title: The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein.
abstract: The neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive neurodegenerative diseases characterized by the accumulation of autofluorescent lipopigment in various tissues and by progressive cell death in the brain and retina. The gene for variant late-infantile NCL (vLINCL), CLN6, was previously mapped to chromosome 15q21-23 and is predicted to be orthologous to the genes underlying NCL in nclf mice and in South Hampshire and Merino sheep. The gene underlying this disease has been identified with six different mutations found in affected patients and with a 1-bp insertion in the orthologous Cln6 gene in the nclf mouse. CLN6 encodes a novel 311-amino acid protein with seven predicted transmembrane domains, is conserved across vertebrates and has no homologies with proteins of known function. One vLINCL mutation, affecting a conserved amino acid residue within the predicted third hydrophilic loop of the protein, has been identified, suggesting that this domain may play an important functional role.
authors.affiliation: Department of Paediatrics and Child Health, Royal Free and University College Medical School, University College London, London, United Kingdom. ruth.wheeler@ucl.ac.uk
authors.forename: Ruth B
authors.initials: RB
authors.lastname: Wheeler
authors.forename: Julie D
authors.initials: JD
authors.lastname: Sharp
authors.forename: Roger A
authors.initials: RA
authors.lastname: Schultz
authors.forename: John M
authors.initials: JM
authors.lastname: Joslin
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Williams
authors.forename: Sara E
authors.initials: SE
authors.lastname: Mole
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics*; D010641:Phenotype; D017434:Protein Structure, Tertiary; D022821:RNA Splice Sites / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016415:Sequence Alignment
chemical_list: C447500:CLN6 protein, human; C486722:Cln6 protein, mouse; D008565:Membrane Proteins; D022821:RNA Splice Sites; D012333:RNA, Messenger