Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders

Human peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal-recessive diseases caused by mutations in PEX genes that encode peroxins, proteins required for peroxisome biogenesis. These lethal diseases include Zellweger syndrome (ZS), neonatal adrenoleukodystro-phy (NALD) and infantile Refsum's disease (IRD)1, three pheno-types now thought to represent a continuum of clinical features that are most severe in ZS, milder in NALD and least severe in IRD2. At least eleven PBD complementation groups have been identified by somatic-cell hybridization analysis2–6 compared to the eighteen PEX complementation groups that have been found in yeast. We have cloned the human PEX1 gene encoding a 147-kD member of the AAA protein family (ATPases associated with diverse cellular activities)7, which is the putative orthologue of Saccharomyces cerevisiae Pexlp (ScPexlp). Human PEX1 has been identified by computer-based ‘homology probing’ using the ScPexlp sequence to screen databases of expressed sequence tags (dbEST) for human cDNA clones. Expression of PEX1 rescued the cells from the biogenesis defect in human fibroblasts of complementation group 1 (CG1), the largest PBD complementation group. We show that PEX1 is mutated in CG1 patie