UROS

Chr 10AR

uroporphyrinogen III synthase

Also known as: Mgu, UROIIIS

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.731 OMIM phenotype
Clinical SummaryUROS
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Gene-Disease Validity (ClinGen)
cutaneous porphyria · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.73LOEUF
pLI 0.032
Z-score 2.31
OE 0.35 (0.180.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.08Z-score
OE missense 1.02 (0.891.17)
142 obs / 139.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.35 (0.180.73)
00.351.4
Missense OE1.02 (0.891.17)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 5 / 14.5Missense obs/exp: 142 / 139.3Syn Z: 0.32
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveUROS-related congenital erythropoietic porphyriaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.73top 25%
GOF
0.4678th %ile
LOF
0.2289th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

UROS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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