Protein sequence alignment and domains. (a) Alignment of KRT25 protein sequence using Clustal Omega. Positions with a fully conserved residue (asterisks) or a conservation of strongly similar (colons) as well as weakly similar properties (periods) between groups are displayed. The missense variant R89H occurs in a highly conserved region. (b) Predicted protein domain of KRT25. The variant R89H is located in the intermediate filament protein domain. (c) Alignment of SP6 protein sequence using Clustal Omega. The missense variant G364S is also located in a conserved region. (d) Predicted protein domain of SP6. The variant G364S is can be found distal of the FOG:Zn-finger domain.