PPOX
Function
Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX.
Involvement in disease
Variegate porphyria
VP
A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Variegate porphyria is an acute hepatic form characterized by partial reduction of protoporphyrinogen oxidase activity, increased photosensitivity, skin blistering and scarring of sun-exposed areas, skin hyperpigmentation, abdominal pain, and neuropsychiatric symptoms. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease. Inheritance is autosomal dominant with incomplete penetrance.
None
The disease is caused by variants affecting the gene represented in this entry. Mutations leading to severe PPOX deficiency cause the rare homozygous variant form of VP. Missense mutations that preserve 10%-25% of wild-type activity may not cause clinically overt VP in heterozygotes (PubMed:9811936). Mutations with intermediate effect on catalytic activity may cause VP, but with a low clinical penetrance (PubMed:10486317).
Variegate porphyria, childhood-onset
VPCO
An autosomal recessive form of variegate porphyria, a disorder of heme biosynthesis that results from diminished activity of protoporphyrinogen oxidase. VPCO is characterized by severe protoporphyrinogen oxidase deficiency, onset of photosensitization by porphyrins in early childhood, skin scarring and hyperpigmentation, and skeletal abnormalities of the hand. Additional variable features are short stature, impaired intellectual development, and seizures. VPCO patients rarely experience acute neuropsychiatric or abdominal attacks.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; protoporphyrin-IX from protoporphyrinogen-IX: step 1/1.
Sequence Similarities
Belongs to the protoporphyrinogen/coproporphyrinogen oxidase family. Protoporphyrinogen oxidase subfamily.
Tissue Specificity
Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
Cellular localization
- Mitochondrion inner membrane
- Peripheral membrane protein
- Intermembrane side
Alternative names
Protoporphyrinogen oxidase, PPO, PPOX