Peroxisomes are small, single-membrane organelles present in most eukaryotic cells. These organelles contain peroxidases and other enzymes involved in several key metabolic processes such as free radical detoxification, lipid catabolism and biosynthesis, and hydrogen peroxide metabolism. In humans, the PEX16 gene encodes Peroxisome Biogenesis Factor 16, a protein that forms an integral component of the peroxisomal membrane. This protein is believed to play a role in peroxisome organization, peroxisome membrane biogenesis and protein import into the peroxisome matrix. It has been found that the C-terminal region of PEX16, which is cytoplasmically exposed, is involved in peroxisome formation, while the first transmembrane domain and the positively charged region between amino acids 66-81 are responsible for peroxisome targeting.
The gene is associated with the Peroxisome Biogenesis Disorders 8A and 8B (PBD8A & PBD8B). PBD8A, also known as Zellweger syndrome, is characterized by profound hypotonia, seizures and craniofacial anomalies. Most affected patients succumb to the disorder within the first year of life. PBD8B is a milder condition and is characterized by neonatal adrenoleukodystrophy and infantile refsum disease. Affected patients may require wheelchairs for movement and suffer from developmental delay, hypotonia and visual impairment.
The PEX16 gene is located on the short arm of chromosome 11. It spans a length of just 9 kb of DNA and its coding sequence is contained in 12 exons. The protein product encoded by this gene has a molecular mass of 38 kDa and consists of 336 amino acids. An additional isoform of the PEX16 protein exists due to alternative splicing and contains 346 amino acids. The gene is found to be overexpressed in the lungs and bones. Homozygous mutations in the PEX16 gene associated with PBD8A and PBD8B include missense mutations, splice site mutations and frameshift and premature truncations.