UROD

Chr 1ADAR

uroporphyrinogen decarboxylase

Also known as: PCT, UPD

NCBI Gene: 7389ENSG00000126088UniProt: P06132

This gene encodes an enzyme in the heme biosynthetic pathway. This enzyme is responsible for catalyzing the conversion of uroporphyrinogen to coproporphyrinogen through the removal of four carboxymethyl side chains. Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoetic porphyria.[provided by RefSeq, Aug 2010]

Primary Disease Associations & Inheritance

Porphyria cutanea tardaMIM #176100
ADAR
Porphyria, hepatoerythropoieticMIM #176100
ADAR
UniProtFamilial porphyria cutanea tarda
206
ClinVar variants
65
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— UROD
🧬
Gene-Disease Validity (ClinGen)
UROD-related inherited porphyria · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 102 VUS of 206 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.
1.13LOEUF
pLI 0.000
Z-score 1.13
OE 0.73 (0.49–1.13)
Tolerant

Highly tolerant — LoF variants common in population

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.
1.11Z-score
OE missense 0.78 (0.69–0.89)
165 obs / 210.4 exp
Tolerant

Mild missense constraint

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.0.73 (0.49–1.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.69–0.89)
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.0.89
0≤1.21.6
LoF obs/exp: 15 / 20.5Missense obs/exp: 165 / 210.4Syn Z: 0.73

ClinVar Variant Classifications

206 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic29
VUS102
Likely Benign22
Benign5
Conflicting12
36
Pathogenic
29
Likely Pathogenic
102
VUS
22
Likely Benign
5
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
10
15
0
36
Likely Pathogenic
10
11
7
1
29
VUS
0
75
25
2
102
Likely Benign
0
4
11
7
22
Benign
0
0
4
1
5
Conflicting
—12
Total211006211206

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

View in ClinVar →

Protein Context — Lollipop Plot

UROD · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Porphyria cutanea tarda

MIM #176100

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Porphyria, hepatoerythropoietic

MIM #176100

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
📖
GeneReview available — UROD
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Porphyria cutanea tarda: a unique iron-related disorder.
Leaf RK et al.·Hematology Am Soc Hematol Educ Program
2024Review
[Porphyria cutanea tarda].
Mistegård J et al.·Ugeskr Laeger
2025Review
Porphyria cutanea tarda.
Elder GH·Semin Liver Dis
1998Review
Porphyria cutanea tarda: Recent update.
Singal AK·Mol Genet Metab
2019Review
Computational identification of pathogenic associated nsSNPs and its structural impact in UROD gene: a molecular dynamics approach.
Doss CG et al.·Cell Biochem Biophys
2014
Association between hepatitis C virus and porphyria cutanea tarda.
To-Figueras J·Mol Genet Metab
2019Review
Porphyria cutanea tarda--when skin meets liver.
Frank J et al.·Best Pract Res Clin Gastroenterol
2010Review
Porphyria cutanea tarda.
Fritsch C et al.·Skin Pharmacol Appl Skin Physiol
1998Review
Familial porphyria cutanea tarda in Spain: characterization of eight novel mutations in the UROD gene and haplotype analysis of the common p.G281E mutation.
Gómez-Abecia S et al.·Gene
2013
Familial and sporadic porphyria cutanea tarda: characterization and diagnostic strategies.
Aarsand AK et al.·Clin Chem
2009
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