Figure 2.

The CAPN5 gene harbors a novel mutation in domain II. (A) CAPN5 is composed of four domains, and the novel mutation was located in catalytic domain II (violet). (B) Primary protein sequence alignment of calpain-5 orthologs shows 70% evolutionary conservation of the new mutated p.Arg289Trp residue, along with the three prior ADNIV mutations, p.Arg243Leu, p.Leu244Pro, and p.Lys250Asn (magenta arrow), in catalytic domain IIb. (C) Alignment of 13 human calpain family paralogs show the p.Arg289Trp is poorly conserved (15%).