyses were first performed on protein expression, followed by the selection of SNPs from GWAS as instrumental variables. The point’s edge color represents the negative logarithm of the FDR P-value, whereas the interior color stands for the coefficient. IVW was selected as the prior method for MR. C Gene plots displaying the protein-coding variants that contribute to the amino-acid signals for four protein entities (CBLB, DHX3, CIITA, and CAPN9). The protein domains and missense-constrained regions of the gene are also labeled. IMD immune-mediated disease, GWAS genome-wide association study, SNP single nucleotide polymorphism, FDR false discovery rate, MR Mendelian randomization, IVW inverse-variance weighted, AD atopic dermatitis, Celiac Celiac disease, PA pernicious anemia, Crohn Crohn’s disease, Graves Graves’ disease, SD sarcoidosis, MG myasthenia gravis, HPT autoimmune hypothyroidism, PBC primary biliary cirrhosis.