Abstract
Many retinal diseases are caused by mutations in photoreceptor-specific proteins. However, retinal disease can also result from mutations in widely expressed proteins. One such protein is inosine monophosphate dehydrogenase type 1 (IMPDH1), which catalyzes a key step in guanine nucleotide biosynthesis and also binds single-stranded nucleic acids. The pathogenic IMPDH1 mutations are in or near the CBS domains and do not affect enzymatic activity. However, these mutations do decrease the affinity and specificity of single-stranded nucleic acid binding. These observations suggest that IMPDH1 has a previously unappreciated role in RNA metabolism that is crucial for photoreceptor function.