UROD

Chr 1

uroporphyrinogen decarboxylase

Also known as: PCT, UPD

NCBI Gene: 7389 ENSG00000126088 UniProt: P06132

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

DNmechanismLOEUF 1.13

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

60 unique Pathogenic / Likely Pathogenic· 92 VUS of 208 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — UROD

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.73 (0.49–1.13)

0≤0.351.4

Missense OE?0.78 (0.69–0.89)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 15 / 20.5Missense obs/exp: 165 / 210.4Syn Z: 0.73

This gene — mechanism propensity

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

208 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32

Likely Pathogenic28

VUS92

Likely Benign22

Benign5

Conflicting12

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	21	10	1	0	32
Likely Pathogenic	15	12	0	1	28
VUS	0	76	14	2	92
Likely Benign	0	4	11	7	22
Benign	0	0	4	1	5
Conflicting	—				12
Total	36	102	30	11	191

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap UROD — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →