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UROS uroporphyrinogen III synthase [ Homo sapiens (human) ]

Gene ID: 7390, updated on 3-Apr-2024

Summary

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Official Symbol
UROSprovided by HGNC
Official Full Name
uroporphyrinogen III synthaseprovided by HGNC
Primary source
HGNC:HGNC:12592
See related
Ensembl:ENSG00000188690 MIM:606938; AllianceGenome:HGNC:12592
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
UROIIIS
Summary
The protein encoded by this gene catalyzes the fourth step of porphyrin biosynthesis in the heme biosynthetic pathway. Defects in this gene cause congenital erythropoietic porphyria (Gunther's disease). [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in bone marrow (RPKM 4.5), brain (RPKM 4.4) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
10q26.2
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (125784980..125823258, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (126667433..126705738, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (127473549..127511827, complement)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene erythroid differentiation regulatory factor 1 Neighboring gene EDRF1 antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 6903 Neighboring gene matrix metallopeptidase 21 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2924 Neighboring gene CRISPRi-validated UROS cis-regulatory element Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:127511755-127512440 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:127512660-127512879 Neighboring gene microRNA 4484 Neighboring gene BRCA2 and CDKN1A interacting protein Neighboring gene ReSE screen-validated silencer GRCh37_chr10:127541940-127542119 Neighboring gene DEAH-box helicase 32 (putative) Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:127569451-127570173 Neighboring gene Sharpr-MPRA regulatory region 1957 Neighboring gene RNA, U2 small nuclear 42, pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Missense UROS mutations causing congenital erythropoietic porphyria reduce UROS homeostasis that can be rescued by proteasome inhibition. Blouin JM, et al. Hum Mol Genet, 2017 Apr 15. PMID 28334762
  2. Mutational analysis of uroporphyrinogen III cosynthase gene in Iranian families with congenital erythropoietic porphyria. Moghbeli M, et al. Mol Biol Rep, 2012 Jun. PMID 22350154
  3. Structural, thermodynamic, and mechanistical studies in uroporphyrinogen III synthase: molecular basis of congenital erythropoietic porphyria. Fortian A, et al. Adv Protein Chem Struct Biol, 2011. PMID 21570665
  4. Intracellular rescue of the uroporphyrinogen III synthase activity in enzymes carrying the hotspot mutation C73R. Fortian A, et al. J Biol Chem, 2011 Apr 15. PMID 21343304, Free PMC Article
  5. Congenital erythropoietic porphyria: a novel uroporphyrinogen III synthase branchpoint mutation reveals underlying wild-type alternatively spliced transcripts. Bishop DF, et al. Blood, 2010 Feb 4. PMID 19965637, Free PMC Article

See all (49) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. These results expand the molecular heterogeneity of the erythropoietic porphyrias by adding a total of 7 novel mutations in uroporphyrinogen III synthase.
    Title: Congenital erythropoietic porphyria and erythropoietic protoporphyria: Identification of 7 uroporphyrinogen III synthase and 20 ferrochelatase novel mutations.
  2. we show evidence that abnormal protein homeostasis is a prevalent mechanism responsible for UROS deficiency and that modulators of UROS proteolysis such as proteasome inhibitors or chemical chaperones may represent an attractive therapeutic option to reduce porphyrin accumulation and prevent skin photosensitivity in Congenital erythropoietic porphyria (CEP)patients when the genotype includes a missense variant.
    Title: Missense UROS mutations causing congenital erythropoietic porphyria reduce UROS homeostasis that can be rescued by proteasome inhibition.
  3. A, T to C change at nucleotide 34313, leading to a substitution of Leucine by Proline at codon 237, was observed in the homozygous state in a family with congenital erythropoietic porphyria.
    Title: Mutational analysis of uroporphyrinogen III cosynthase gene in Iranian families with congenital erythropoietic porphyria.
  4. REVIEW: Structural, thermodynamic, and mechanistical studies in uroporphyrinogen III synthase and molecular basis of congenital erythropoietic porphyria
    Title: Structural, thermodynamic, and mechanistical studies in uroporphyrinogen III synthase: molecular basis of congenital erythropoietic porphyria.
  5. Intracellular rescue of the uroporphyrinogen III synthase activity in enzymes carrying the hotspot mutation C73R.
    Title: Intracellular rescue of the uroporphyrinogen III synthase activity in enzymes carrying the hotspot mutation C73R.
  6. Data show that branchpoint sequence (BPS)mutation reduced the wild-type transcript and UROS enzyme activity in CEP lymphoblasts to approximately 10% and 15% of normal, respectively.
    Title: Congenital erythropoietic porphyria: a novel uroporphyrinogen III synthase branchpoint mutation reveals underlying wild-type alternatively spliced transcripts.
  7. UROS mutations related to erythropoietic porphyria identify a key helix for protein stability.
    Title: Uroporphyrinogen III synthase mutations related to congenital erythropoietic porphyria identify a key helix for protein stability.
  8. The decrease in the expression of ubiquitous HMBS and UROS mRNAs under hypoxia is associated with accumulation of hypoxia-inducible factor 1alpha protein.
    Title: Hypoxia decreases the expression of the two enzymes responsible for producing linear and cyclic tetrapyrroles in the heme biosynthetic pathway.
  9. NMR analyses of URO-synthase titrated with competitive inhibitors N(D)-methyl-1-formylbilane or URO'gen III, revealed resonance perturbations of specific residues lining the cleft between 2 major domains of URO synthase that mapped enzyme's active site.
    Title: Human uroporphyrinogen III synthase: NMR-based mapping of the active site.
  10. two novel misense mutations in the UROS gene.
    Title: Identification of mutations in the uroporphyrinogen III cosynthase gene in German patients with congenital erythropoietic porphyria.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Cutaneous porphyria
MedGen: C0162530 OMIM: 263700 GeneReviews: Congenital Erythropoietic Porphyria
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables folic acid binding IEA
Inferred from Electronic Annotation
more info
  
enables uroporphyrinogen-III synthase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables uroporphyrinogen-III synthase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables uroporphyrinogen-III synthase activity TAS
Traceable Author Statement
more info
  
Process Evidence Code Pubs
involved_in cellular response to amine stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to arsenic-containing substance IEA
Inferred from Electronic Annotation
more info
  
involved_in heme A biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in heme B biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in heme O biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in heme biosynthetic process IC
Inferred by Curator
more info
 PubMed 
involved_in heme biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in heme biosynthetic process TAS
Traceable Author Statement
more info
  
involved_in protoporphyrinogen IX biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in response to platinum ion IEA
Inferred from Electronic Annotation
more info
  
involved_in uroporphyrinogen III biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in uroporphyrinogen III biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol NAS
Non-traceable Author Statement
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in mitochondrion ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
uroporphyrinogen-III synthase
Names
hydroxymethylbilane hydrolyase
uroporphyrinogen-III cosynthase
NP_000366.1
NP_001310965.1
NP_001310966.1
NP_001310967.1
NP_001310968.1
XP_005270197.1
XP_011538429.1
XP_016872100.2
XP_016872101.1
XP_024303922.1
XP_024303923.1
XP_047281664.1
XP_047281665.1
XP_047281666.1
XP_047281667.1
XP_054222649.1
XP_054222650.1
XP_054222651.1
XP_054222652.1
XP_054222653.1
XP_054222654.1
XP_054222655.1
XP_054222656.1
XP_054222657.1
XP_054222658.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011557.2 RefSeqGene

    Range
    5011..39683
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1081

mRNA and Protein(s)

  1. NM_000375.3 → NP_000366.1  uroporphyrinogen-III synthase isoform 2

    See identical proteins and their annotated locations for NP_000366.1

    Status: REVIEWED

    Source sequence(s)
    BC002573, DR156879
    Consensus CDS
    CCDS7648.1
    UniProtKB/Swiss-Prot
    B2RC13, D3DRF7, P10746, Q9H2T1
    UniProtKB/TrEMBL
    A0A0S2Z4T8
    Related
    ENSP00000357787.4, ENST00000368797.10
    Conserved Domains (1) summary
    cd06578
    Location:3 → 255
    HemD; Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in ...

  2. NM_001324036.2 → NP_001310965.1  uroporphyrinogen-III synthase isoform 1

    Status: REVIEWED

    Source sequence(s)
    AL360176
    Consensus CDS
    CCDS91372.1
    UniProtKB/TrEMBL
    A0A3B3ISM6
    Conserved Domains (1) summary
    cd06578
    Location:3 → 282
    HemD; Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in ...

  3. NM_001324037.2 → NP_001310966.1  uroporphyrinogen-III synthase isoform 3

    Status: REVIEWED

    Source sequence(s)
    AL360176
    Consensus CDS
    CCDS91371.1
    UniProtKB/TrEMBL
    A0A3B3ITJ2
    Related
    ENSP00000497817.1, ENST00000649536.1
    Conserved Domains (1) summary
    cd06578
    Location:3 → 255
    HemD; Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in ...

  4. NM_001324038.2 → NP_001310967.1  uroporphyrinogen-III synthase isoform 4

    Status: REVIEWED

    Source sequence(s)
    AL360176
    UniProtKB/TrEMBL
    A0A0S2Z5C5
    Conserved Domains (1) summary
    cd06578
    Location:3 → 228
    HemD; Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in ...

  5. NM_001324039.2 → NP_001310968.1  uroporphyrinogen-III synthase isoform 5

    Status: REVIEWED

    Source sequence(s)
    AL360176
    Consensus CDS
    CCDS81522.1
    UniProtKB/TrEMBL
    D3DRF8, Q5T3L7, Q5T3L8
    Related
    ENSP00000357767.3, ENST00000368778.7
    Conserved Domains (1) summary
    cd06578
    Location:3 → 130
    HemD; Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in ...

RNA

  1. NR_136675.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL360176

  2. NR_136676.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL360176

  3. NR_136677.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL360176

  4. NR_136678.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL360176, BI668388

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    125784980..125823258 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011540127.3 → XP_011538429.1  uroporphyrinogen-III synthase isoform X5

    Conserved Domains (1) summary
    cd06578
    Location:3 → 221
    HemD; Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in ...

  2. XM_017016612.3 → XP_016872101.1  uroporphyrinogen-III synthase isoform X4

    Conserved Domains (1) summary
    cd06578
    Location:3 → 221
    HemD; Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in ...

  3. XM_047425708.1 → XP_047281664.1  uroporphyrinogen-III synthase isoform X3

    UniProtKB/TrEMBL
    A0A3B3ITJ2

  4. XM_024448154.2 → XP_024303922.1  uroporphyrinogen-III synthase isoform X2

    UniProtKB/Swiss-Prot
    B2RC13, D3DRF7, P10746, Q9H2T1
    UniProtKB/TrEMBL
    A0A0S2Z4T8
    Related
    ENSP00000357775.1, ENST00000368786.5
    Conserved Domains (1) summary
    cd06578
    Location:3 → 255
    HemD; Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in ...

  5. XM_017016611.3 → XP_016872100.2  uroporphyrinogen-III synthase isoform X1

    UniProtKB/TrEMBL
    A0A3B3ISM6
    Related
    ENSP00000497366.1, ENST00000650587.1
    Conserved Domains (1) summary
    cd06578
    Location:3 → 282
    HemD; Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in ...

  6. XM_047425709.1 → XP_047281665.1  uroporphyrinogen-III synthase isoform X6

  7. XM_024448155.2 → XP_024303923.1  uroporphyrinogen-III synthase isoform X7

    UniProtKB/TrEMBL
    Q5T3L9
    Conserved Domains (1) summary
    cd06578
    Location:3 → 193
    HemD; Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in ...

  8. XM_005270140.6 → XP_005270197.1  uroporphyrinogen-III synthase isoform X6

    See identical proteins and their annotated locations for XP_005270197.1

    UniProtKB/TrEMBL
    Q5T3L9
    Related
    ENSP00000414833.1, ENST00000420761.5
    Conserved Domains (1) summary
    cd06578
    Location:3 → 220
    HemD; Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in ...

  9. XM_047425710.1 → XP_047281666.1  uroporphyrinogen-III synthase isoform X8

    Related
    ENSP00000497494.1, ENST00000648119.1

  10. XM_047425711.1 → XP_047281667.1  uroporphyrinogen-III synthase isoform X9

    UniProtKB/TrEMBL
    D3DRF8, Q5T3L8

RNA

  1. XR_007061985.1 RNA Sequence

  2. XR_001747196.3 RNA Sequence

  3. XR_007061986.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    126667433..126705738 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054366678.1 → XP_054222653.1  uroporphyrinogen-III synthase isoform X5

  2. XM_054366677.1 → XP_054222652.1  uroporphyrinogen-III synthase isoform X4

  3. XM_054366675.1 → XP_054222650.1  uroporphyrinogen-III synthase isoform X2

  4. XM_054366676.1 → XP_054222651.1  uroporphyrinogen-III synthase isoform X3

  5. XM_054366674.1 → XP_054222649.1  uroporphyrinogen-III synthase isoform X1

  6. XM_054366680.1 → XP_054222655.1  uroporphyrinogen-III synthase isoform X6

  7. XM_054366681.1 → XP_054222656.1  uroporphyrinogen-III synthase isoform X7

  8. XM_054366679.1 → XP_054222654.1  uroporphyrinogen-III synthase isoform X6

  9. XM_054366682.1 → XP_054222657.1  uroporphyrinogen-III synthase isoform X8

  10. XM_054366683.1 → XP_054222658.1  uroporphyrinogen-III synthase isoform X9

RNA

  1. XR_008488261.1 RNA Sequence

  2. XR_008488260.1 RNA Sequence

  3. XR_008488262.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P10746.1 GenPept UniProtKB/Swiss-Prot:P10746

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