For example, the missense mutations on R71, V382, R391, L414, N417, S445, and R450 was reported in HPP patients with dominant negative effect and symptom from moderate to severe21,26–28 (Fig. 1f and Supplementary Data 1), implying the importance of dimerization in TNAP function (Fig. 1c). Here, ALPL is linked to hypophosphatasia.