Fig. 2: Molecular modeling.

Locations of the variants in MINPP1 gene (a) and protein (b). Model of the MINPP1 structure (c–h) illustrating the effect of truncation and missense variants and the ___location of the variants on the gene. c Structure of MINPP1 (backbone representation) showing the ___location of p.A284 (blue) and the bound InsP₆ substrate (stick representation). Also, the p.Arg404* truncation variant causes the loss of several elements in secondary structure (missing elements are indicated in cyan). d Structure of MINPP1 (backbone representation) showing the ___location of p.Iso331 (blue) and the bound InsP₆ substrate (stick representation). e p.Ala284 is buried in the hydrophobic core of MINPP1. p.Ala284 is colored according to the atom types and the interacting hydrophobic residues are shown in dark gray. f In the p.Ala284Asp variant a charged carboxyl group is placed within the hydrophobic protein core (color coding as in (e)). f and g p.Iso331 forms tight hydrophobic interactions with the aromatic residues p.Phe235 and p.Tyr329, and with the hydrophobic methylene groups of the p.Glu474 sidechain. p.Iso331 is colored according to the atom types and the interacting residues are shown in dark gray. h In the p.Iso331Ser variant the smaller polar serine sidechain is placed within the hydrophobic environment leading to a destabilization of the MINPP1 structure (color coding as in (g)).