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. 2015 May 6;23(11):1473–1481. doi: 10.1038/ejhg.2015.71

Figure 4.

Figure 4

Features of the three missense variants identified in DYRK1A. (a) The pedigree of three families with missense variants. (b) The Sanger sequencing traces of two of these variants. (c) Amino-acid alignments at the variant position (red box) and surrounding bases across 16 species as indicated on the left. (d) Overview of the human DYRK1A protein structure (PDB ID: 4MQ1). The active site (inset) is sandwiched between the N-terminal (blue) and C-terminal lobes (red), which are connected by a short hinge segment (green). The three residues mutated in patients (Lys188, Leu245, and Leu295) and the ATP (modeled from PDB ID: 1ATP) are shown as ball-and-stick configuration colored by atom. Lys188 coordinates (black dashed lines) the α- and β-phosphates of ATP. (e, f) Steric clashes caused by variants of Leu295Phe and Leu245Arg in relation to the active site. (e) Leu295Phe variant (magenta) causes a clash with Leu248 (red). (f) Leu245Arg (magenta) causes a clash with Ile303 (orange) and Ile293 (orange).