UROD-related inherited porphyria

Summary

UROD-related inherited porphyria (MONDO:0100498) is a disease caused by UROD (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: UROD (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	UROD-related inherited porphyria
Mondo ID	MONDO:0100498
GARD	0026251
Is cancer (heuristic)	no

Also known as: UROD-related porphyria

Data availability: 2 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary skin disorder › hereditary photodermatosis › inherited porphyria › UROD-related inherited porphyria

Related subtypes (8): erythropoietic protoporphyria, cutaneous porphyria, porphyria due to ALA dehydratase deficiency, erythropoietic uroporphyria associated with myeloid malignancy, chester porphyria, HMBS-related hepatic porphyria, PPOX-related hepatic porphyria, CPOX-related hereditary coproporphyria

Subtypes (2): 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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1457336	NM_000374.5(UROD):c.616C>T (p.Gln206Ter)	UROD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3061020	NM_000374.5(UROD):c.21-10T>A	UROD	Uncertain significance	criteria provided, single submitter

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.