Fig. 1.

ELOVL4 (A) and its translated protein (B) showing the location of the various mutations (A-B). All STGD3 causing mutations (orange) in exon 6 lead to a truncated protein, resulting in the loss of the ER retention motif. The two mutations in the promoter region of ELOVL4 downregulate ELOVL4 expression based on luciferase activity and cause STGD3. Most of the SCA34 ELOVL4 (black) mutations cluster in the exon 4 region, except for an exon 6 mutation that produces a full-length protein with a single amino acid substitution. Homozygous mutations (red) produce an even more severe truncation of the protein, with an exon 1 mutation lacking the catalytic motif and ER retention motif. None of the mutations occur in the active region of ELOVL4, yet the STGD3 5 bp deletion mutant is enzymatically inactive due to loss of the ER targeting motif.