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    UROS uroporphyrinogen III synthase [ Homo sapiens (human) ]

    Gene ID: 7390, updated on 27-Nov-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
    mouse all
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    Genomic context

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    See UROS in Genome Data Viewer
    Location:
    10q26.2
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (125784980..125823258, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (126667433..126705738, complement)
    RS_2024_09 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. 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
    2. C73R is a hotspot mutation in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria. Frank J, et al. Ann Hum Genet, 1998 May. PMID 9803266
    3. Congenital erythropoietic porphyria successfully treated by allogeneic bone marrow transplantation. Tezcan I, et al. Blood, 1998 Dec 1. PMID 9834209
    4. Congenital erythropoietic porphyria: a novel homozygous mutation in a Japanese patient. Rogounovitch T, et al. J Invest Dermatol, 2000 Dec. PMID 11121156
    5. Uroporphyrinogen III synthase erythroid promoter mutations in adjacent GATA1 and CP2 elements cause congenital erythropoietic porphyria. Solis C, et al. J Clin Invest, 2001 Mar. PMID 11254675, 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
    		not available

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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_2024_08

    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

    Gene LinkOut

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