title: Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome biogenesis disorders.
abstract: The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous diseases lethal in early infancy. Although the clinical features of PBD patients may vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins. This cellular phenotype is shared by yeast pex mutants, and human orthologues of yeast PEX genes have been shown to be defective in some groups of PBD patients. We identified a putative human orthologue of ScPEX12 by screening the database of expressed sequence tags for cDNAs capable of encoding a protein similar to yeast Pex12p. Although its sequence similarity to yeast Pex12 proteins was limited, PEX12 shared the same subcellular distribution as yeast Pex12p and localized to the peroxisome membrane. PEX12 expression restored peroxisomal protein import in fibroblasts from PBD patients of complement group 3 (CG3) and frameshift mutations in PEX12 were detected in two unrelated CG3 patients. These data demonstrate that mutations in PEX12 are responsible for CG3 of the PBD and that PEX12 plays an essential role in peroxisomal matrix protein import.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Chang
authors.forename: W H
authors.initials: WH
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Moser
authors.forename: D
authors.initials: D
authors.lastname: Valle
authors.forename: S J
authors.initials: SJ
authors.lastname: Gould
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts; D016368:Frameshift Mutation / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D008830:Microbodies / Q000737:chemistry; D008969:Molecular Sequence Data; D018901:Peroxisomal Disorders / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; C105251:PEX12 protein, human