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 (βxy = 0.16; Pxy = 9.7 × 10−6). Color shows linkage disequilibrium with the missense variant rs721917. d, Three cartoon views of an AlphaFold 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 colored red and blue respectively, and the sulfur atom is colored yellow. Credit: Nature (2023). DOI: 10.1038/s41586-023-06034-3">
功能基因组学分析SLC22A31和SFTPD。一个,对多个变量的影响效果的情节SLC22A31表达式(eQTLgen,x轴)对增加对关键COVID-19 (βxy= 0.11;Pxy= 1.3×10−9)。颜色显示连锁不平衡(LD) rs117169628错义变体。b,三个卡通视图AlphaFold模型假定的溶质载体家庭22个成员31 (SLC22A31;UniProtKB:A6NKX4)。Pro474,相互作用的氨基酸的侧链是显示为连接领域。一个公认的小分子在细胞膜运输通道是由虚线圈表示。Pro474预测是位于跨膜螺旋和指向一个假定的小分子的运输途径。风险变异,P474L rs117169628 (Ala)将引入更多的灵活性的跨膜螺旋,因此可能影响SLC22A31的传输特性。Pro474预测是在紧密的环境中,并可能因此影响SLC22A31的折叠。c,效果影响的多个变种SFTPD表达式(eQTLgen,x轴)对增加对关键COVID-19 (βxy= 0.16;Pxy= 9.7×10−6)。颜色显示与错义突变rs721917连锁不平衡。d,三个卡通视图AlphaFold模型肺surfactant-associated蛋白D (SFTPD;UniProtKB:P35247)。侧链的变体Met31显示为连接领域。Met31预测是位于SFTPD secondary-structure-lacking地区。在右边的图,氧和氮原子分别颜色红色和蓝色和黄色的硫原子。信贷:自然(2023)。DOI: 10.1038 / s41586 - 023 - 06034 - 3
