Comparative analysis of aryl-hydrocarbon receptor interacting protein-like1 (Aipl1), a gene associated with inherited retinal disease in humans

Mutations in AIPL1 cause Leber congenital amaurosis (LCA), the most severe form of inherited blindness in children; however, the function of this prot ein in normal vision remains unknown. To determine amino acid subsequences likely to be important for function, we have compared the protein sequence of several species. Sequence conservation is highest across the three Aip11 tetratricopeptide (TPR) motifs and extends across the protein, except for a proline-rich amino acid sequence present only at the C-terminus of primat e Aip11. The length of the proline-rich region varies within primates; howe ver, the length differences between human and primate Aip11 do not correlat e with evolutionary distance. These observations reinforce the importance o f the TPR domains for function, the similarity of Aip11 to a family of prot eins that act as molecular chaperones, and the importance of comparative se quencing data for determination of whether AIPL1 sequence variants in patie nts are likely to cause retinopathy.