PPOX

Chr 1

protoporphyrinogen oxidase

Also known as: PPO, V290M, VP, VPCO

This gene encodes the penultimate enzyme of heme biosynthesis, which catalyzes the 6-electron oxidation of protoporphyrinogen IX to form protoporphyrin IX. Mutations in this gene cause variegate porphyria, an autosomal dominant disorder of heme metabolism resulting from a deficiency in protoporphyrinogen oxidase, an enzyme located on the inner mitochondrial membrane. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtVariegate porphyria
UniProtVariegate porphyria, childhood-onset

Clinical highlights

Gene-disease validity (ClinGen)
variegate porphyria · SDStrongappropriate for clinical testing
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
3
Active trials
21
Pubs (1 yr)
P/LP submissions
P/LP missense
0.57
LOEUF
DN
Mechanism· predicted
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GeneReview available — PPOX
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

Moderate LoF intolerance
LoF Constraint?
0.57LOEUF
pLI 0.028
Z-score 3.09
OE 0.30 (0.170.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.98Z-score
OE missense 0.83 (0.740.93)
216 obs / 260.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.30 (0.170.57)
00.351.4
Missense OE?0.83 (0.740.93)
00.61.4
Synonymous OE?1.05
01.21.6
LoF obs/exp: 7 / 23.0Missense obs/exp: 216 / 260.3Syn Z: -0.43

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PPOX · protein map & ClinVar variants

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