Fig. 1

Human TMEM173 gene and its associated diseases. a Cartoon illustrates human TMEM173 gene (NCBI Reference Sequence: NC_000005.10). The common SNPs (R71H, G230A, R232H, and R293Q) are annotated along with the disease-associated SNPs (rs7447927 and rs13181561) identified in the published GWAS [28, 37]. b An annotation of the functional domains in the human STING protein [3,4,5, 23, 75, 76]. TM transmembrane region, CDN cyclic dinucleotide. Amino acids important for the CDN binding were in black. Common human STING variants were in green. Amino acids important for IRF3 activation were in blue. SAVI mutations were in red. c The structure of a human STING dimer anchored on the ER membrane [4, 23]. The cytoplasmic tails of the STING dimer form a butterfly-like binding pocket for CDN. The common STING variants G230A and R232H locate on the top (the lid region) of the binding pocket. The R293Q variant locates at the bottom of the pocket. The R71H variant locates in a predicted cytoplasmic loop facing the bottom of the binding pocket. The SAVI mutations V147M, N154S and V155M locate in the stem region of the binding pocket