Porphobilinogen deaminase

Hydroxymethylbilane synthase
Identifiers
Symbols	HMBS ; PBG-D; PBGD; UPS
External IDs	Template:OMIM5 Template:MGI HomoloGene: 158
EC number	2.5.1.61
Gene ontology Molecular function Template:GNF GO Template:GNF GO Biological process Template:GNF GO
RNA expression pattern
File:PBB GE HMBS 203040 s at tn.png
File:PBB GE HMBS 213344 s at tn.png
File:PBB GE HMBS 212524 x at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

Porphobilinogen deaminase (or hydroxymethylbilane synthase) is an enzyme involved in the third step of the metabolism of porphyrin, converting porphobilinogen into hydroxymethyl bilane. The enzyme has the unique cofactor dipyrromethane. Defective activity of this enzyme can lead to the disorder Acute intermittent porphyria.

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.

Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)

Older sources categorize it under EC 4.3.1.8.

Further reading

• Deybach JC, Puy H (1995). "Porphobilinogen deaminase gene structure and molecular defects". J. Bioenerg. Biomembr. 27 (2): 197–205. PMID 7592566.
• Astrin KH, Desnick RJ (1995). "Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene". Hum. Mutat. 4 (4): 243–52. doi:10.1002/humu.1380040403. PMID 7866402.
• Helliwell JR, Nieh YP, Habash J; et al. (2003). "Time-resolved and static-ensemble structural chemistry of hydroxymethylbilane synthase". Faraday Discuss. 122: 131–44, discussion 171-90. PMID 12555854.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Hessels J, Voortman G, van der Wagen A; et al. (2004). "Homozygous acute intermittent porphyria in a 7-year-old boy with massive excretions of porphyrins and porphyrin precursors". J. Inherit. Metab. Dis. 27 (1): 19–27. doi:10.1023/B:BOLI.0000016613.75677.05. PMID 14970743.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Kauppinen R (2004). "Molecular diagnostics of acute intermittent porphyria". Expert Rev. Mol. Diagn. 4 (2): 243–9. doi:10.1586/14737159.4.2.243. PMID 14995910.
• Hrdinka M, Puy H, Martasek P (2007). "May 2006 update in porphobilinogen deaminase gene polymorphisms and mutations causing acute intermittent porphyria: comparison with the situation in Slavic population". Physiological research / Academia Scientiarum Bohemoslovaca. 55 Suppl 2: S119–36. PMID 17298216.CS1 maint: Multiple names: authors list (link)
• Kauppinen R, Peltonen L, Pihlaja H, Mustajoki P (1993). "CRIM-positive mutations of acute intermittent porphyria in Finland". Hum. Mutat. 1 (5): 392–6. doi:10.1002/humu.1380010508. PMID 1301948.CS1 maint: Multiple names: authors list (link)
• Mgone CS, Lanyon WG, Moore MR, Connor JM (1992). "Detection of seven point mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria, by direct sequencing of in vitro amplified cDNA". Hum. Genet. 90 (1–2): 12–6. PMID 1427766.CS1 maint: Multiple names: authors list (link)
• Gu XF, de Rooij F, Voortman G; et al. (1992). "High frequency of mutations in exon 10 of the porphobilinogen deaminase gene in patients with a CRIM-positive subtype of acute intermittent porphyria". Am. J. Hum. Genet. 51 (3): 660–5. PMID 1496994.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Delfau MH, Picat C, De Rooij F; et al. (1991). "Molecular heterogeneity of acute intermittent porphyria: identification of four additional mutations resulting in the CRIM-negative subtype of the disease". Am. J. Hum. Genet. 49 (2): 421–8. PMID 1714233.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Namba H, Narahara K, Tsuji K; et al. (1991). "Assignment of human porphobilinogen deaminase to 11q24.1----q24.2 by in situ hybridization and gene dosage studies". Cytogenet. Cell Genet. 57 (2–3): 105–8. PMID 1914516.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Lee JS, Anvret M (1992). "Identification of the most common mutation within the porphobilinogen deaminase gene in Swedish patients with acute intermittent porphyria". Proc. Natl. Acad. Sci. U.S.A. 88 (23): 10912–5. PMID 1961762.
• Tunnacliffe A, McGuire RS (1991). "A physical linkage group in human chromosome band 11q23 covering a region implicated in leukocyte neoplasia". Genomics. 8 (3): 447–53. PMID 1981047.
• Lander M, Pitt AR, Alefounder PR; et al. (1991). "Studies on the mechanism of hydroxymethylbilane synthase concerning the role of arginine residues in substrate binding". Biochem. J. 275 ( Pt 2): 447–52. PMID 2025226.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Scobie GA, Llewellyn DH, Urquhart AJ; et al. (1990). "Acute intermittent porphyria caused by a C----T mutation that produces a stop codon in the porphobilinogen deaminase gene". Hum. Genet. 85 (6): 631–4. PMID 2227955.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Delfau MH, Picat C, de Rooij FW; et al. (1990). "Two different point G to A mutations in exon 10 of the porphobilinogen deaminase gene are responsible for acute intermittent porphyria". J. Clin. Invest. 86 (5): 1511–6. PMID 2243128.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Lannfelt L, Wetterberg L, Lilius L; et al. (1990). "Porphobilinogen deaminase in human erythrocytes: purification of two forms with apparent molecular weights of 40 kDa and 42 kDa". Scand. J. Clin. Lab. Invest. 49 (7): 677–84. PMID 2609111.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Grandchamp B, Picat C, de Rooij F; et al. (1989). "A point mutation G----A in exon 12 of the porphobilinogen deaminase gene results in exon skipping and is responsible for acute intermittent porphyria". Nucleic Acids Res. 17 (16): 6637–49. PMID 2789372.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Raich N, Romeo PH, Dubart A; et al. (1986). "Molecular cloning and complete primary sequence of human erythrocyte porphobilinogen deaminase". Nucleic Acids Res. 14 (15): 5955–68. PMID 2875434.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Vidaud M, Gattoni R, Stevenin J; et al. (1989). "A 5' splice-region G----C mutation in exon 1 of the human beta-globin gene inhibits pre-mRNA splicing: a mechanism for beta+-thalassemia". Proc. Natl. Acad. Sci. U.S.A. 86 (3): 1041–5. PMID 2915972.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)