Cutaneous photosensitivity with a likely genetic cause

Gene: CPOX

Comment on phenotypes: OMIM phenotypes accessed on 20th October 2025

Created: 21 Oct 2025, 10:46 a.m. | Last Modified: 21 Oct 2025, 10:46 a.m.

Panel Version: 3.13

Green List (high evidence)

Comment on mode of inheritance: As reviewed by Sharon Whatley, variants in CPOX may cause autosomal dominant or autosomal recessive porphyria. Monoallelic variants in CPOX have very low clinical penetrance (<1%) and may be challenging to report as diagnostic. Hence, BIALLELIC, autosomal or pseudoautosomal MOI would be more appropriate. This gene has been tagged for MOI Expert Review. CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 20th Oct 2025).

Created: 20 Oct 2025, 2:24 p.m. | Last Modified: 4 Nov 2025, 1:44 p.m.

Panel Version: 3.13

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Coproporphyria, OMIM:121300; Harderoporphyria, OMIM:618892

Publications

• 6886003
• 7757079
• 8012360
• 9454777
• 10505225
• 11074238
• 16159891
• 21103937
• 23236641
• 30828546
• 33008663
• 40296768

Green List (high evidence)

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

PMID: 23236641 Wang reports that 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. Clinical penetrance is low, and symptoms are very rare before puberty. The cutaneous findings in HCP resemble those in porphyria cutanea tarda (PCT) and in variegate porphyria (VP).
PMID: 11074238 Kuhnel reports that bullae and fragility of light-exposed skin occurred in only 14% of 46 patients with HCP (current or past).
There have been 12 patients from 9 families reported with clinical details and biallelic pathogenic variants (PMID: 40296768 Kelestemur, 33008663 Fukui, 30828546 Moghe, 21103937 Hasanoglu, 16159891 Schmitt, 10505225 Doss, 9454777 Lamoril, 7757079 Lamoril, 8012360 Martasek). 10 of these 12 individuals had cutaneous symptoms. The most common manifestation was pigmentation (5 patients, 2 of these had adrenal insufficiency) followed by blisters (3), skin fragility (3), erythema (2), other symptoms scarring, papules, milia and hypertrichosis were reported in single patients. Two patients had severe cutaneous photosensitivity following phototherapy (PMID: 6886003 Nordmann, 21103937 Hasanoglu).
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, 9:54 a.m. | Last Modified: 11 Sep 2025, 9:54 a.m.

Panel Version: 3.9

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

Phenotypes
121300; 618892

Publications

• 23236641
• 11074238
• 40296768
• 33008663
• 30828546
• 21103937
• 16159891
• 10505225
• 9454777
• 7757079
• 8012360
• 6886003

Green List (high evidence)

Following discussion with the Genomics England clinical team it was agreed that genes associated with porphyrias should be included on this panel. Therefore added to panel as a Green gene.

Created: 2 Dec 2019, 3:48 p.m. | Last Modified: 2 Dec 2019, 3:48 p.m.

Panel Version: 0.10