Figure 2.

(A) Schematic representation of the MMP21 gene and the MMP21 protein. Exons are depicted in blue and introns in light blue. Protein domains are represented in different colors and aminoacidic positions at the beginning and end of each domain are reported. Missense variants identified in the literature are reported. (B) Structural model of MMP21 as predicted by AlphaFold (XZ plane). Protein backbone is represented in gray, while domains are reported in the same color as Figure 2A (i.e., ZnMc domain in green and HX domains in pink). Aminoacidic positions in which missense variants occur are colored in red in the 3D structure. (C) Backbone of the ZnMc domain of MMP21 is reported in green. Positions in which missense variants occur are colored in red and amino acid structures are highlighted (carbon atoms are depicted in grey, oxygen in red, nitrogen in blue, and sulfur in yellow). (D) Protein alignment showing conservation of methionine 301 across species, highlighted by the red frame; amino acids with similar physicochemical properties are represented in the same colors, as defined by the Clustal Omega software. (ZnMc: Zinc-dependent metalloprotease; HX: Hemopexin-like repeats). In figures, the variant identified in our patients, c.903G>A, p.(Met301Ile), is reported in red.