UROD

Summary

UROD (uroporphyrinogen decarboxylase, HGNC:12591) is a protein-coding gene on chromosome 1p34.1, encoding Uroporphyrinogen decarboxylase (P06132). 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. It is a selective cancer dependency (DepMap: 56.3% of cell lines).

This gene encodes an enzyme in the heme biosynthetic pathway. This enzyme is responsible for catalyzing the conversion of uroporphyrinogen to coproporphyrinogen through the removal of four carboxymethyl side chains. Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoetic porphyria.

Source: NCBI Gene 7389 — RefSeq curated summary.

At a glance

• Gene–disease (curated): UROD-related inherited porphyria (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 202 total — 28 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 48
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 56.3% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency emerging evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000374

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12591
Approved symbol	UROD
Name	uroporphyrinogen decarboxylase
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000126088
Ensembl biotype	protein_coding
OMIM	613521
Entrez	7389

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 30 protein_coding, 11 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000246337, ENST00000428106, ENST00000434478, ENST00000460334, ENST00000460906, ENST00000461035, ENST00000462688, ENST00000463092, ENST00000465678, ENST00000466193, ENST00000469548, ENST00000472254, ENST00000473012, ENST00000478467, ENST00000486699, ENST00000490385, ENST00000491300, ENST00000491773, ENST00000494399, ENST00000496439, ENST00000636293, ENST00000636836, ENST00000650713, ENST00000651476, ENST00000652165, ENST00000652287, ENST00000652514, ENST00000894914, ENST00000894915, ENST00000894916, ENST00000894917, ENST00000894918, ENST00000894919, ENST00000894920, ENST00000894921, ENST00000936999, ENST00000937000, ENST00000937001, ENST00000937002, ENST00000937003, ENST00000937004, ENST00000937005, ENST00000937006, ENST00000937007, ENST00000937008, ENST00000962747

RefSeq mRNA: 1 — MANE Select: NM_000374 NM_000374

CCDS: CCDS518

Canonical transcript exons

ENST00000246337 — 10 exons

Exon	Start	End
ENSE00001901830	45012254	45012285
ENSE00003495209	45014736	45014836
ENSE00003540094	45013909	45014070
ENSE00003545324	45013136	45013215
ENSE00003552933	45014439	45014576
ENSE00003573698	45013292	45013354
ENSE00003591712	45013594	45013791
ENSE00003628717	45014940	45015006
ENSE00003672572	45012907	45013019
ENSE00003684657	45015337	45015575

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 79.7544 / max 2492.2248, expressed in 1827 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2661	64.8455	1826
2667	3.7574	463
2666	3.6517	212
2660	3.0214	1500
2659	2.1556	1365
2662	1.3531	708
2665	0.6961	78
2663	0.2164	48
2664	0.0571	16

Top tissues by expression

299 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.47	gold quality
parotid gland	UBERON:0001831	99.33	gold quality
right adrenal gland	UBERON:0001233	98.70	gold quality
right adrenal gland cortex	UBERON:0035827	98.66	gold quality
parietal pleura	UBERON:0002400	98.51	gold quality
left adrenal gland	UBERON:0001234	98.49	gold quality
left adrenal gland cortex	UBERON:0035825	98.49	gold quality
adrenal cortex	UBERON:0001235	98.37	gold quality
endothelial cell	CL:0000115	98.33	gold quality
adrenal gland	UBERON:0002369	97.95	gold quality
pleura	UBERON:0000977	97.88	gold quality
middle temporal gyrus	UBERON:0002771	97.79	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.69	gold quality
bone marrow	UBERON:0002371	97.64	gold quality
apex of heart	UBERON:0002098	97.52	gold quality
pancreatic ductal cell	CL:0002079	97.51	gold quality
germinal epithelium of ovary	UBERON:0001304	97.46	gold quality
visceral pleura	UBERON:0002401	97.35	gold quality
stromal cell of endometrium	CL:0002255	97.22	gold quality
right lobe of liver	UBERON:0001114	97.11	gold quality
pigmented layer of retina	UBERON:0001782	96.88	gold quality
retina	UBERON:0000966	96.85	gold quality
bone marrow cell	CL:0002092	96.83	gold quality
cervix squamous epithelium	UBERON:0006922	96.82	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.75	gold quality
nephron tubule	UBERON:0001231	96.73	gold quality
lower esophagus	UBERON:0013473	96.73	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.61	gold quality
right lobe of thyroid gland	UBERON:0001119	96.60	gold quality
left lobe of thyroid gland	UBERON:0001120	96.58	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	1981.84
E-GEOD-130473	yes	1452.04
E-MTAB-10042	yes	834.16
E-CURD-112	yes	630.17
E-HCAD-4	yes	413.65
E-HCAD-6	yes	67.44
E-CURD-122	yes	21.96
E-MTAB-9067	yes	20.18
E-HCAD-9	yes	8.03
E-CURD-98	no	1573.08
E-ANND-5	no	608.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, PPARA

miRNA regulators (miRDB)

22 targeting UROD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-676-3P	97.86	65.70	668
HSA-MIR-6718-5P	97.24	68.15	553
HSA-MIR-2355-3P	96.84	68.54	909
HSA-MIR-3976	96.67	67.79	1187
HSA-MIR-1226-5P	96.50	65.28	643
HSA-MIR-6834-5P	96.25	64.88	823
HSA-MIR-6734-5P	95.70	65.56	950
HSA-MIR-3679-5P	94.75	66.46	862
HSA-MIR-1185-5P	94.47	65.95	725

Functional genomics

ClinGen dosage: haploinsufficiency 2 (emerging evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 56.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• Sequence deletions in uroporphyrinogen decarboxylase is associated with Porphyria Cutanea Tarda. (PMID:15046048)
• we identified eight mutations in 18 previously unclassified porphyria cutanea tarda families (PMID:15186324)
• Sequencing of the hydroxymethylbilane synthase and uroporphyrinogen decarboxylase genes confirmed the relatively rare diagnosis of dual porphyria, and revealed a novel uroporphyrinogen decarboxylase mutation (PMID:16390615)
• There is a high degree of molecular heterogeneity of familial porphyria cutanea tarda in Spain and molecular genetic analysis is useful in distinguish between F-PCT and sporadic PCT. (PMID:17627795)
• role of UROD mutations as a strong risk factor for porphyria cutanea tarda even in areas where environmental factors (hepatitis C virus) have been shown to be highly associated with the disease (PMID:19419417)
• Expression of the D306Y mutation results in an insoluble recombinant protein. G318R and K297N have little effect on the structure or activity of recombinant URO-D, but the proteins display reduced stability in vitro. (PMID:19656450)
• description of 3 siblings with hepatoerythropoietic porphyria; sequencing of the UROD gene revealed compound heterozygosity for a novel missense mutation, V166A, and a complex deletion/insertion, 645del1053ins10 (PMID:20479301)
• function of Arg37 in uroporphyrinogen III decarboxylase (PMID:20553007)
• Hepatoerythropoietic porphyria and familial porphyria cutanea tarda G281E mutation in the uroporphyrinogen decarboxylase gene (PMID:21079081)
• Mutations in UROD gene is associated with familial porphyria cutanea tarda. (PMID:22382040)
• Data suggest that the traditional Chinese medicine (TCM) candidate potential three-in-one inhibitors for three drug target proteins epidermal growth factor receptor (EGFR), Her2, and uroporphyrinogen decarboxylase (UROD) against head and neck cancer. (PMID:23140436)
• analysis of uroporphyrinogen decarboxylase as a potential target for specific components of traditional Chinese medicine (PMID:23209648)
• Among seventeen F-PCT patients, sixteen UROD mutations were identified. (PMID:23545314)
• a new insight in the conformational changes occurred in the mutant structures of UROD protein. (PMID:24777812)
• a new mutation in the UROD gene in Egyptian patients with Hepatoerythropoietic porphyria, is reported. (PMID:26789143)
• These results expand the molecular heterogeneity of Porphyria Cutanea Tarda and Hepatoerythropoietic Porphyria by adding a total of 19 novel UROD mutations. (PMID:30514647)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	urod	ENSDARG00000006818
mus_musculus	Urod	ENSMUSG00000028684
rattus_norvegicus	Urod	ENSRNOG00000018211
drosophila_melanogaster	Urod	FBGN0033428

Paralogs (4): MTR (ENSG00000116984), BHMT2 (ENSG00000132840), BHMT (ENSG00000145692), MTHFR (ENSG00000177000)

Protein

Protein identifiers

Uroporphyrinogen decarboxylase — P06132 (reviewed: P06132)

All UniProt accessions (14): P06132, A0A1B0GVN9, A0A1B0GVZ4, A0A494BZV1, A0A494BZY8, A0A494C007, A0A494C085, A0A494C0P4, A0A494C0Q8, A0A494C0S8, A0A494C1D8, A0A494C1T3, H0Y5R6, Q5T446

UniProt curated annotations — full annotation on UniProt →

Function. 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. Isomer I or isomer III of uroporphyrinogen may serve as substrate, but only coproporphyrinogen III can ultimately be converted to heme. In vitro also decarboxylates pentacarboxylate porphyrinogen I.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol.

Disease relevance. Familial porphyria cutanea tarda (FPCT) [MIM:176100] A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Familial porphyria cutanea tarda is an autosomal dominant disorder characterized by light-sensitive dermatitis, with onset in later life. It is associated with the excretion of large amounts of uroporphyrin in the urine. Iron overload is often present in association with varying degrees of liver damage. The disease is caused by variants affecting the gene represented in this entry. Hepatoerythropoietic porphyria (HEP) [MIM:176100] A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. HEP is a cutaneous porphyria that presents in infancy. It is characterized biochemically by excessive excretion of acetate-substituted porphyrins and accumulation of protoporphyrin in erythrocytes. Uroporphyrinogen decarboxylase levels are very low in erythrocytes and cultured skin fibroblasts. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 4/4.

Similarity. Belongs to the uroporphyrinogen decarboxylase family.

RefSeq proteins (1): NP_000365* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000257	Uroporphyrinogen_deCOase	Domain
IPR006361	Uroporphyrinogen_deCO2ase_HemE	Family
IPR038071	UROD/MetE-like_sf	Homologous_superfamily

Pfam: PF01208

Enzyme classification (BRENDA):

• EC 4.1.1.37 — uroporphyrinogen decarboxylase (BRENDA: 18 organisms, 45 substrates, 83 inhibitors, 54 Km, 7 kcat entries)

Substrate kinetics (BRENDA)

15 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UROPORPHYRINOGEN I	—	10
UROPORPHYRINOGEN III	—	9
5-COOH-PORPHYRINOGEN I	0.0001–0.0022	6
7-COOH-PORPHYRINOGEN	0.0002–0.0013	4
5-COOH-PORPHYRINOGEN III	0.0001–0.0004	3
6-COOH-PORPHYRINOGEN I	0.0003–0.0029	3
7-COOH-PORPHYRINOGEN I	—	3
UROPORPHYRINOGEN-I	0.0277–0.0381	3
UROPORPHYRINOGEN-III	0.0108–0.0148	3
8-CARBOXYLPORPHYRINOGEN	0.0015–0.0105	2
8-COOH-PORPHYRINOGEN III	0.0003–0.0005	2
6-COOH-PORPHYRINOGEN III	0.0006	1
7-COOH, PORPHYRINOGEN	0.0023	1
7-COOH-PORPHYRINOGEN III	0.0003	1
8-COOH-PORPHYRINOGEN I	0.0008	1

Catalyzed reactions (Rhea), 2 shown:

• uroporphyrinogen III + 4 H(+) = coproporphyrinogen III + 4 CO2 (RHEA:19865)
• uroporphyrinogen I + 4 H(+) = coproporphyrinogen I + 4 CO2 (RHEA:31239)

UniProt features (98 total): sequence variant 41, helix 21, binding site 15, strand 9, mutagenesis site 4, sequence conflict 3, turn 2, chain 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
1R3S	X-RAY DIFFRACTION	1.65
1R3Q	X-RAY DIFFRACTION	1.7
1R3T	X-RAY DIFFRACTION	1.7
1R3W	X-RAY DIFFRACTION	1.7
3GW3	X-RAY DIFFRACTION	1.7
1R3Y	X-RAY DIFFRACTION	1.75
1URO	X-RAY DIFFRACTION	1.8
1R3R	X-RAY DIFFRACTION	1.85
1R3V	X-RAY DIFFRACTION	1.9
2Q71	X-RAY DIFFRACTION	1.9
2Q6Z	X-RAY DIFFRACTION	2
3GW0	X-RAY DIFFRACTION	2
1JPH	X-RAY DIFFRACTION	2.1
3GVQ	X-RAY DIFFRACTION	2.1
1JPK	X-RAY DIFFRACTION	2.2
3GVR	X-RAY DIFFRACTION	2.2
1JPI	X-RAY DIFFRACTION	2.3
3GVV	X-RAY DIFFRACTION	2.8
3GVW	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06132-F1	96.90	0.94

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 86 (transition state stabilizer)

Ligand- & substrate-binding residues (15): 37; 164; 164; 219; 219; 339; 339; 37; 39; 39; 41; 41 …

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (4):

Position	Phenotype
86	5-10% of wild-type activity.
86	very low activity. binds substrate with similar geometry as wild-type.
86	no activity. unable to bind substrate.
164	25-30% of wild-type activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-189451	Heme biosynthesis

MSigDB gene sets: 283 (showing top): GNF2_PRDX2, REACTOME_METABOLISM_OF_PORPHYRINS, DITTMER_PTHLH_TARGETS_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_TETRAPYRROLE_BIOSYNTHETIC_PROCESS, GCM_MYCL1, GNF2_ANK1, GOBP_PORPHYRIN_CONTAINING_COMPOUND_METABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, chr1p34, GOBP_TETRAPYRROLE_METABOLIC_PROCESS, GOBP_PIGMENT_METABOLIC_PROCESS, GNF2_SPTA1

GO Biological Process (8): porphyrin-containing compound metabolic process (GO:0006778), obsolete protoporphyrinogen IX biosynthetic process (GO:0006782), heme biosynthetic process (GO:0006783), heme A biosynthetic process (GO:0006784), heme B biosynthetic process (GO:0006785), porphyrin-containing compound catabolic process (GO:0006787), porphyrin-containing compound biosynthetic process (GO:0006779), heme metabolic process (GO:0042168)

GO Molecular Function (4): uroporphyrinogen decarboxylase activity (GO:0004853), protein binding (GO:0005515), lyase activity (GO:0016829), carboxy-lyase activity (GO:0016831)

GO Cellular Component (3): nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of porphyrins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
porphyrin-containing compound metabolic process	3
cellular anatomical structure	3
heme biosynthetic process	2
tetrapyrrole metabolic process	1
porphyrin-containing compound biosynthetic process	1
heme metabolic process	1
pigment biosynthetic process	1
tetrapyrrole catabolic process	1
tetrapyrrole biosynthetic process	1
pigment metabolic process	1
carboxy-lyase activity	1
binding	1
catalytic activity	1
carbon-carbon lyase activity	1
nuclear lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1818 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UROD	CPOX	P36551	976
UROD	ALAD	P13716	975
UROD	HMBS	P08396	965
UROD	PPOX	P50336	949
UROD	UROS	P10746	918
UROD	FECH	P22830	867
UROD	HFE	Q30201	856
UROD	ALAS1	P13196	839
UROD	ALAS2	P22557	742
UROD	CYP1A2	P05177	684
UROD	TFRC	P02786	679
UROD	SLC25A38	Q96DW6	642
UROD	ABCB6	Q9NP58	613
UROD	TDO2	P48775	573
UROD	BLVRA	P53004	545

IntAct

41 interactions, top by confidence:

A	B	Type	Score
LRATD2	UROD	psi-mi:“MI:0915”(physical association)	0.780
UROD	LRATD2	psi-mi:“MI:0915”(physical association)	0.780
UROD	POTEF	psi-mi:“MI:0915”(physical association)	0.590
PPID	UROD	psi-mi:“MI:0915”(physical association)	0.590
PILRA	UROD	psi-mi:“MI:0915”(physical association)	0.560
UROD	TSSK3	psi-mi:“MI:0915”(physical association)	0.560
UROD	PHKA2	psi-mi:“MI:0915”(physical association)	0.560
EGFR	UROD	psi-mi:“MI:0915”(physical association)	0.550
CPNE5	RAD21	psi-mi:“MI:0914”(association)	0.530
UROD	Urod	psi-mi:“MI:0915”(physical association)	0.400
UROD	CHD3	psi-mi:“MI:0915”(physical association)	0.370
UROD	FAF1	psi-mi:“MI:0915”(physical association)	0.370
HMGXB4	UROD	psi-mi:“MI:0915”(physical association)	0.370
VIM	UROD	psi-mi:“MI:0915”(physical association)	0.370
CPNE5	NCK2	psi-mi:“MI:0914”(association)	0.350
pipB2	PSMD12	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
TCF4	INHA	psi-mi:“MI:0914”(association)	0.350
TMEM129	INHA	psi-mi:“MI:0914”(association)	0.350
UROD	C3	psi-mi:“MI:0914”(association)	0.350
PILRA	UROD	psi-mi:“MI:0915”(physical association)	0.000
UROD	PHKA2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (51): FAM84B (Two-hybrid), UROD (Affinity Capture-RNA), UROD (Affinity Capture-RNA), POTEF (Affinity Capture-MS), WDR45B (Affinity Capture-MS), MYCBP (Co-fractionation), TIPRL (Co-fractionation), UROD (Affinity Capture-MS), POTEF (Affinity Capture-MS), UROD (Affinity Capture-MS), UROD (Biochemical Activity), UROD (Proximity Label-MS), UROD (Affinity Capture-RNA), UROD (Two-hybrid), UROD (Two-hybrid)

ESM2 similar proteins: A1AIG8, A1S2J2, A1VJ58, A2SC07, A4W5C0, A6T450, A6TGQ4, A7MJ78, A8FQD0, B0KN28, B1WVY1, B2J9R9, B2SKP7, B2VG77, B5XYE1, B5Z093, B7LUK5, B7MIY3, B7N2J9, B7NRT0, B7UPF2, C3KBH3, C5BHE8, C5BRJ3, C5CLI6, P06132, P16891, P32362, P54224, P57964, P70697, Q0A4Y2, Q0I5E2, Q12S16, Q1R5W3, Q2JKH3, Q2JX97, Q2NWR2, Q2P6D1, Q31U00

Diamond homologs: A0M6C4, A1AIG8, A1BCW4, A1SZJ4, A3MYI4, A4SGN6, A4W5C0, A4XPQ6, A5FLE7, A5IDL1, A6GVN8, A6VDF5, A6VQT2, A7FNH2, A7N075, A7ZUL3, A8A797, A8AKS6, A8FQD0, A8G8F7, A9KCZ5, A9NB09, B0BS17, B0KN28, B0US07, B1IUQ0, B1J2J9, B1KN91, B1LNU9, B1XC00, B2TWI4, B3EHV5, B3EL29, B3GZV2, B3QL69, B3QXB5, B4EYT8, B4S3W2, B4SGD6, B5FC78

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

202 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	19
Uncertain significance	91
Likely benign	20
Benign	5

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1353137	NM_000374.5(UROD):c.385_386insAGT (p.Ser129Ter)	Pathogenic
1455082	NM_000374.5(UROD):c.497T>C (p.Val166Ala)	Pathogenic
1459078	NC_000001.10:g.(?45478583)(45479635_?)del	Pathogenic
1695444	NM_000374.5(UROD):c.430C>T (p.Arg144Ter)	Pathogenic
2202750	NM_000374.5(UROD):c.238G>T (p.Ala80Ser)	Pathogenic
2633059	NM_000374.5(UROD):c.943-1G>A	Pathogenic
2733886	NM_000374.5(UROD):c.96del (p.Val33fs)	Pathogenic
2733887	NM_000374.5(UROD):c.239C>G (p.Ala80Gly)	Pathogenic
2733891	NM_000374.5(UROD):c.874del (p.Arg292fs)	Pathogenic
2826063	NM_000374.5(UROD):c.635del (p.Gln212fs)	Pathogenic
2907277	NM_000374.5(UROD):c.812_842del (p.Glu271fs)	Pathogenic
3063966	NM_000374.5(UROD):c.651dup (p.Glu218Ter)	Pathogenic
3370430	NM_000374.5(UROD):c.186dup (p.Glu63Ter)	Pathogenic
3380963	NM_000374.5(UROD):c.398_399del (p.Tyr133fs)	Pathogenic
3639318	NM_000374.5(UROD):c.89del (p.Tyr30fs)	Pathogenic
3664190	NM_000374.5(UROD):c.820C>T (p.Gln274Ter)	Pathogenic
3720199	NM_000374.5(UROD):c.102G>A (p.Trp34Ter)	Pathogenic
3910501	NM_000374.5(UROD):c.400G>C (p.Val134Leu)	Pathogenic
64679	NM_000374.5(UROD):c.346C>T (p.Gln116Ter)	Pathogenic
66	NM_000374.5(UROD):c.842G>A (p.Gly281Glu)	Pathogenic
67	NM_000374.5(UROD):c.636+1G>C	Pathogenic
69	NM_000374.5(UROD):c.874C>G (p.Arg292Gly)	Pathogenic
70	NM_000374.5(UROD):c.185C>T (p.Pro62Leu)	Pathogenic
74	NM_000374.5(UROD):c.583C>T (p.Leu195Phe)	Pathogenic
75	NM_000374.5(UROD):c.912C>A (p.Asn304Lys)	Pathogenic
801474	NM_000374.5(UROD):c.904C>T (p.Gln302Ter)	Pathogenic
915319	NM_000374.5(UROD):c.21-1G>C	Pathogenic
986911	NM_000374.5(UROD):c.203_207dup (p.Leu70Ter)	Pathogenic
1067802	NM_000374.5(UROD):c.133+1del	Likely pathogenic
1298341	NM_000374.5(UROD):c.583_611del (p.Leu195fs)	Likely pathogenic

SpliceAI

1304 predictions. Top by Δscore:

Variant	Effect	Δscore
1:45012897:T:TA	acceptor_gain	1.0000
1:45013018:AGGT:A	donor_loss	1.0000
1:45013019:GGT:G	donor_loss	1.0000
1:45013020:GT:G	donor_loss	1.0000
1:45013690:G:GT	donor_gain	1.0000
1:45013708:C:G	donor_gain	1.0000
1:45013712:GC:G	donor_gain	1.0000
1:45013713:C:G	donor_gain	1.0000
1:45013757:G:GT	donor_gain	1.0000
1:45013757:G:T	donor_gain	1.0000
1:45013792:G:GG	donor_gain	1.0000
1:45013907:A:AG	acceptor_gain	1.0000
1:45013907:AGT:A	acceptor_gain	1.0000
1:45013908:G:GG	acceptor_gain	1.0000
1:45013908:GT:G	acceptor_gain	1.0000
1:45013908:GTG:G	acceptor_gain	1.0000
1:45014832:GCCCG:G	donor_gain	1.0000
1:45014836:GGTAA:G	donor_loss	1.0000
1:45014837:G:GC	donor_loss	1.0000
1:45014837:G:GG	donor_gain	1.0000
1:45012894:ACCT:A	acceptor_gain	0.9900
1:45013020:G:GG	donor_gain	0.9900
1:45013021:T:G	donor_loss	0.9900
1:45013290:A:AG	acceptor_gain	0.9900
1:45013291:G:GG	acceptor_gain	0.9900
1:45013350:CCCAG:C	donor_loss	0.9900
1:45013351:CCAG:C	donor_loss	0.9900
1:45013352:CAGGT:C	donor_loss	0.9900
1:45013353:AG:A	donor_loss	0.9900
1:45013354:GGTA:G	donor_loss	0.9900

AlphaMissense

2364 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:45013335:A:T	D86V	0.999
1:45013777:T:C	F154L	0.999
1:45013779:T:A	F154L	0.999
1:45013779:T:G	F154L	0.999
1:45013328:T:C	F84L	0.998
1:45013330:C:A	F84L	0.998
1:45013330:C:G	F84L	0.998
1:45012986:T:A	W34R	0.997
1:45012986:T:C	W34R	0.997
1:45013138:T:C	F46L	0.997
1:45013140:T:A	F46L	0.997
1:45013140:T:G	F46L	0.997
1:45013335:A:C	D86A	0.997
1:45013335:A:G	D86G	0.997
1:45013334:G:C	D86H	0.995
1:45013336:C:A	D86E	0.995
1:45013336:C:G	D86E	0.995
1:45014451:T:C	F217L	0.995
1:45014453:T:A	F217L	0.995
1:45014453:T:G	F217L	0.995
1:45013778:T:C	F154S	0.994
1:45012995:C:A	R37S	0.993
1:45013000:G:C	Q38H	0.993
1:45013000:G:T	Q38H	0.993
1:45013334:G:T	D86Y	0.993
1:45013909:T:A	W159R	0.993
1:45013909:T:C	W159R	0.993
1:45015402:C:A	N336K	0.993
1:45015402:C:G	N336K	0.993
1:45012994:G:A	M36I	0.992

dbSNP variants (sampled 300 via entrez): RS1000689718 (1:45010979 G>A), RS1001053303 (1:45012627 T>C), RS1001647308 (1:45012776 G>A), RS1001840437 (1:45013217 T>C), RS1001908940 (1:45011268 C>T), RS1001953903 (1:45011740 C>A,G,T), RS1003918163 (1:45011652 A>T), RS1004430579 (1:45011462 C>G), RS1004483818 (1:45011291 C>T), RS1005587216 (1:45012016 C>A,G,T), RS1008269483 (1:45010653 C>A,G,T), RS1009175901 (1:45012670 G>A,C,T), RS1010753271 (1:45012094 C>A,T), RS1010904769 (1:45015652 C>G,T), RS1010988127 (1:45015060 G>A)

Disease associations

OMIM: gene MIM:613521 | disease phenotypes: MIM:176100, MIM:176090

GenCC curated gene-disease

Disease	Classification	Inheritance
UROD-related inherited porphyria	Definitive	Semidominant
familial porphyria cutanea tarda	Strong	Autosomal dominant
hepatoerythropoietic porphyria	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
UROD-related inherited porphyria	Definitive	SD

Mondo (5): familial porphyria cutanea tarda (MONDO:0008296), UROD-related inherited porphyria (MONDO:0100498), porphyria cutanea tarda (MONDO:0015104), hepatoerythropoietic porphyria (MONDO:0019799), sporadic porphyria cutanea tarda (MONDO:0008295)

Orphanet (4): Porphyria cutanea tarda (Orphanet:101330), Familial porphyria cutanea tarda (Orphanet:443062), Hepatoerythropoietic porphyria (Orphanet:95159), Sporadic porphyria cutanea tarda (Orphanet:443057)

HPO phenotypes

48 total (30 of 48 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000618	Blindness
HP:0000656	Ectropion
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000953	Hyperpigmentation of the skin
HP:0000969	Edema
HP:0000989	Pruritus
HP:0000992	Cutaneous photosensitivity
HP:0001010	Hypopigmentation of the skin
HP:0001030	Fragile skin
HP:0001072	Thickened skin
HP:0001096	Keratoconjunctivitis
HP:0001394	Cirrhosis
HP:0001402	Hepatocellular carcinoma
HP:0001560	Abnormality of the amniotic fluid
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001790	Nonimmune hydrops fetalis
HP:0001806	Onycholysis
HP:0001878	Hemolytic anemia
HP:0001892	Abnormal bleeding
HP:0002219	Facial hypertrichosis
HP:0002797	Osteolysis
HP:0003401	Paresthesia
HP:0004552	Scarring alopecia of scalp
HP:0005406	Recurrent bacterial skin infections
HP:0005586	Hyperpigmentation in sun-exposed areas
HP:0007537	Severe photosensitivity

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D017119	Porphyria Cutanea Tarda	C06.552.830.100; C16.320.850.742.250; C17.800.827.742.250; C18.452.811.400.250
D017121	Porphyria, Hepatoerythropoietic	C06.552.830.437; C16.320.850.742.437; C17.800.827.742.437; C18.452.811.400.437
C566768	Porphyria Cutanea Tarda, Type I (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1681619 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	decreases expression, increases abundance	2
Acetaminophen	decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
ochratoxin A	increases expression	1
coumarin	increases phosphorylation	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
K 7174	decreases expression	1
scopolin	affects activity, affects binding	1
nodakenin	affects activity, affects binding	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
isopraeroside IV	affects activity, affects binding	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Alcohols	decreases activity	1
Arsenic	decreases expression, increases abundance	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1676175	Binding	Activity at recombinant URO-D assessed as product formation after 30 mins	Normal and abnormal heme biosynthesis. Part 7. Synthesis and metabolism of coproporphyrinogen-III analogues with acetate or butyrate side chains on rings C and D. Development of a modified model for the active site of coproporphyrinogen oxidase. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 6 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B0GW	LB44	Transformed cell line	Sex unspecified
CVCL_B0GX	LB44-LUDSN11	Transformed cell line	Sex unspecified
CVCL_B0GY	LB45	Transformed cell line	Sex unspecified
CVCL_B0GZ	LB45-LUDSN11	Transformed cell line	Sex unspecified
CVCL_B0H0	LB86	Transformed cell line	Sex unspecified
CVCL_B0H1	LB86-LUDSN11	Transformed cell line	Sex unspecified

Clinical trials (associated diseases)

7 trials via MONDO — disease-level, not drug-specific.

Trial	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
NCT03388944	Not specified	COMPLETED	PCT Guided Stopping of Antibiotic Therapy in Children With Sepsis
NCT00005103	Not specified	COMPLETED	Study of the Pathogenesis of Porphyria Cutanea Tarda
NCT00213772	Not specified	COMPLETED	Risk Factors of Porphyria Cutanea Tarda (PCT)