*4.2. ENPP1*

On the ClinVar database, there are nearly 100 ENPP1 pathological variants reported. These variants present a similar profile to that found in ABCC6, with a large majority being single nucleotide substitutions leading to missense, nonsense, splice site, and frameshift mutations, plus some deletions and duplications. The main consequence of these diseasecausing variants, which affects all critical parts of the protein, is the inactivation of the enzyme resulting in the failure to convert ATP (or ADP) into AMP and PPi. As NPP1 is the only enzyme that generates PPi, plasma levels drop to near zero in its absence [89].
