Figure 5.

Location of rare TLR7 variants within TLR7 protein domains

(A) Rare, deleterious TLR7 variants (POP_lowrisk, C10+M1, MAF <0.1%) are mapped on the protein domains of TLR7 (x axis: amino acid position). Phenotype, according to the POP_lowrisk case-control definition, and the sex of variant carriers is indicated by color or caption. Variants of carriers previously reported in Asano et al.¹⁹ (see subjects and methods and Table S2) are indicated by asterisks (∗). TLR7 domains: LRR-NT (leucine-rich repeat, N terminal, aa 27–65) orange; LRR regions 1–26 (aa 66–786) blue; LRR-CT (leucine-rich repeat, C terminal, aa 787–839), violet; TIR (Toll/interleukin-1 receptor) domain (aa 889–1033), green.

(B) TLR7 dimer overview, interface highlighted as gray surface (also in C).

(C) Non-synonymous variants from (A) are highlighted in the 3D conformation of one TLR7 subunit (PDB ID: 5GMH) and are presented from two angles. Phenotype (POP_lowrisk, see A) and sex of the variant carriers are indicated by color coding. Variants within 5 Ångström of the subunit interface are highlighted by a hash (#, also in A). Variants located downstream of position T858 could not be plotted due to absence of the respective residues from the structure. Visualized using PyMOL Molecular Graphics System (Version 2.5.5 Schrödinger, LLC).