GeneBe

UROD

uroporphyrinogen decarboxylase

Basic information

Region (hg38): 1:45010950-45015575

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
  • UROD-related inherited porphyria (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Porphyria, hepatoerythropoietic; Porphyria cutanea tardaAD/ARDermatologic; Hematologic; PharmacogenomicTreatment 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 warrantedBiochemical; Dermatologic; Gastrointestinal; Hematologic5697519; 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 (118 variants)
  • Familial_porphyria_cutanea_tarda (44 variants)
  • Inborn_genetic_diseases (17 variants)
  • UROD-related_disorder (12 variants)
  • not_specified (7 variants)
  • Hepatoerythropoietic_porphyria (5 variants)
  • Porphyria_cutanea_tarda (3 variants)
  • Sporadic_porphyria_cutanea_tarda (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. These statistics are base on transcript: NM_000000374.5. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
2
clinvar
9
clinvar
 12
missense
10
clinvar
12
clinvar
65
clinvar
7
clinvar
 94
nonsense
10
clinvar
4
clinvar
 14
start loss
1
 1
frameshift
10
clinvar
5
clinvar
 15
splice donor/acceptor (+/-2bp)
4
clinvar
4
clinvar
 8
Total 35 26 67 16 0

Highest pathogenic variant AF is 0.000118328

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
URODprotein_codingprotein_codingENST00000246337 103429
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.26e-80.5741256920561257480.000223
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.111652100.7840.00001222358
Missense in Polyphen6399.5910.632591151
Synonymous0.7347078.30.8940.00000388767
Loss of Function1.131520.50.7310.00000109226

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0008530.000853
Ashkenazi Jewish0.000.00
East Asian0.0001630.000163
Finnish0.00004620.0000462
European (Non-Finnish)0.0001760.000176
Middle Eastern0.0001630.000163
South Asian0.0002290.000229
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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