UROS

Chr 10AR

uroporphyrinogen III synthase

Also known as: Mgu, UROIIIS

NCBI Gene: 7390ENSG00000188690UniProt: P10746

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]

Primary Disease Associations & Inheritance

Porphyria, congenital erythropoieticMIM #263700
AR
228
ClinVar variants
97
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— UROS
🧬
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.
📋
ClinVar Variants
97 Pathogenic / Likely Pathogenic· 58 VUS of 228 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.73LOEUF
pLI 0.032
Z-score 2.31
OE 0.35 (0.18–0.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.08Z-score
OE missense 1.02 (0.89–1.17)
142 obs / 139.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.35 (0.18–0.73)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.89–1.17)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 5 / 14.5Missense obs/exp: 142 / 139.3Syn Z: 0.32

ClinVar Variant Classifications

228 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic90
Likely Pathogenic7
VUS58
Likely Benign42
Benign26
Conflicting5
90
Pathogenic
7
Likely Pathogenic
58
VUS
42
Likely Benign
26
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
14
73
0
90
Likely Pathogenic
3
2
2
0
7
VUS
0
41
17
0
58
Likely Benign
0
6
18
18
42
Benign
0
1
22
3
26
Conflicting
—5
Total66413221228

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

UROS-related congenital erythropoietic porphyria

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Porphyria, congenital erythropoietic

MIM #263700

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — UROS
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Congenital erythropoietic porphyria.
To-Figueras J et al.·Liver Int
2024Review
Congenital erythropoietic porphyria: Recent advances.
Erwin AL et al.·Mol Genet Metab
2019Review
Urolithins: A Prospective Alternative against Brain Aging.
An L et al.·Nutrients
2023Review
Multi-omic biomarkers associated with multiple sclerosis: from Mendelian randomization to drug prediction.
Yang W et al.·Sci Rep
2025
The uroS and yifB Genes Conserved among Tetrapyrrole Synthesizing-Deficient Bacteroidales Are Involved in Bacteroides fragilis Heme Assimilation and Survival in Experimental Intra-abdominal Infection and Intestinal Colonization.
Parker AC et al.·Infect Immun
2020
Missense UROS mutations causing congenital erythropoietic porphyria reduce UROS homeostasis that can be rescued by proteasome inhibition.
Blouin JM et al.·Hum Mol Genet
2017
Advances in understanding the pathogenesis of congenital erythropoietic porphyria.
Di Pierro E et al.·Br J Haematol
2016Review
HLA-G(∗)01:05N null allele in Mayans (Guatemala) and Uros (Titikaka Lake, Peru): evolution and population genetics.
Arnaiz-Villena A et al.·Hum Immunol
2013
Clinical preferences and treatment attitudes among urologists, gynecologists, and geriatricians: An independent online questionnaire survey for comparison of treatment choices in the management of overactive bladder.
Onur R et al.·Neurourol Urodyn
2022
Bioactive release and modulation of urolithin metabotype A phenotype gut microbiota during in vitro digestion and fermentation of ellagic acid-rich fruit polyphenols.
Xie Z et al.·Food Funct
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools