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. 2023 May 17;617(7962):764–768. doi: 10.1038/s41586-023-06034-3

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© The Author(s) 2023, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a, Effect-size plot for the effect of multiple variants on SLC22A31 expression (eQTLgen, x axis) against increasing susceptibility to critical COVID-19 (β_xy = 0.11; P_xy = 1.3 × 10⁻⁹). The colour shows linkage disequilibrium (LD) with the missense variant rs117169628. b, Three cartoon views of an AlphaFold²² model of putative solute carrier family 22 member 31 (SLC22A31; UniProtKB: A6NKX4). The side chains of Pro474 and interacting amino acids are shown as connected spheres. A putative channel for small-molecule transport across the cell membrane is indicated by a dashed circle. Pro474 is predicted to be located in the transmembrane helix and point towards a putative transport pathway of a small molecule. The risk variant, P474L (Ala at rs117169628) would be expected to introduce more flexibility to the transmembrane helix and might therefore affect the transport properties of SLC22A31. Pro474 is predicted to be in a tightly packed environment, and may therefore affect the folding of SLC22A31. c, Effect-size plot for effect of multiple variants on SFTPD expression (eQTLgen, x axis) against increasing susceptibility to critical COVID-19 (β_xy = 0.16; P_xy = 9.7 × 10⁻⁶). Colour shows linkage disequilibrium with the missense variant rs721917. d, Three cartoon views of an AlphaFold²² model of pulmonary surfactant-associated protein D (SFTPD; UniProtKB: P35247). The side chain of the variant Met31 is shown as connected spheres. Met31 is predicted to be located in the secondary-structure-lacking region of SFTPD. In the diagram on the right, oxygen and nitrogen atoms are coloured red and blue respectively, and the sulfur atom is coloured yellow.