Figure 3.

Structural effects in ATP21B1

(A) Structure of ATP2B1 (PDB: 6A69¹⁹) indicating the sites of genetic variants. The ATP2B1 structure is shown as blue ribbon and the neuroplastin subunit in green. Sites of genetic variants are shown in space-filled presentation (atom-type coloring) and labeled. The location of the membrane is indicated by two dotted lines.

(B) Enlargement of the ATP2B1 structure showing the effect of the p.T264Ile and p.Gln857Arg variants. (B) T264 forms a hydrogen bond (green dotted line) to L261.

(C) In the p.Thr264Ile variant, this hydrogen bond cannot be formed by the nonpolar isoleucine sidechain.

(D) Q857 is in close spatial proximity to M928 (shown in gray).

(E) The bulkier R857 sidechain of the variant causes steric clashes (red dotted circle) with M928 leading to a destabilization of ATP2B1.