UROD

Chr 1ADAR

uroporphyrinogen decarboxylase

Also known as: PCT, UPD

NCBI Gene: 7389ENSG00000126088UniProt: P06132OMIM: 613521

This gene encodes uroporphyrinogen decarboxylase, which catalyzes the sequential decarboxylation of four acetate side chains of uroporphyrinogen to form coproporphyrinogen in the heme biosynthetic pathway. Mutations cause porphyria cutanea tarda and hepatoerythropoietic porphyria, conditions affecting the skin and liver that can manifest with photosensitivity and hepatic dysfunction. The gene shows both autosomal dominant and autosomal recessive inheritance patterns depending on the specific condition.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismAD/ARLOEUF 1.132 OMIM phenotypes
Clinical Summary— UROD
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Gene-Disease Validity (ClinGen)
UROD-related inherited porphyria · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
65 unique Pathogenic / Likely Pathogenic· 102 VUS of 223 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — UROD
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
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
1.11Z-score
OE missense 0.78 (0.69–0.89)
165 obs / 210.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.73 (0.49–1.13)
0≤0.351.4
Missense OE0.78 (0.69–0.89)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 15 / 20.5Missense obs/exp: 165 / 210.4Syn Z: 0.73
DN
0.6939th %ile
GOF
0.5465th %ile
LOF
0.2678th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

223 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
21
10
5
0
36
Likely Pathogenic
14
12
2
1
29
VUS
0
76
24
2
102
Likely Benign
0
4
11
7
22
Benign
0
0
4
1
5
Conflicting
—12
Total351024611206

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
[Porphyria cutanea tarda].
Mistegård J et al.·Ugeskr Laeger
2025Review
Association between hepatitis C virus and porphyria cutanea tarda.
To-Figueras J·Mol Genet Metab
2019Review
Porphyria cutanea tarda: a unique iron-related disorder.
Leaf RK et al.·Hematology Am Soc Hematol Educ Program
2024Review
Porphyria cutanea tarda: Recent update.
Singal AK·Mol Genet Metab
2019Review
Murine models of the human porphyrias: Contributions toward understanding disease pathogenesis and the development of new therapies.
Yasuda M et al.·Mol Genet Metab
2019Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients