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    HMBS hydroxymethylbilane synthase [ Homo sapiens (human) ]

    Gene ID: 3145, updated on 2-Mar-2024

    Summary

    Official Symbol
    HMBSprovided by HGNC
    Official Full Name
    hydroxymethylbilane synthaseprovided by HGNC
    Primary source
    HGNC:HGNC:4982
    See related
    Ensembl:ENSG00000256269 MIM:609806; AllianceGenome:HGNC:4982
    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
    UPS; PBGD; PORC; ENCEP; PBG-D; LENCEP
    Summary
    This gene encodes a member of the hydroxymethylbilane synthase superfamily. The encoded protein is the third enzyme of the heme biosynthetic pathway and catalyzes the head to tail condensation of four porphobilinogen molecules into the linear hydroxymethylbilane. Mutations in this gene are associated with the autosomal dominant disease acute intermittent porphyria. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in bone marrow (RPKM 55.8), colon (RPKM 5.0) and 13 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See HMBS in Genome Data Viewer
    Location:
    11q23.3
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (119084881..119093549)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (119105272..119113932)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (118955591..118964259)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124902769 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5619 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5620 Neighboring gene VPS11 core subunit of CORVET and HOPS complexes Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:118955192-118955889 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:118963458-118963970 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:118965105-118965668 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:118965669-118966232 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:118966233-118966796 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:118966797-118967358 Neighboring gene dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 Neighboring gene H2A.X variant histone Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr11:118972216-118973415 Neighboring gene C2CD2 like Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3968 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3969

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Acute intermittent porphyria
    MedGen: C0162565 OMIM: 176000 GeneReviews: Acute Intermittent Porphyria
    Compare labs
    ENCEPHALOPATHY, PORPHYRIA-RELATED
    MedGen: CN376852 OMIM: 620704 GeneReviews: Not available
    not available
    LEUKOENCEPHALOPATHY, PORPHYRIA-RELATED
    MedGen: CN376853 OMIM: 620711 GeneReviews: Not available
    not available

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2020-01-08)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2020-01-08)

    ClinGen Genome Curation PagePubMed

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables hydroxymethylbilane synthase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables hydroxymethylbilane synthase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    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 IBA
    Inferred from Biological aspect of Ancestor
    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 protoporphyrinogen IX biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     

    General protein information

    Preferred Names
    porphobilinogen deaminase
    Names
    porphyria, acute; Chester type
    pre-uroporphyrinogen synthase
    uroporphyrinogen I synthase
    uroporphyrinogen I synthetase
    NP_000181.2
    NP_001019553.1
    NP_001245137.1
    NP_001245138.1
    XP_005271588.1
    XP_005271589.1
    XP_005271590.1
    XP_011541098.1
    XP_016873118.1
    XP_024304228.1
    XP_054224574.1
    XP_054224575.1
    XP_054224576.1
    XP_054224577.1
    XP_054224578.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_008093.1 RefSeqGene

      Range
      5005..13673
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1076

    mRNA and Protein(s)

    1. NM_000190.4NP_000181.2  porphobilinogen deaminase isoform 1

      See identical proteins and their annotated locations for NP_000181.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AW139390, BC019323, CB128006
      Consensus CDS
      CCDS8409.1
      UniProtKB/Swiss-Prot
      A8K2L0, G3V1P4, G5EA58, P08396, P08397, Q16012
      UniProtKB/TrEMBL
      A0A3B3IRR1
      Related
      ENSP00000498786.1, ENST00000652429.1
      Conserved Domains (1) summary
      cd13645
      Location:20299
      PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
    2. NM_001024382.2NP_001019553.1  porphobilinogen deaminase isoform 2

      See identical proteins and their annotated locations for NP_001019553.1

      Status: REVIEWED

      Source sequence(s)
      AA724756, AP003391, BX647328, X04217
      Consensus CDS
      CCDS41726.1
      UniProtKB/TrEMBL
      A0A3B3IRR1
      Related
      ENSP00000376584.1, ENST00000392841.1
      Conserved Domains (1) summary
      cd13645
      Location:3282
      PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
    3. NM_001258208.2NP_001245137.1  porphobilinogen deaminase isoform 3

      See identical proteins and their annotated locations for NP_001245137.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AK131072, AW139390, CB128006
      Consensus CDS
      CCDS58186.1
      UniProtKB/TrEMBL
      A0A3B3IRR1
      Related
      ENSP00000438424.1, ENST00000544387.5
      Conserved Domains (2) summary
      PRK00072
      Location:18304
      hemC; porphobilinogen deaminase; Reviewed
      cd13645
      Location:20259
      PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
    4. NM_001258209.2NP_001245138.1  porphobilinogen deaminase isoform 4

      See identical proteins and their annotated locations for NP_001245138.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate splice junction at the 3' end of the first exon and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (4) is shorter at the N-terminus and lacks an alternate internal segment compared to isoform 1.
      Source sequence(s)
      AK000628, AP003392, AW139390, CB128006
      Consensus CDS
      CCDS58187.1
      UniProtKB/TrEMBL
      A0A3B3IRR1
      Related
      ENSP00000443058.1, ENST00000542729.5
      Conserved Domains (2) summary
      PRK00072
      Location:1287
      hemC; porphobilinogen deaminase; Reviewed
      cd13645
      Location:3242
      PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
    5. NM_001425052.1NP_001411981.1  porphobilinogen deaminase isoform 2

      Status: REVIEWED

      Source sequence(s)
      AP003391, AP003392
      UniProtKB/TrEMBL
      A0A3B3IRR1
    6. NM_001425053.1NP_001411982.1  porphobilinogen deaminase isoform 2

      Status: REVIEWED

      Source sequence(s)
      AP003391, AP003392
      UniProtKB/TrEMBL
      A0A3B3IRR1
    7. NM_001425054.1NP_001411983.1  porphobilinogen deaminase isoform 2

      Status: REVIEWED

      Source sequence(s)
      AP003391, AP003392
      UniProtKB/TrEMBL
      A0A3B3IRR1
    8. NM_001425056.1NP_001411985.1  porphobilinogen deaminase isoform 5

      Status: REVIEWED

      Source sequence(s)
      AP003391, AP003392
      UniProtKB/TrEMBL
      A0A3B3IRR1
    9. NM_001425057.1NP_001411986.1  porphobilinogen deaminase isoform 6

      Status: REVIEWED

      Source sequence(s)
      AP003391, AP003392
      UniProtKB/TrEMBL
      A0A3B3IRR1, A0A3F2YNY7
    10. NM_001425058.1NP_001411987.1  porphobilinogen deaminase isoform 7

      Status: REVIEWED

      Source sequence(s)
      AP003391, AP003392
      UniProtKB/TrEMBL
      A0A3B3IRR1
    11. NM_001425059.1NP_001411988.1  porphobilinogen deaminase isoform 8

      Status: REVIEWED

      Source sequence(s)
      AP003391, AP003392
      UniProtKB/TrEMBL
      A0A3B3IRR1
    12. NM_001425061.1NP_001411990.1  porphobilinogen deaminase isoform 9

      Status: REVIEWED

      Source sequence(s)
      AP003391, AP003392
      UniProtKB/TrEMBL
      A0A3B3IRR1
    13. NM_001425062.1NP_001411991.1  porphobilinogen deaminase isoform 10

      Status: REVIEWED

      Source sequence(s)
      AP003391, AP003392
      UniProtKB/TrEMBL
      A0A3B3IRR1, A0A8I5KXV4
    14. NM_001425063.1NP_001411992.1  porphobilinogen deaminase isoform 10

      Status: REVIEWED

      Source sequence(s)
      AP003391, AP003392
      UniProtKB/TrEMBL
      A0A3B3IRR1, A0A8I5KXV4
    15. NM_001425065.1NP_001411994.1  porphobilinogen deaminase isoform 11

      Status: REVIEWED

      Source sequence(s)
      AP003391, AP003392
      UniProtKB/TrEMBL
      A0A3B3IRR1

    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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      119084881..119093549
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005271531.2XP_005271588.1  porphobilinogen deaminase isoform X1

      Related
      ENSP00000444730.1, ENST00000537841.5
      Conserved Domains (1) summary
      cd13645
      Location:3282
      PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
    2. XM_005271532.2XP_005271589.1  porphobilinogen deaminase isoform X1

      Conserved Domains (1) summary
      cd13645
      Location:3282
      PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
    3. XM_005271533.4XP_005271590.1  porphobilinogen deaminase isoform X2

      Related
      ENSP00000445429.1, ENST00000543090.5
      Conserved Domains (1) summary
      cd13645
      Location:12281
      PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
    4. XM_024448460.2XP_024304228.1  porphobilinogen deaminase isoform X4

      Conserved Domains (1) summary
      cd13645
      Location:12241
      PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
    5. XM_017017629.2XP_016873118.1  porphobilinogen deaminase isoform X1

      UniProtKB/TrEMBL
      A0A3B3IRR1
      Related
      ENSP00000497255.1, ENST00000648374.1
      Conserved Domains (1) summary
      cd13645
      Location:3282
      PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
    6. XM_011542796.2XP_011541098.1  porphobilinogen deaminase isoform X3

      UniProtKB/TrEMBL
      A0A3B3IRR1, A0A8I5KXV4
      Related
      ENSP00000509288.1, ENST00000686218.1
      Conserved Domains (1) summary
      cd13645
      Location:1244
      PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_009646203.1 Reference GRCh38.p14 PATCHES

      Range
      106480..106757
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      119105272..119113932
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054368599.1XP_054224574.1  porphobilinogen deaminase isoform X1

    2. XM_054368601.1XP_054224576.1  porphobilinogen deaminase isoform X2

    3. XM_054368603.1XP_054224578.1  porphobilinogen deaminase isoform X4

    4. XM_054368600.1XP_054224575.1  porphobilinogen deaminase isoform X1

      UniProtKB/TrEMBL
      A0A3B3IRR1
    5. XM_054368602.1XP_054224577.1  porphobilinogen deaminase isoform X3

      UniProtKB/TrEMBL
      A0A3B3IRR1, A0A8I5KXV4