CPOX Gene: Coproporphyrinogen Oxidase
Genetic and Functional Insights into Heme Biosynthesis and Porphyria
Gene Information Card
| Symbol | CPOX |
|---|---|
| Full Name | Coproporphyrinogen Oxidase |
| Gene Type | Protein coding |
| Chromosomal Location | 3q12.1 |
| NCBI Gene ID | 1371 ncbi.nlm.nih.gov/gene/1371 |
| Ensembl ID | ENSG00000180819 |
| UniProt ID | P36551 |
| OMIM ID | 121300 |
| HGNC ID | 2321 |
| Aliases | CPO, CPX, HCP |
Description
The CPOX gene encodes coproporphyrinogen oxidase, a mitochondrial enzyme that catalyzes the sixth step in the heme biosynthesis pathway, converting coproporphyrinogen III to protoporphyrinogen IX. Mutations in CPOX cause hereditary coproporphyria (HCP), an autosomal dominant disorder characterized by acute neurovisceral attacks and photosensitivity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Coproporphyria (HCP) | Loss-of-function mutations in CPOX reduce coproporphyrinogen oxidase activity, leading to accumulation of coproporphyrinogen III and its oxidized product coproporphyrin in urine and feces. This disrupts heme synthesis and triggers acute attacks. | ClinVar, OMIM |
| Harderoporphyria | Specific CPOX mutations (e.g., p.Lys404Glu) cause a variant form of HCP with neonatal hemolytic anemia and skin lesions due to accumulation of harderoporphyrin. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 18.5 | Medium |
| Bone Marrow | 12.3 | Medium |
| Kidney | 9.8 | Low |
| Heart | 6.2 | Low |
| Brain | 3.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocyte cell line |
| K562 | 22.7 | Erythroleukemia cell line |
| HEK293 | 8.4 | Embryonic kidney cell line |
| HeLa | 5.6 | Cervical cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.127C>T (p.Arg43Trp) | Missense | <0.01% | Reduced enzyme activity; associated with HCP |
| c.1210A>G (p.Lys404Glu) | Missense | <0.01% | Causes harderoporphyria; altered substrate specificity |
| c.991C>T (p.Arg331Trp) | Missense | <0.01% | Loss of function; HCP |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Complete loss of protein; severe HCP |
Mutation functional classification
Loss of Function (LOF)
Most CPOX mutations are loss-of-function, reducing or abolishing coproporphyrinogen oxidase activity, leading to substrate accumulation and hereditary coproporphyria.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CPOX.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by interfering with dimerization or mitochondrial targeting, though haploinsufficiency is the primary mechanism in HCP.
View complete mutation data：
Gene Ontology (GO)
| • Coproporphyrinogen oxidase activity (GO:0004109) | • Protoporphyrinogen IX biosynthetic process (GO:0006782) |
| • Heme biosynthetic process (GO:0006783) | • Mitochondrion (GO:0005739) |
| • Oxidoreductase activity (GO:0016491) |
Pathways
• Heme biosynthesis (Reactome: R-HSA-189451)
• Porphyrin and chlorophyll metabolism (KEGG: hsa00860)
Protein Summary
Coproporphyrinogen oxidase is a homodimeric mitochondrial enzyme (mature form ~37 kDa) that catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX. It requires molecular oxygen and is essential for heme production. The protein contains a conserved flavin-binding domain and is highly expressed in erythroid tissues and liver.
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