Porphyria cutanea tarda

Summary

Porphyria cutanea tarda (MONDO:0015104) is a disease with 1 cohort gene and 7 clinical trials. Top therapeutic interventions include deferasirox and hydroxychloroquine.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 39
• Clinical trials: 7

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.6	Europe	Validated
Point prevalence	1-9 / 100 000	4	Europe	Validated
Annual incidence	1-9 / 100 000	1	Norway	Validated
Point prevalence	1-5 / 10 000	10	Sweden	Validated

Signs & symptoms

Clinical features (HPO)

39 HPO clinical features (Orphanet curated; top 39 by frequency):

HPO ID	Term	Frequency
HP:0032500	Exacerbated by tobacco use	Very frequent (80-99%)
HP:0000992	Cutaneous photosensitivity	Very frequent (80-99%)
HP:0008066	Abnormal blistering of the skin	Very frequent (80-99%)
HP:0001030	Fragile skin	Very frequent (80-99%)
HP:0010473	Porphyrinuria	Very frequent (80-99%)
HP:0010472	Abnormal circulating porphyrin concentration	Very frequent (80-99%)
HP:0012379	Abnormal enzyme/coenzyme activity	Frequent (30-79%)
HP:0030272	Abnormal erythrocyte enzyme activity	Frequent (30-79%)
HP:0003281	Increased circulating ferritin concentration	Frequent (30-79%)
HP:0012465	Elevated hepatic iron concentration	Frequent (30-79%)
HP:0030955	Alcoholism	Frequent (30-79%)
HP:0200123	Chronic hepatitis	Frequent (30-79%)
HP:0001058	Poor wound healing	Frequent (30-79%)
HP:0012531	Pain	Frequent (30-79%)
HP:0012217	Increased urinary porphobilinogen	Frequent (30-79%)
HP:0003452	Increased serum iron	Frequent (30-79%)
HP:0031876	Decreased hepcidin level	Occasional (5-29%)
HP:0002725	Systemic lupus erythematosus	Occasional (5-29%)
HP:0003774	Stage 5 chronic kidney disease	Occasional (5-29%)
HP:0000819	Diabetes mellitus	Occasional (5-29%)
HP:0001397	Hepatic steatosis	Occasional (5-29%)
HP:0004377	Hematological neoplasm	Occasional (5-29%)
HP:0040189	Scaling skin	Occasional (5-29%)
HP:0005406	Recurrent bacterial skin infections	Occasional (5-29%)
HP:0031292	Cutaneous abscess	Occasional (5-29%)
HP:0000998	Hypertrichosis	Occasional (5-29%)
HP:0001010	Hypopigmentation of the skin	Occasional (5-29%)
HP:0000953	Hyperpigmentation of the skin	Occasional (5-29%)
HP:0001007	Hirsutism	Occasional (5-29%)
HP:0100699	Scarring	Occasional (5-29%)
HP:0000559	Corneal scarring	Occasional (5-29%)
HP:0000656	Ectropion	Occasional (5-29%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Occasional (5-29%)
HP:0001405	Periportal fibrosis	Occasional (5-29%)
HP:0033197	Hepatic lobular inflammation	Occasional (5-29%)
HP:0033196	Portal inflammation	Occasional (5-29%)
HP:0001402	Hepatocellular carcinoma	Occasional (5-29%)
HP:0032999	Increased fecal porphyrin	Occasional (5-29%)
HP:0006562	Viral hepatitis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	porphyria cutanea tarda
Mondo ID	MONDO:0015104
MeSH	D017119
Orphanet	101330
DOID	DOID:3132
ICD-10-CM	E80.1
ICD-11	370983230
NCIT	C27725
SNOMED CT	61860000
UMLS	C0162566
MedGen	56453
GARD	0007433
MedDRA	10036183
Is cancer (heuristic)	no

Also known as: PCT · porphyria cutania tarda

Data availability: 3 ClinVar variants · 6 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › dermatitis › porphyria cutanea tarda

Related subtypes (32): spongiotic dermatitis, atopic eczema, psoriasis, contact dermatitis, urticaria, acneiform dermatitis, acrodermatitis, folliculitis, granuloma annulare, granulomatous dermatitis, lichen planus, neurodermatitis, neurotic excoriation, parapsoriasis, pityriasis rosea, seborrheic dermatitis, acanthosis nigricans, dermatosis papulosa nigra, lichen sclerosus et atrophicus, vitiligo, acne, dermatomyositis, acute generalized exanthematous pustulosis, hydroa vacciniforme, autoimmune bullous skin disease, cutaneous vasculitis, skin infection, intertrigo, lipodermatosclerosis, exfoliative dermatitis, radiodermatitis, food dermatitis

Subtypes (3): sporadic porphyria cutanea tarda, familial porphyria cutanea tarda, hepatoerythropoietic porphyria

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
64678	NM_000374.5(UROD):c.6_15del (p.Glu2fs)	LOC129930433	Pathogenic	no assertion criteria provided
64679	NM_000374.5(UROD):c.346C>T (p.Gln116Ter)	UROD	Pathogenic	criteria provided, multiple submitters, no conflicts
66	NM_000374.5(UROD):c.842G>A (p.Gly281Glu)	UROD	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UROD	Orphanet:443062	Familial porphyria cutanea tarda
UROD	Orphanet:95159	Hepatoerythropoietic porphyria

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
UROD	HGNC:12591	ENSG00000126088	P06132	Uroporphyrinogen decarboxylase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UROD	Uroporphyrinogen decarboxylase	Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UROD	Enzyme (other)	yes	4.1.1.37	Uroporphyrinogen_deCOase, Uroporphyrinogen_deCO2ase_HemE, UROD/MetE-like_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
parotid gland	1
right adrenal gland	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UROD	298	ubiquitous	marker	trabecular bone tissue, parotid gland, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UROD	1,910

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UROD	P06132	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Heme biosynthesis	1	761.3×	0.001	UROD

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
porphyrin-containing compound catabolic process	1	16852.0×	4e-04	UROD
porphyrin-containing compound metabolic process	1	4213.0×	7e-04	UROD
obsolete protoporphyrinogen IX biosynthetic process	1	1685.2×	8e-04	UROD
heme B biosynthetic process	1	1685.2×	8e-04	UROD
heme A biosynthetic process	1	1532.0×	8e-04	UROD
heme biosynthetic process	1	601.9×	0.002	UROD

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Deferasirox	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Hydroxychloroquine.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
UROD	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
UROD	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
UROD	4.1.1.37	uroporphyrinogen decarboxylase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	UROD
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
UROD	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 7.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	3
Not specified	3
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00599326	PHASE3	COMPLETED	Pilot Trial of Deferasirox in the Treatment of Porphyria Cutanea Tarda
NCT01284946	PHASE2	UNKNOWN	Safety and Efficacy of Oral Deferasirox in Patients With Porphyria Cutanea Tarda
NCT01573754	PHASE2	COMPLETED	Hydroxychloroquine and Phlebotomy for Treating Porphyria Cutanea Tarda
NCT03118674	PHASE2	COMPLETED	Harvoni Treatment Porphyria Cutanea Tarda
NCT00005103	Not specified	COMPLETED	Study of the Pathogenesis of Porphyria Cutanea Tarda
NCT00213772	Not specified	COMPLETED	Risk Factors of Porphyria Cutanea Tarda (PCT)
NCT03388944	Not specified	COMPLETED	PCT Guided Stopping of Antibiotic Therapy in Children With Sepsis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DEFERASIROX	4	2
HYDROXYCHLOROQUINE	4	1