CPOX

Chr 3ADAR

coproporphyrinogen oxidase

Also known as: COX, CPO, CPX, HARPO, HCP

NCBI Gene: 1371 ENSG00000080819 UniProt: P36551 OMIM: 612732

The enzyme catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX as the sixth step in heme biosynthesis and is located in the mitochondrial intermembrane space. Mutations cause coproporphyria and harderoporphyria, which are acute hepatic porphyrias that can present with neurological crises, abdominal pain, and psychiatric symptoms. The gene shows both autosomal dominant and autosomal recessive inheritance patterns depending on the specific variant and resulting phenotype severity.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is the sixth enzyme of the heme biosynthetic pathway. The encoded enzyme is soluble and found in the intermembrane space of mitochondria. This enzyme catalyzes the stepwise oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX, a precursor of heme. Defects in this gene are a cause of hereditary coproporphyria (HCP).[provided by RefSeq, Oct 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

AD/ARLOEUF 0.542 OMIM phenotypes

Clinical Summary— CPOX

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Gene-Disease Validity (ClinGen)

CPOX-related hereditary coproporphyria · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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ClinVar Variants

43 unique Pathogenic / Likely Pathogenic· 176 VUS of 348 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CPOX

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.54LOEUF

pLI 0.172

Z-score 3.03

OE 0.26 (0.13–0.54)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.35Z-score

OE missense 0.75 (0.66–0.85)

173 obs / 230.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.13–0.54)

0≤0.351.4

Missense OE?0.75 (0.66–0.85)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 5 / 19.4Missense obs/exp: 173 / 230.6Syn Z: -0.58

ClinVar Variant Classifications

348 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30

Likely Pathogenic13

VUS176

Likely Benign61

Benign42

Conflicting15

Pathogenic

Likely Pathogenic

176

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	22	7	1	0	30
Likely Pathogenic	10	3	0	0	13
VUS	1	142	28	5	176
Likely Benign	0	3	17	41	61
Benign	0	7	30	5	42
Conflicting	—				15
Total	33	162	76	51	337

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap CPOX — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →