Research panel - Severe Paediatric Disorders
Gene: CPOX

CPOX (coproporphyrinogen oxidase)
EnsemblGeneIds (GRCh38): ENSG00000080819
EnsemblGeneIds (GRCh37): ENSG00000080819
OMIM: 612732, Gene2Phenotype
CPOX is in 10 panels

2 reviews

Sharon Whatley (International Porphyria Network)

Green List (high evidence)

Relevant metabolic investigation: Urine porphobilinogen, plasma porphyrin fluorescence emission and faecal coproporphyrin isomer (III:I) ratio (for hereditary coproporphyria) and faecal harderoporphyrin (for harderoporphyria)

PMID: 23236641 Wang reports that autosomal dominant, hereditary coproporphyria (HCP) is classified as both an acute (hepatic) porphyria (with abdominal, cardiovascular and neurologic symptoms) and a chronic (cutaneous) porphyria with long-standing photosensitivity. It usually becomes symptomatic in early adulthood.

However, eight paediatric patients (from five families) with biallelic pathogenic variants had neonatal jaundice, haemolytic anaemia and splenomegaly or hepatosplenomegaly (PMID: 40296768 Kelestemur, 30828546 Moghe, 21103937 Hasanoglu, 9454777 Lamoril, 7757079 Lamoril). Of this eight, 5 patients (from 3 families) had at least one pathogenic variant located in the presumed CPOX active site (Asp400–Lys404) and harderoporphyrin in their faecal samples leading to a diagnosis of harderoporphyria (PMID: 30828546 Moghe, 9454777 Lamoril, 7757079 Lamoril). In three patients (two families) the variants were outside this region. These homozygous hereditary coproporphyria patients were not tested for faecal harderoporphyrin (40296768 Kelestemur, 21103937 Hasanoglu).

PMID: 21103937 Hasanoglu and 6886003 Nordmann reported patients with severe cutaneous photosensitivity and skin fragility especially when exposed to phototherapy for neonatal jaundice.

PMID: 30828546 Moghe reports that in most cases, severe manifestations improve after early childhood and are compatible with prolonged survival.

PMID: 21103937 Hasanoglu has reported the only case of an early death in a patient with homozygous hereditary coproporphyria at 5 months due to a condition resembling an acute porphyria attack.

PMID: 74745 Grandchamp reported a child with homozygous HCP who presented at 10 years with an acute porphyria attack associated with a severe hyponatraemia.

PMID: 28349448 Hasegawa and 11739202 Takeuchi reported patients with neonatal onset hereditary coproporphyria. Both suffered photosensitivity of the skin following phototherapy, haemolytic anaemia, jaundice, adrenocortical insufficiency and a disorder of sexual development. Only one heterozygous pathogenic variant was identified in each patient.

Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the CPOX gene, due to its low clinical penetrance (~0.4%).
Created: 11 Sep 2025, 11:02 a.m. | Last Modified: 11 Sep 2025, 11:02 a.m.

Panel Version: 1.213

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
121300; 618892

Publications

Created: 11 Sep 2025, 11:02 a.m.
Last Modified: 11 Sep 2025, 11:02 a.m.
Panel version: 1.213

Louise Daugherty (Genomics England Curator)

I don't know

Initial gene list (NGC_genelist-20190823_GREEN_dis_moi_forCuration_20200211.xlsx) collated by Dr Courtney French (University of Cambridge University Hospital NHS Foundation), Dr Karyn Megy (Clinical Feedback Lead, NIHR BioResource - Rare Diseases Study, University of Cambridge University Hospital NHS Foundation), Dr Alba Sanchis-Juan (NIHR BioResource - Rare Diseases Study, University of Cambridge University Hospital NHS Foundation) and Lucy Raymond (Professor of Medical Genetics and Neurodevelopment, University of Cambridge University Hospital NHS Foundation). Submitted to the PanelApp resource January 2020 on behalf of the Next Generation Children Project, Addenbrookes' Hospital, Cambridge. Gene Symbol submitted: CPOX; Recommended initial gene rating: Green List (high evidence); Phenotypes: Coproporphyria, 121300 (3) | Harderoporphyria, 121300 (3); Mode of inheritance: Autosomal dominant | Autosomal dominant
Created: 20 Feb 2020, 5:17 p.m. | Last Modified: 20 Feb 2020, 5:17 p.m.

Panel Version: 0.12

Created: 20 Feb 2020, 5:17 p.m.
Last Modified: 20 Feb 2020, 5:17 p.m.
Panel version: 0.12

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Next Generation Children Project
Expert Review Green
Expert list

Phenotypes

Harderoporphyria, 121300
Coproporphyria, 121300

OMIM

612732

Clinvar variants

Variants in CPOX

Penetrance

None

Publications

30847515

Panels with this gene