UROD

uroporphyrinogen decarboxylase

Basic information

Region (hg38): 1:45010949-45015575

Links

ENSG00000126088 ∙ NCBI:7389 ∙ OMIM:613521 ∙ HGNC:12591 ∙ Uniprot:P06132 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial porphyria cutanea tarda (Strong), mode of inheritance: AD
• familial porphyria cutanea tarda (Strong), mode of inheritance: AR
• hepatoerythropoietic porphyria (Supportive), mode of inheritance: AR
• familial porphyria cutanea tarda (Supportive), mode of inheritance: AD
• familial porphyria cutanea tarda (Strong), mode of inheritance: AD
• familial porphyria cutanea tarda (Strong), mode of inheritance: AR
• UROD-related inherited porphyria (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Porphyria, hepatoerythropoietic; Porphyria cutanea tarda	AD/AR	Dermatologic; Hematologic; Pharmacogenomic	Treatment involves management of iron overload (eg, by phlebotomy); Exacerbating factors (eg, iron overload, excessive alcohol use, polyhalogenated aromatic chemicals, estrogens, etc.) should be avoided; Skin protection is warranted	Biochemical; Dermatologic; Gastrointestinal; Hematologic	5697519; 5455563; 4640947; 5080345; 4729688; 4739135; 993332; 871403; 730158; 661929; 758588; 463934; 253381; 7369748; 7428280; 6112327; 7062951; 7059676; 6375356; 3775362; 3808000; 3821794; 3348969; 2920211; 1442894; 8644733; 9792863; 12030801; 17295179; 20955974; 21668429; 22382040; 23545314

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UROD gene.

• not provided (84 variants)
• Familial porphyria cutanea tarda (39 variants)
• Inborn genetic diseases (9 variants)
• not specified (6 variants)
• Porphyria cutanea tarda (6 variants)
• UROD-related condition (4 variants)
• Hepatoerythropoietic porphyria (4 variants)
• Sporadic porphyria cutanea tarda (1 variants)
• UROD-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UROD gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	3	1	7
missense	7	4	36	2		49
nonsense	4	3				7
start loss	1					1
frameshift	2	4				6
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)	4	2				6
splice region		1	2	1		4
non coding			15	5	3	23
Total	18	14	55	10	4

Highest pathogenic variant AF is 0.0000329

Variants in UROD

This is a list of pathogenic ClinVar variants found in the UROD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-45010980-C-A		not specified	Uncertain significance (Aug 10, 2021)
1-45011050-C-T		not specified	Uncertain significance (Sep 17, 2021)
1-45011142-G-A		not specified	Uncertain significance (Aug 15, 2023)
1-45011223-G-A		not specified	Uncertain significance (Jun 11, 2021)
1-45011241-G-A		not specified	Uncertain significance (Aug 16, 2022)
1-45012132-T-G		Porphyria cutanea tarda	Likely benign (Jun 14, 2016)
1-45012199-G-A		Porphyria cutanea tarda	Uncertain significance (Jun 14, 2016)
1-45012203-T-TG		Porphyria cutanea tarda	Uncertain significance (Jun 14, 2016)
1-45012214-C-A		Porphyria cutanea tarda	Uncertain significance (Jun 14, 2016)
1-45012215-T-C		Porphyria cutanea tarda	Uncertain significance (Jun 14, 2016)
1-45012265-C-T		Familial porphyria cutanea tarda	Uncertain significance (Jan 12, 2018)
1-45012268-G-A			Pathogenic (Dec 20, 2022)
1-45012270-AAGCGAATGGG-A		Porphyria cutanea tarda	Pathogenic (Apr 01, 2009)
1-45012286-G-T			Pathogenic (Apr 25, 2023)
1-45012890-C-G			Uncertain significance (Oct 09, 2023)
1-45012890-C-T			Likely benign (Jan 05, 2024)
1-45012895-C-G			Uncertain significance (May 23, 2023)
1-45012895-C-T		Familial porphyria cutanea tarda	Uncertain significance (Jan 12, 2018)
1-45012897-T-A		UROD-related disorder	Likely benign (Aug 08, 2023)
1-45012906-G-C		Familial porphyria cutanea tarda	Pathogenic (May 03, 2020)
1-45012913-G-C		Familial porphyria cutanea tarda	Uncertain significance (Nov 13, 2022)
1-45012956-T-G		Familial porphyria cutanea tarda	Uncertain significance (Jan 19, 2024)
1-45012959-G-A			Uncertain significance (May 30, 2023)
1-45012960-G-A			Uncertain significance (Oct 16, 2022)
1-45012966-A-T			Uncertain significance (Sep 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UROD	protein_coding	protein_coding	ENST00000246337	10	3429

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.26e-8	0.574	125692	0	56	125748	0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.11	165	210	0.784	0.0000122	2358
Missense in Polyphen		63	99.591	0.63259		1151
Synonymous	0.734	70	78.3	0.894	0.00000388	767
Loss of Function	1.13	15	20.5	0.731	0.00000109	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000853	0.000853
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000176	0.000176
Middle Eastern	0.000163	0.000163
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the decarboxylation of four acetate groups of uroporphyrinogen-III to yield coproporphyrinogen-III.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:10338097, ECO:0000269|PubMed:10477430, ECO:0000269|PubMed:11069625, ECO:0000269|PubMed:11295834, ECO:0000269|PubMed:11719352, ECO:0000269|PubMed:2243121, ECO:0000269|PubMed:2920211, ECO:0000269|PubMed:7706766, ECO:0000269|PubMed:8896428, ECO:0000269|PubMed:9792863}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:12071824, ECO:0000269|PubMed:15491440, ECO:0000269|PubMed:1634232, ECO:0000269|PubMed:17240319, ECO:0000269|PubMed:1905636, ECO:0000269|PubMed:21668429, ECO:0000269|PubMed:3775362, ECO:0000269|PubMed:8176248, ECO:0000269|PubMed:8644733, ECO:0000269|PubMed:8896428}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Porphyrin and chlorophyll metabolism - Homo sapiens (human);Hereditary Coproporphyria (HCP);Porphyria Variegata (PV);Congenital Erythropoietic Porphyria (CEP) or Gunther Disease;Acute Intermittent Porphyria;Porphyrin Metabolism;Heme Biosynthesis;hemoglobins chaperone;Heme biosynthesis;Metabolism of porphyrins;Metabolism;Porphyrin metabolism;heme biosynthesis from uroporphyrinogen-III I;heme biosynthesis (Consensus)

Recessive Scores

• pRec: 0.229

Intolerance Scores

• loftool: 0.180
• rvis_EVS: 0.11
• rvis_percentile_EVS: 61.73

Haploinsufficiency Scores

• pHI: 0.559
• hipred: N
• hipred_score: 0.285
• ghis: 0.496

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Urod
• Phenotype: homeostasis/metabolism phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype

Zebrafish Information Network

• Gene name: urod
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: increased fluorescence

Gene ontology

• Biological process: protoporphyrinogen IX biosynthetic process;heme biosynthetic process
• Cellular component: nucleoplasm;cytosol
• Molecular function: uroporphyrinogen decarboxylase activity;protein binding