UROS Gene (Uroporphyrinogen III Synthase)
Key enzyme in heme biosynthesis; mutations cause congenital erythropoietic porphyria (CEP).
Gene Information Card
| Symbol | UROS |
|---|---|
| Full Name | uroporphyrinogen III synthase |
| Gene Type | protein-coding |
| Chromosomal Location | 10q26.2 |
| NCBI Gene ID | 7390 ncbi.nlm.nih.gov/gene/7390 |
| Ensembl ID | ENSG00000188690 |
| UniProt ID | P10746 |
| OMIM ID | 606938 |
| HGNC ID | 12591 |
| Aliases | UROIIIS, UROS1 |
Description
The UROS gene encodes uroporphyrinogen III synthase (UROS), the fourth enzyme in the heme biosynthesis pathway. It catalyzes the cyclization of hydroxymethylbilane to uroporphyrinogen III, a key step in porphyrin metabolism. Mutations in UROS cause congenital erythropoietic porphyria (CEP, Günther disease), an autosomal recessive disorder characterized by severe photosensitivity, hemolytic anemia, and porphyrin accumulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital erythropoietic porphyria (CEP) | Loss-of-function mutations in UROS lead to deficient uroporphyrinogen III synthase activity, causing accumulation of uroporphyrinogen I and other porphyrins in erythrocytes, bone marrow, and tissues. This results in photosensitivity, blistering, hemolytic anemia, and erythrodontia. | ClinVar, OMIM |
| Porphyria, erythropoietic, UROS-related | Same mechanism as CEP; allelic heterogeneity with over 40 pathogenic variants reported. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Liver | 8.2 | Medium |
| Spleen | 6.1 | Low |
| Skin | 3.4 | Low |
| Whole blood | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (erythroleukemia) | 15.3 | High expression; relevant for erythropoiesis |
| HepG2 (hepatocellular carcinoma) | 9.8 | Moderate expression |
| HeLa (cervical carcinoma) | 5.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.217T>C (p.Cys73Arg) | Missense | ~30% of CEP alleles | Loss of function; disrupts active site |
| c.661C>T (p.Arg221Trp) | Missense | ~10% of CEP alleles | Loss of function; reduced enzyme stability |
| c.92-2A>G | Splice site | Rare | Splicing defect; loss of function |
| c.406C>T (p.Arg136*) | Nonsense | Rare | Premature stop; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most UROS mutations are loss-of-function, leading to reduced or absent uroporphyrinogen III synthase activity, causing CEP.
Gain of Function (GOF)
No gain-of-function mutations reported for UROS.
Dominant Negative (DN)
No dominant-negative mutations reported; CEP is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • uroporphyrinogen-III synthase activity (GO:0004852) | • protoporphyrinogen IX biosynthetic process (GO:0006782) |
| • 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 III synthase (UROS) is a 265-amino acid cytosolic enzyme that catalyzes the conversion of hydroxymethylbilane to uroporphyrinogen III, a critical step in heme synthesis. The protein adopts a two-domain structure with a central active site. Deficiency due to mutations leads to accumulation of non-physiological porphyrin isomers, causing congenital erythropoietic porphyria.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UROS Knockout HEK293 Cell Line | EDJ-KQ6004 | Human | 7390 | Details Get a Quote |
| UROS Knockout A-549 Cell Line | EDJ-KQ29608 | Human | 7390 | Details Get a Quote |
| UROS Knockout HCT 116 Cell Line | EDJ-KQ29609 | Human | 7390 | Details Get a Quote |
| UROS Knockout HeLa Cell Line | EDJ-KQ29610 | Human | 7390 | Details Get a Quote |
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