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

Abstract

Juvenile myoclonic epilepsy (JME) is the most frequent and, hence, most important form of hereditary grand mal epilepsy. Genetic linkage, haplotype, and recombination analyses have indicated that 6p11-12 (EJM1) is one of the candidate regions harboring a gene responsible for JME. In efforts to identify a gene responsible for JME, we identified several expressed sequences in the EJM1 critical region. Here we report the identification and characterization of a gene, named C6orf33, in the EJM1 region. Northern blot analysis showed that C6orf33 is predominantly expressed in brain but in mice, testis shows additional transcripts. C6orf33 is predicted to encode a novel ∼40-kDa membrane protein, LMPB1, that defines a novel protein family by having highly conserved orthologs in eukaryotes and three putative paralogs in human. Biochemical and immunocytochemical studies revealed that LMPB1 is indeed an integral membrane protein that targets to lysosomal structures. LMPB1 may be involved in specialized lysosomal functions that are unique to brain and testis, and the C6orf33 gene is of interest as a candidate for EJM1.