A novel gene in the chromosomal region for juvenile myoclonic epilepsy on 6p12 encodes a brain-specific lysosomal membrane protein

Juvenile myoclonic epilepsy (JME) is the most frequent and, hence, most imp ortant form of hereditary grand mal epilepsy. Genetic linkage, haplotype, a nd recombination analyses have indicated that 6p11-12 (EJM1) is one of the candidate regions harboring a gene responsible for JME. In efforts to ident ify a gene responsible for JME, we identified several expressed sequences i n the EJM1 critical region. Here we report the identification and character ization of a gene, named C6orf33, in the EJM1 region. Northern blot analysi s showed that C6orf33 is predominantly expressed in brain but in mice, test is shows additional transcripts. C6orf33 is predicted to encode a novel sim ilar to 40-kDa membrane protein, LMPB1, that defines a novel protein family by having highly conserved orthologs in eukaryotes and three putative para logs in human. Biochemical and immunocytochemical studies revealed that LMP B1 is indeed an integral membrane protein that targets to lysosomal structu res. LAY-PBI may be involved in specialized lysosomal functions that are un ique to brain and testis, and the C6orf33 gene is of interest as a candidat e for EJM1. (C) 2001 Academic Press.