Figure 3.

Distribution and predicted structural effects of SPATA5L1 variants

(A) Alternative splicing leads to two distinct SPATA5L1 transcripts (top), resulting in a full-length and short isoform (bottom). The variant numbering is based on the full-length transcript and isoform, GenBank: NM_024063.3 and GenBank: NP_076968.2. Non-coding and coding regions of exons are denoted by flat-edged and pointed-edged rectangles, respectively.

(B) Structural effects of a subset of variants identified in this study were evaluated with a three-dimensional model of SPATA5L1 based on the structure of the homologous ATPase p97 (PDB: 5FTN). The SPATA5L1 structure is shown in ribbon presentation, depicting the N-terminal domain (green) and two conserved ATPase domains (AAA, blue and cyan). ATP ligands are shown in stick presentation. Altered residues are highlighted as balls and labeled. Red and orange balls indicate variants that were classified as deleterious by two or one methods, respectively. Yellow balls indicate variants that were predicted to have little effect on protein structure. The variants depicted in more detail in Figure S3 are labeled in bold letters.