Fig. 2.

A: Schematic representation of the DEGS1 protein (UniProt ID O15121) displaying known variants of HLD18 (red lines). The new DEGS1 variants are depicted in grey (Patient 1, p.R311K and Patient 2, p.G270E). Putative transmembrane domains are depicted in blue. B: DEGS1 protein alignment of the C-terminal sequence containing the conserved amino acids mutated in the variants p.G270E and p.R311K (green and yellow). C: the location and clustering of single amino acid substitutions leading to HLD18 and the new DEGS1 variants within the predicted protein are shown. The dotted lined circle describes a sphere with a radius of 15 Å. Most variants are confined within the sphere as determined by the distance of the amide nitrogens to the nearest atom of the ceramide ligand, the space-filling model in green. Myr: myristoyl anchor at Gly1.