An opsin-related gene encodes a putative RPE-retinal G-protein-coupled receptor (RGR) that is most homologous to the visual pigments and invertebrate retinochrome. A splice variant of human RGR mRNA can be demonstrated by the sequence of isolated cDNA clones and by the amplification and analysis of human retinal mRNA. The shortened transcript contains a deletion of 114 nucleotides that correspond exactly to the sequence of exon 6 in the human rgr gene. The predicted RGR variant lacks the putative sixth transmembrane domain and has a calculated molecular weight of 27,726. Variable amounts of a 28-kDa protein were found in the retinas of some individuals by immunoblot assay. Since a similar shortened RGR transcript was not detected in bovine retina or RPE, the RGR variant is not essential for vertebrate vision. Analysis of the structure of the rgr gene and of the sequences of cDNA clones indicates that the truncated mRNA may be produced through alternative splicing of pre-mRNA from which a cassette exon is removed and the predicted RGR variant is radically altered in primary structure.