Extended Data Fig. 6: Functional genomics analyses for TYK2.

(a) Effect size plot for effect of multiple variants on TYK2 expression (eQTLgen, x-axis) against increasing susceptibility to critical COVID-19 (\({\beta }_{{xy}}\) = 0.53; \({P}_{{xy}}=1.2\times {10}^{-23}\)). Colour shows linkage disequilibrium (LD) with the missense variant rs34536443. (b) Crystal structure of TYK2 kinase domain (Protein Data Bank ID 4GVJ³⁹) in two views that differ by a 45° rotation around a horizontal axis. The side chain of P1104 is shown as connected spheres with a nitrogen atom coloured in blue. Carbon, oxygen, nitrogen and phosphorus atoms of ATP are shown as magenta, red, blue and orange connected spheres, respectively. The N-terminal region of the kinase domain is not shown in the second view for clarity. The right-most panel shows a close view of P1104 and neighbouring residues with their side chains shown as sticks. Numbering of residues corresponds to UniProtKB entry P29597. P1104 is in the catalytic kinase domain and proximal to the ATP-binding site; TYK2 P1104A is catalytically impaired⁴⁰.