Catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrinogen III, the branch point for the various sub-pathways leading to the wide diversity of porphyrins. Porphyrins act as cofactors for a multitude of enzymes that perform a variety of processes within the cell such as methionine synthesis (vitamin B12) or oxygen transport (heme). hydroxymethylbilane = H2O + uroporphyrinogen III Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 3/4. Monomer. Ubiquitous. The disease is caused by variants affecting the gene represented in this entry. Severe congenital erythropoietic porphyria is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders. Belongs to the uroporphyrinogen-III synthase family. Variant Ala-62 was originally reported to result in no detectable enzyme activity (PubMed:1737856), as measured in recombinant crude lysate extracts. Further experiments with the purified enzyme have shown that this variant does not affect activity (PubMed:11689424).