UROD Gene: Uroporphyrinogen Decarboxylase
Key enzyme in heme biosynthesis; mutations cause porphyria cutanea tarda and hepatoerythropoietic porphyria
Gene Information Card
| Symbol | UROD |
|---|---|
| Full Name | uroporphyrinogen decarboxylase |
| Gene Type | protein-coding |
| Chromosomal Location | 1p34.1 |
| NCBI Gene ID | 7389 ncbi.nlm.nih.gov/gene/7389 |
| Ensembl ID | ENSG00000126088 |
| UniProt ID | P06132 |
| OMIM ID | 613521 |
| HGNC ID | 12591 |
| Aliases | URO-D, UPD, UROD1 |
Description
The UROD gene encodes uroporphyrinogen decarboxylase, a cytosolic enzyme that catalyzes the fifth step in heme biosynthesis, converting uroporphyrinogen III to coproporphyrinogen III by decarboxylation of four acetate side chains. Deficiency of this enzyme leads to accumulation of uroporphyrinogen, resulting in porphyria cutanea tarda (PCT) and the more severe hepatoerythropoietic porphyria (HEP).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Porphyria cutanea tarda (PCT) | Reduced UROD activity (acquired or inherited) leads to accumulation of uroporphyrinogen in the liver, causing photosensitivity and skin fragility. | OMIM #176090; ClinVar |
| Hepatoerythropoietic porphyria (HEP) | Biallelic loss-of-function mutations in UROD cause severe deficiency, resulting in early-onset photosensitivity, hemolytic anemia, and liver dysfunction. | OMIM #176100; ClinVar |
| Uroporphyrinogen decarboxylase deficiency | Enzyme deficiency disrupts heme biosynthesis, leading to porphyrin accumulation and clinical porphyria. | NCBI Gene; UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Bone marrow | 8.3 | Medium |
| Kidney | 6.1 | Medium |
| Skin | 4.2 | Low |
| Spleen | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| K562 | 9.7 | Chronic myelogenous leukemia cell line |
| A549 | 5.4 | Lung carcinoma cell line |
| HeLa | 4.1 | Cervical adenocarcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.673C>T (p.Arg225Trp) | Missense | Common in PCT | Reduced enzyme activity |
| c.860G>A (p.Gly287Glu) | Missense | Rare in HEP | Severe loss of function |
| c.1053delG (p.Val352fs) | Frameshift | Rare | Complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Most UROD mutations result in partial or complete loss of enzymatic activity, leading to porphyrin accumulation.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect in heterozygous state, contributing to PCT.
View complete mutation data：
Gene Ontology (GO)
| • uroporphyrinogen decarboxylase activity (GO:0004853) | • heme biosynthetic process (GO:0006783) |
| • cytosol (GO:0005829) | • cytoplasm (GO:0005737) |
Pathways
• Heme biosynthesis (Reactome: R-HSA-189451)
• Porphyrin metabolism (KEGG: hsa00860)
Protein Summary
Uroporphyrinogen decarboxylase is a homodimeric cytosolic enzyme of 367 amino acids (40.8 kDa). It catalyzes the sequential decarboxylation of four acetate side chains of uroporphyrinogen III to yield coproporphyrinogen III. The enzyme requires no cofactors and is ubiquitously expressed, with highest levels in liver and erythroid tissues. Structural studies reveal a (β/α)8 barrel fold. Mutations that impair its activity underlie porphyria cutanea tarda and hepatoerythropoietic porphyria.
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