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Aliases for HMBS Gene

Aliases for HMBS Gene

  • Hydroxymethylbilane Synthase 2 3 4 5
  • Porphyria, Acute; Chester Type 2 3
  • Pre-Uroporphyrinogen Synthase 3 4
  • Uroporphyrinogen I Synthase 2 3
  • EC 4 63
  • PBG-D 3 4
  • PBGD 3 4
  • UPS 3 4
  • Uroporphyrinogen I Synthetase 3
  • Porphobilinogen Deaminase 2
  • PORC 3

External Ids for HMBS Gene

Previous HGNC Symbols for HMBS Gene

  • PBGD
  • UPS
  • PORC

Previous GeneCards Identifiers for HMBS Gene

  • GC11P135563
  • GC11P120467
  • GC11P118989
  • GC11P118493
  • GC11P118460
  • GC11P118955
  • GC11P114895

Summaries for HMBS Gene

Entrez Gene Summary for HMBS Gene

  • 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]

GeneCards Summary for HMBS Gene

HMBS (Hydroxymethylbilane Synthase) is a Protein Coding gene. Diseases associated with HMBS include Porphyria, Acute Intermittent and Focal Dermal Hypoplasia. Among its related pathways are Porphyrin and chlorophyll metabolism and Metabolism. GO annotations related to this gene include hydroxymethylbilane synthase activity.

UniProtKB/Swiss-Prot for HMBS Gene

  • Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps.

Gene Wiki entry for HMBS Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HMBS Gene

Genomics for HMBS Gene

Regulatory Elements for HMBS Gene

Enhancers for HMBS Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around HMBS on UCSC Golden Path with GeneCards custom track

Promoters for HMBS Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around HMBS on UCSC Golden Path with GeneCards custom track

Genomic Location for HMBS Gene

119,084,866 bp from pter
119,093,549 bp from pter
8,684 bases
Plus strand

Genomic View for HMBS Gene

Genes around HMBS on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HMBS Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HMBS Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HMBS Gene

Proteins for HMBS Gene

  • Protein details for HMBS Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Porphobilinogen deaminase
    Protein Accession:
    Secondary Accessions:
    • A8K2L0
    • G3V1P4
    • G5EA58
    • P08396
    • Q16012

    Protein attributes for HMBS Gene

    361 amino acids
    Molecular mass:
    39330 Da
    Name=dipyrromethane; Xref=ChEBI:CHEBI:60342;
    Quaternary structure:
    No Data Available
    • The porphobilinogen subunits are added to the dipyrromethane group.

    Three dimensional structures from OCA and Proteopedia for HMBS Gene

    Alternative splice isoforms for HMBS Gene


neXtProt entry for HMBS Gene

Proteomics data for HMBS Gene at MOPED

Selected DME Specific Peptides for HMBS Gene

Post-translational modifications for HMBS Gene

  • Ubiquitination at Lys 227
  • Modification sites at PhosphoSitePlus

Domains & Families for HMBS Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the HMBS family.
  • Belongs to the HMBS family.
genes like me logo Genes that share domains with HMBS: view

No data available for Gene Families for HMBS Gene

Function for HMBS Gene

Molecular function for HMBS Gene

GENATLAS Biochemistry:
hydroxymethylbilane synthase,cytosolic,catalyzing the polymerization of four PGB,third step of porphyrin biosynthesis
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=48 uM for porphobilinogen {ECO:0000269 PubMed:23815679}; Vmax=1261 nmol/h/mg enzyme (at 37 degrees Celsius) {ECO:0000269 PubMed:23815679}; Temperature dependence: Displays high thermal stability. The half-denaturation temperature (Tm) is about 74 degrees Celsius. {ECO:0000269 PubMed:23815679};
UniProtKB/Swiss-Prot CatalyticActivity:
4 porphobilinogen + H(2)O = hydroxymethylbilane + 4 NH(3).
UniProtKB/Swiss-Prot Function:
Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps.

Enzyme Numbers (IUBMB) for HMBS Gene

Gene Ontology (GO) - Molecular Function for HMBS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004852 uroporphyrinogen-III synthase activity IEA --
genes like me logo Genes that share ontologies with HMBS: view
genes like me logo Genes that share phenotypes with HMBS: view

Human Phenotype Ontology for HMBS Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HMBS Gene

MGI Knock Outs for HMBS:

Animal Model Products

miRNA for HMBS Gene

miRTarBase miRNAs that target HMBS

No data available for Transcription Factor Targets and HOMER Transcription for HMBS Gene

Localization for HMBS Gene

Subcellular locations from UniProtKB/Swiss-Prot for HMBS Gene


No data available for Subcellular locations from COMPARTMENTS and Gene Ontology (GO) - Cellular Components for HMBS Gene

Pathways & Interactions for HMBS Gene

genes like me logo Genes that share pathways with HMBS: view

Pathways by source for HMBS Gene

UniProtKB/Swiss-Prot P08397-HEM3_HUMAN

  • Pathway: Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 2/4.

Interacting Proteins for HMBS Gene

Gene Ontology (GO) - Biological Process for HMBS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006778 porphyrin-containing compound metabolic process TAS --
GO:0006782 protoporphyrinogen IX biosynthetic process IEA --
GO:0009743 response to carbohydrate IEA --
GO:0010043 response to zinc ion IEA --
GO:0010288 response to lead ion IEA --
genes like me logo Genes that share ontologies with HMBS: view

No data available for SIGNOR curated interactions for HMBS Gene

Drugs & Compounds for HMBS Gene

(19) Drugs for HMBS Gene - From: DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Porphobilinogen Experimental Pharma 0
RAAV5-PBGD Pharma 0
heme Pharma Agonist 0

(21) Additional Compounds for HMBS Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • 3,8,13,18-Tetrakis(carboxymethyl)-19-(hydroxymethyl)bilane-2,7,12,17-tetrapropanoate
  • 3,8,13,18-Tetrakis(carboxymethyl)-19-(hydroxymethyl)bilane-2,7,12,17-tetrapropanoic acid
  • 3,8,13,18-Tetrakis(carboxymethyl)-5,10,15,22,23,24-hexahydro-19-(hydroxymethyl)-21H-Biline-2,7,12,17-tetrapropanoate
  • 3,8,13,18-Tetrakis(carboxymethyl)-5,10,15,22,23,24-hexahydro-19-(hydroxymethyl)-21H-Biline-2,7,12,17-tetrapropanoic acid
  • 3-[2-[[4-(2-Carboxyethyl)-5-[[4-(2-carboxyethyl)-5-[[4-(2-carboxyethyl)-3-(carboxymethyl)-1H-pyrrol-2-yl]methyl]-3-(carboxymethyl)-1H-pyrrol-2-yl]methyl]-3-(carboxymethyl)-1H-pyrrol-2-yl]methyl]-4-(carboxymethyl)-5-(hydroxymethyl)-1H-pyrrol-3-yl]propanoate
  • Ammonia anhydrous
  • Ammonia inhalant
  • Ammonia solution strong [usan]
  • Ammonia water
  • Ammoniak
  • Formyl coenzyme A
  • Dihydrogen oxide
  • Steam
genes like me logo Genes that share compounds with HMBS: view

Transcripts for HMBS Gene

Unigene Clusters for HMBS Gene

Hydroxymethylbilane synthase:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for HMBS Gene

No ASD Table

Relevant External Links for HMBS Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for HMBS Gene

mRNA expression in normal human tissues for HMBS Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HMBS Gene

This gene is overexpressed in Whole Blood (x5.1).

Protein differential expression in normal tissues from HIPED for HMBS Gene

This gene is overexpressed in Fetal Liver (25.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for HMBS Gene

SOURCE GeneReport for Unigene cluster for HMBS Gene Hs.82609

mRNA Expression by UniProt/SwissProt for HMBS Gene

Tissue specificity: Isoform 1 is ubiquitously expressed. Isoform 2 is found only in erythroid cells.
genes like me logo Genes that share expression patterns with HMBS: view

Protein tissue co-expression partners for HMBS Gene

Primer Products

Orthologs for HMBS Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for HMBS Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia HMBS 35
  • 90.3 (n)
  • 92.8 (a)
  • 93 (a)
(Canis familiaris)
Mammalia HMBS 35
  • 90.4 (n)
  • 94.18 (a)
  • 94 (a)
(Mus musculus)
Mammalia Hmbs 35
  • 87.37 (n)
  • 91.36 (a)
Hmbs 16
Hmbs 36
  • 91 (a)
(Rattus norvegicus)
Mammalia Hmbs 35
  • 87.74 (n)
  • 91.36 (a)
(Monodelphis domestica)
Mammalia HMBS 36
  • 85 (a)
(Ornithorhynchus anatinus)
Mammalia HMBS 36
  • 77 (a)
(Pan troglodytes)
Mammalia HMBS 36
  • 100 (a)
(Gallus gallus)
Aves HMBS 35
  • 70.79 (n)
  • 76.44 (a)
  • 74 (a)
(Anolis carolinensis)
Reptilia HMBS 36
  • 72 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia hmbs 35
  • 67.82 (n)
  • 74.43 (a)
Str.4847 35
African clawed frog
(Xenopus laevis)
Amphibia Xl.32592 35
(Danio rerio)
Actinopterygii hmbsb 35
  • 67.83 (n)
  • 74.05 (a)
zgc64128 35
hmbsa 36
  • 66 (a)
hmbsb 36
  • 69 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP011080 35
  • 56.2 (n)
  • 56.93 (a)
fruit fly
(Drosophila melanogaster)
Insecta l(3)02640 35
  • 56.29 (n)
  • 54.9 (a)
l(3)02640 36
  • 26 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ABL107C 35
  • 51.68 (n)
  • 45.6 (a)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0C15147g 35
  • 48.21 (n)
  • 43.32 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes HEM3 35
  • 51.03 (n)
  • 43.32 (a)
HEM3 36
  • 41 (a)
HEM3 38
thale cress
(Arabidopsis thaliana)
eudicotyledons HEMC 35
  • 45.4 (n)
  • 40.34 (a)
(Oryza sativa)
Liliopsida Os02g0168800 35
  • 46.53 (n)
  • 40.99 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.12172 35
bread mold
(Neurospora crassa)
Ascomycetes NCU10292 35
  • 51.8 (n)
  • 45.86 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes hem3 35
  • 48.75 (n)
  • 45.31 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.10281 36
  • 55 (a)
Species with no ortholog for HMBS:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for HMBS Gene

Gene Tree for HMBS (if available)
Gene Tree for HMBS (if available)

Paralogs for HMBS Gene

genes like me logo Genes that share paralogs with HMBS: view

No data available for Paralogs for HMBS Gene

Variants for HMBS Gene

Sequence variations from dbSNP and Humsavar for HMBS Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
VAR_003638 Acute intermittent porphyria (AIP)
VAR_003639 Acute intermittent porphyria (AIP)
VAR_003640 Acute intermittent porphyria (AIP)
VAR_003641 Acute intermittent porphyria (AIP)
VAR_003642 Acute intermittent porphyria (AIP)

Structural Variations from Database of Genomic Variants (DGV) for HMBS Gene

Variant ID Type Subtype PubMed ID
nsv898416 CNV Loss 21882294

Variation tolerance for HMBS Gene

Residual Variation Intolerance Score: 38% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.79; 16.67% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HMBS Gene

Human Gene Mutation Database (HGMD)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HMBS Gene

Disorders for HMBS Gene

MalaCards: The human disease database

(12) MalaCards diseases for HMBS Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
porphyria, acute intermittent
  • porphyria, acute intermittent, nonerythroid variant
focal dermal hypoplasia
  • basal cell nevus syndrome
  • disorder of porphyrin and hem metabolism
  • harderoporphyria
acute porphyria
  • hepatic porphyria
- elite association - COSMIC cancer census association via MalaCards
Search HMBS in MalaCards View complete list of genes associated with diseases


  • Acute intermittent porphyria (AIP) [MIM:176000]: 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. AIP is an autosomal dominant form of hepatic porphyria characterized by attacks of gastrointestinal disturbances, abdominal colic, with neurological dysfunctions, hypertension, tachycardia and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. {ECO:0000269 PubMed:10453740, ECO:0000269 PubMed:10494093, ECO:0000269 PubMed:10502788, ECO:0000269 PubMed:10602775, ECO:0000269 PubMed:10657149, ECO:0000269 PubMed:10782018, ECO:0000269 PubMed:11013452, ECO:0000269 PubMed:11030413, ECO:0000269 PubMed:11399210, ECO:0000269 PubMed:11857754, ECO:0000269 PubMed:12372055, ECO:0000269 PubMed:12406973, ECO:0000269 PubMed:12773194, ECO:0000269 PubMed:1301948, ECO:0000269 PubMed:1427766, ECO:0000269 PubMed:14669009, ECO:0000269 PubMed:14757946, ECO:0000269 PubMed:1496994, ECO:0000269 PubMed:14970743, ECO:0000269 PubMed:15669678, ECO:0000269 PubMed:16211556, ECO:0000269 PubMed:1714233, ECO:0000269 PubMed:18406650, ECO:0000269 PubMed:19138865, ECO:0000269 PubMed:19292878, ECO:0000269 PubMed:2243128, ECO:0000269 PubMed:23815679, ECO:0000269 PubMed:25703257, ECO:0000269 PubMed:25870942, ECO:0000269 PubMed:7757070, ECO:0000269 PubMed:7962538, ECO:0000269 PubMed:8081367, ECO:0000269 PubMed:8262523, ECO:0000269 PubMed:8268934, ECO:0000269 PubMed:8270254, ECO:0000269 PubMed:8270256, ECO:0000269 PubMed:8401516, ECO:0000269 PubMed:8825929, ECO:0000269 PubMed:9199558, ECO:0000269 PubMed:9225970, ECO:0000269 PubMed:9463797, ECO:0000269 PubMed:9654202, ECO:0000269 Ref.45}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for HMBS Gene

porphyria,acute,intermittent (AIP),including an erythroid form and a non-erythroid variant

Relevant External Links for HMBS

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with HMBS: view

Publications for HMBS Gene

  1. Molecular study of the hydroxymethylbilane synthase gene (HMBS) among Polish patients with acute intermittent porphyria. (PMID: 11857754) Gregor A. … Minder E.I. (Hum. Mutat. 2002) 3 4 23 67
  2. Structural insight into acute intermittent porphyria. (PMID: 18936296) Song G. … Liu Z.J. (FASEB J. 2009) 3 23
  3. Correlation between biochemical findings, structural and enzymatic abnormalities in mutated HMBS identified in six Israeli families with acute intermittent porphyria. (PMID: 19138865) Ulbrichova D. … Schoenfeld N. (Blood Cells Mol. Dis. 2009) 3 23
  4. Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria. (PMID: 19207107) Gill R. … Shoolingin-Jordan P.M. (Biochem. J. 2009) 3 23
  5. Acute intermittent porphyria--impact of mutations found in the hydroxymethylbilane synthase gene on biochemical and enzymatic protein properties. (PMID: 19292878) Ulbrichova D. … Martasek P. (FEBS J. 2009) 3 23

Products for HMBS Gene

Sources for HMBS Gene