PPOX Gene - Protoporphyrinogen Oxidase
Genetic and Functional Insights into PPOX, a Key Enzyme in Heme Biosynthesis
Gene Information Card
| Symbol | PPOX |
|---|---|
| Full Name | Protoporphyrinogen Oxidase |
| Gene Type | Protein coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 5498 ncbi.nlm.nih.gov/gene/5498 |
| Ensembl ID | ENSG00000143224 |
| UniProt ID | P50336 |
| OMIM ID | 600923 |
| HGNC ID | 9280 |
| Aliases | VP, PPO, V-PORPHYRIA |
Description
The PPOX gene encodes protoporphyrinogen oxidase (PPO), the penultimate enzyme in the heme biosynthesis pathway. PPO catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX. Mutations in PPOX cause variegate porphyria (VP), an autosomal dominant disorder characterized by acute neurovisceral attacks and photosensitivity. The enzyme is localized to the mitochondrial inner membrane and is widely expressed.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Variegate Porphyria (VP) | Loss-of-function mutations in PPOX reduce protoporphyrinogen oxidase activity, leading to accumulation of porphyrin precursors and photosensitizing porphyrins. | ClinVar, OMIM |
| Porphyria Cutanea Tarda (PCT) (rare association) | Secondary deficiency or modifier effects; not primary cause. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Bone Marrow | 8.3 | Medium |
| Kidney | 6.1 | Low |
| Heart | 4.7 | Low |
| Brain | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| K562 | 9.8 | Chronic myelogenous leukemia |
| HeLa | 5.4 | Cervical adenocarcinoma |
| A549 | 4.1 | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.673C>T (p.Arg225Trp) | Missense | Common in VP | Reduced enzyme activity |
| c.1082C>T (p.Pro361Leu) | Missense | Rare | Loss of function |
| c.1A>G (p.Met1Val) | Start loss | Rare | No protein synthesis |
| c.997_999del (p.Phe333del) | Deletion | Rare | Frameshift, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most PPOX mutations result in partial or complete loss of protoporphyrinogen oxidase activity, causing accumulation of porphyrin precursors.
Gain of Function (GOF)
No gain-of-function mutations reported for PPOX.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by interfering with dimerization or mitochondrial targeting.
View complete mutation data：
Gene Ontology (GO)
| • protoporphyrinogen oxidase activity (GO:0004729) | • protoporphyrinogen IX biosynthetic process (GO:0006782) |
| • mitochondrion (GO:0005739) | • heme biosynthetic process (GO:0006783) |
| • oxidoreductase activity (GO:0016491) |
Pathways
• Heme biosynthesis (KEGG: hsa00860)
• Porphyrin and chlorophyll metabolism (KEGG: hsa00860)
Protein Summary
Protoporphyrinogen oxidase (PPO) is a 477-amino acid flavoprotein located on the inner mitochondrial membrane. It catalyzes the six-electron oxidation of protoporphyrinogen IX to protoporphyrin IX, a critical step in heme production. The enzyme functions as a homodimer and requires FAD as a cofactor. Deficiency leads to variegate porphyria.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPOX Knockout HEK293 Cell Line | EDJ-KQ5517 | Human | 5498 | Details Get a Quote |
| PPOX Knockout A-549 Cell Line | EDJ-KQ27517 | Human | 5498 | Details Get a Quote |
| PPOX Knockout HCT 116 Cell Line | EDJ-KQ28765 | Human | 5498 | Details Get a Quote |
| PPOX Knockout HeLa Cell Line | EDJ-KQ28766 | Human | 5498 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
