Hepatoerythropoietic porphyria

Summary

Hepatoerythropoietic porphyria (MONDO:0019799) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 5
• Phenotypes (HPO): 37

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		40	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

37 HPO clinical features (Orphanet curated; top 37 by frequency):

HPO ID	Term	Frequency
HP:0012379	Abnormal enzyme/coenzyme activity	Very frequent (80-99%)
HP:0007537	Severe 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:0040318	Red urine	Frequent (30-79%)
HP:0010472	Abnormal circulating porphyrin concentration	Frequent (30-79%)
HP:0032999	Increased fecal porphyrin	Frequent (30-79%)
HP:0040320	Red-brown urine	Frequent (30-79%)
HP:0100699	Scarring	Frequent (30-79%)
HP:0030756	Erythrodontia	Frequent (30-79%)
HP:0001790	Nonimmune hydrops fetalis	Frequent (30-79%)
HP:0000953	Hyperpigmentation of the skin	Frequent (30-79%)
HP:0001010	Hypopigmentation of the skin	Frequent (30-79%)
HP:0040322	Purple urine	Frequent (30-79%)
HP:0200041	Skin erosion	Frequent (30-79%)
HP:0005406	Recurrent bacterial skin infections	Frequent (30-79%)
HP:0001878	Hemolytic anemia	Occasional (5-29%)
HP:0012804	Corneal ulceration	Occasional (5-29%)
HP:0001072	Thickened skin	Occasional (5-29%)
HP:0002219	Facial hypertrichosis	Occasional (5-29%)
HP:0001744	Splenomegaly	Occasional (5-29%)
HP:0001892	Abnormal bleeding	Occasional (5-29%)
HP:0000656	Ectropion	Occasional (5-29%)
HP:0000938	Osteopenia	Occasional (5-29%)
HP:0001560	Abnormality of the amniotic fluid	Occasional (5-29%)
HP:0011457	Loss of eyelashes	Occasional (5-29%)
HP:0004552	Scarring alopecia of scalp	Occasional (5-29%)
HP:0000939	Osteoporosis	Occasional (5-29%)
HP:0012132	Erythroid hyperplasia	Occasional (5-29%)
HP:0003401	Paresthesia	Very rare (<1-4%)
HP:0000989	Pruritus	Very rare (<1-4%)
HP:0000969	Edema	Very rare (<1-4%)
HP:0000618	Blindness	Very rare (<1-4%)
HP:0100532	Scleritis	Very rare (<1-4%)
HP:0500046	Seborrhoeic blepharitis	Very rare (<1-4%)
HP:0001096	Keratoconjunctivitis	Very rare (<1-4%)
HP:0002797	Osteolysis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hepatoerythropoietic porphyria
Mondo ID	MONDO:0019799
MeSH	D017121
Orphanet	95159
DOID	DOID:5230
ICD-11	214080046
NCIT	C84754
SNOMED CT	111386004
UMLS	C0162569
MedGen	57940
GARD	0006169
Is cancer (heuristic)	no

Also known as: HEP

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record · 6 cell lines.

Disease family

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

Related subtypes (2): sporadic porphyria cutanea tarda, familial porphyria cutanea tarda

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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
66	NM_000374.5(UROD):c.842G>A (p.Gly281Glu)	UROD	Pathogenic	criteria provided, single submitter
69	NM_000374.5(UROD):c.874C>G (p.Arg292Gly)	UROD	Pathogenic	no assertion criteria provided
70	NM_000374.5(UROD):c.185C>T (p.Pro62Leu)	UROD	Pathogenic	criteria provided, single submitter
71	NM_000374.5(UROD):c.932A>G (p.Tyr311Cys)	UROD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
68	NM_000374.5(UROD):c.499G>A (p.Glu167Lys)	UROD	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
UROD	Definitive	Semidominant	UROD-related inherited porphyria	8

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	gencc,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

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: 0.