PEX6
Pathology
germline mutations
- in complementation group 4 peroxisome biogenesis disorders (PBDs)
- in complementation group 6 peroxisome biogenesis disorders (PBDs)
Nota bene: Peroxisome biogenesis disorders (PBDs) (MIM.601539) include Zellweger syndrome (MIM.214100), infantile Refsum disease (MIM.266510), neonatal adrenoleukodystrophy (MIM.202370), and classic rhizomelic chondrodysplasia punctata (MIM.215100).
Somatic cell fusion complementation analysis indicates that the PBDs can be caused by defects in at least 11 different genes.
Because these disorders are associated with a peroxisomal protein sorting defect, a major focus of PBD research has been on the elucidation of the molecular mechanisms of protein import into peroxisomes.
Peroxisomal targeting signals (PTSs) are discrete amino acid sequences capable of directing proteins to the peroxisome.
Most peroxisomal matrix proteins contain PTS1, a C-terminal tripeptide of the sequence ser-lys-leu (SKL) or a conservative variant. In contrast, the N-terminal PTS2 consists of approximately 10 amino acids (arg/lys-leu-X5-gln/his-leu) and has been observed in only 3 peroxisomal proteins. The only documented human PTS2-containing proteins are peroxisomal thiolase (MIM.604054) and phytanic acid oxidase (MIM.266500).