The genes for the human VPS10 domain-containing receptors are large and contain many small exons

The two human proteins with a VPS10 domain, SorLA and sortilin, both bind n europeptides. Searching for other VPS10-domain proteins in the database rev ealed three new putative human neuropeptide receptors. The new receptors we re designated SorCS1, SorCS2 and SorCS3, due to their identical domain comp osition, which, except for the N-terminal VPS10 domain, differs from that o f SorLA and sortilin. Using the databases of the human genome project we el ucidated the exon-intron structures of the human VPS10-receptor genes. They contain many short exons, separated by introns, several of which extend ov er more than 50 kb. The three SorCS genes encompass more than 500 kb of gen omic DNA and therefore represent some of the largest known human genes. All these genes map to chromosomal localisations of known genetic diseases, ma ny of them neurological disorders, corresponding to the strong expression o f these receptors in the brain. CpG islands are located in the first exon o f each of the VPS10-receptor genes and might be involved in developmental o r tissue-specific regulation of gene expression.