Human peroxisome assembly factor-2 (PAF-2): a gene responsible for group C peroxisome biogenesis disorder in humans

Am J Hum Genet. 1996 Dec;59(6):1210-20.


Peroxisome-biogenesis disorders (PBD) are genetically heterogeneous and can be classified into at least ten complementation groups. We recently isolated the cDNA for rat peroxisome assembly factor-2 (PAF-2) by functional complementation using the peroxisome-deficient Chinese-hamster-ovary cell mutant, ZP92. To clarify the novel pathogenic gene of PBD, we cloned the full-length human PAF-2 cDNA that morphologically and biochemically restores peroxisomes of group C Zellweger fibroblasts (the same as group 4 in the Kennedy-Krieger Institute) and identified two pathogenic mutations in the PAF-2 gene in two patients with group C Zellweger syndrome. The 2,940-bp open reading frame of the human PAF-2 cDNA encodes a 980-amino-acid protein that shows 87.1% identity with rat PAF-2 and also restored the peroxisome assembly after gene transfer to fibroblasts of group C patients. Direct sequencing of the PAF-2 gene revealed a homozygous 1-bp insertion at nucleotide 511 (511 insT) in one patient with group C Zellweger syndrome (ZS), which introduces a premature termination codon in the PAF-2 gene, and, in the second patient, revealed a splice-site mutation in intron 3 (IVS3+1G-->A), which skipped exon 3, an event that leads to peroxisome deficiency. Chromosome mapping utilizing FISH indicates that PAF-2 is located on chromosome 6p21.1. These results confirm that human PAF-2 cDNA restores peroxisome of group C cells and that defects in the PAF-2 produce peroxisome deficiency of group C PBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adenosine Triphosphatases / analysis
  • Adenosine Triphosphatases / genetics*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 6 / genetics*
  • Cloning, Molecular
  • DNA, Complementary / genetics*
  • Female
  • Genetic Complementation Test
  • Humans
  • Infant
  • Microbodies / genetics*
  • Molecular Sequence Data
  • Mutagenesis, Insertional / genetics*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Rats
  • Sequence Deletion*
  • Transfection
  • Zellweger Syndrome / genetics*


  • DNA, Complementary
  • RNA, Messenger
  • Adenosine Triphosphatases
  • ATPases Associated with Diverse Cellular Activities
  • PEX6 protein, human
  • Pex6 protein, rat

Associated data

  • GENBANK/D83703