UROS

Chr 10AR

uroporphyrinogen III synthase

Also known as: Mgu, UROIIIS

NCBI Gene: 7390 ENSG00000188690 UniProt: P10746 OMIM: 606938

The encoded protein catalyzes the cyclization of hydroxymethylbilane to uroporphyrinogen III, a critical step in heme biosynthesis that serves as the branch point for porphyrin synthesis pathways. Mutations cause congenital erythropoietic porphyria (Gunther's disease), which follows autosomal recessive inheritance and typically presents in early infancy with severe photosensitivity, hemolytic anemia, and cutaneous manifestations. The gene shows relatively low constraint to loss-of-function variation (pLI = 0.03, LOEUF = 0.73), consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene catalyzes the fourth step of porphyrin biosynthesis in the heme biosynthetic pathway. Defects in this gene cause congenital erythropoietic porphyria (Gunther's disease). [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Porphyria, congenital erythropoieticMIM #263700

Clinical highlights

Gene-disease validity (ClinGen)

cutaneous porphyria · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.73

LOEUF

LOF

Mechanism· G2P