Hydroxymethylbilane Synthase (HMBS)

PBG-D; PBGD; UPS; Hydroxymethylbilane Synthase; Uroporphyrinogen I Synthase; Porphobilinogen deaminase; Pre-uroporphyrinogen synthase

SPN	S178
HGNC	4982
MGI	96112
PubMed	11857754
RGD	2801
UniProt	P08397
Wiki	HMBS

Porphobilinogen deaminase 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.

Reference

"Molecular cloning and complete primary sequence of human erythrocyte porphobilinogen deaminase."
Nucleic Acids Res. 14:5955-5968(1986) [PubMed] [Europe PMC] [Abstract]

"Tissue-specific expression of porphobilinogen deaminase. Two isoenzymes from a single gene."
Eur. J. Biochem. 162:105-110(1987) [PubMed] [Europe PMC] [Abstract]

"Hydroxymethylbilane synthase: complete genomic sequence and amplifiable polymorphisms in the human gene."
Genomics 15:21-29(1993) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Alternative transcription and splicing of the human porphobilinogen deaminase gene result either in tissue-specific or in housekeeping expression."
Proc. Natl. Acad. Sci. U.S.A. 85:6-10(1988) [PubMed] [Europe PMC] [Abstract]

"Porphobilinogen deaminase in human erythrocytes: purification of two forms with apparent molecular weights of 40 kDa and 42 kDa."
Scand. J. Clin. Lab. Invest. 49:677-684(1989) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]

"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria."
Biochem. J. 420:17-25(2009) [PubMed] [Europe PMC] [Abstract]

"Structural insight into acute intermittent porphyria."
FASEB J. 23:396-404(2009) [PubMed] [Europe PMC] [Abstract]

"Two different point G to A mutations in exon 10 of the porphobilinogen deaminase gene are responsible for acute intermittent porphyria."
J. Clin. Invest. 86:1511-1516(1990) [PubMed] [Europe PMC] [Abstract]

"Molecular heterogeneity of acute intermittent porphyria: identification of four additional mutations resulting in the CRIM-negative subtype of the disease."
Am. J. Hum. Genet. 49:421-428(1991) [PubMed] [Europe PMC] [Abstract]

"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. 51:660-665(1992) [PubMed] [Europe PMC] [Abstract]

"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. 90:12-16(1992) [PubMed] [Europe PMC] [Abstract]

"CRIM-positive mutations of acute intermittent porphyria in Finland."
Hum. Mutat. 1:392-396(1992) [PubMed] [Europe PMC] [Abstract]

"Detection of a high mutation frequency in exon 12 of the porphobilinogen deaminase gene in patients with acute intermittent porphyria."
Hum. Genet. 92:619-622(1993) [PubMed] [Europe PMC] [Abstract]

"Acute intermittent porphyria caused by an arginine to histidine substitution (R26H) in the cofactor-binding cleft of porphobilinogen deaminase."
Hum. Mol. Genet. 2:1315-1316(1993) [PubMed] [Europe PMC] [Abstract]

"Two novel mutations of the porphobilinogen deaminase gene in acute intermittent porphyria."
Hum. Mol. Genet. 2:1735-1736(1993) [PubMed] [Europe PMC] [Abstract]

"Detection of eleven mutations causing acute intermittent porphyria using denaturing gradient gel electrophoresis."
Hum. Genet. 93:47-52(1994) [PubMed] [Europe PMC] [Abstract]

"Two new mutations in the porphobilinogen deaminase gene and a screening method using PCR amplification of specific alleles."
Hum. Genet. 93:59-62(1994) [PubMed] [Europe PMC] [Abstract]

"Identification of five novel mutations in the porphobilinogen deaminase gene."
Hum. Mol. Genet. 3:809-811(1994) [PubMed] [Europe PMC] [Abstract]

"Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene."
Hum. Mutat. 4:243-252(1994) [PubMed] [Europe PMC] [Abstract]

"Acute intermittent porphyria: identification and expression of exonic mutations in the hydroxymethylbilane synthase gene. An initiation codon missense mutation in the housekeeping transcript causes 'variant acute intermittent porphyria' with normal expression of the erythroid-specific enzyme."
J. Clin. Invest. 94:1927-1937(1994) [PubMed] [Europe PMC] [Abstract]

"Acute intermittent porphyria in Finland: 19 mutations in the porphobilinogen deaminase gene."
Hum. Mol. Genet. 4:215-222(1995) [PubMed] [Europe PMC] [Abstract]

"Four mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria."
J. Med. Genet. 32:979-981(1995) [PubMed] [Europe PMC] [Abstract]

"Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria."
Am. J. Hum. Genet. 60:1373-1383(1997) [PubMed] [Europe PMC] [Abstract]

"Genetic investigation of the porphobilinogen deaminase gene in Swedish acute intermittent porphyria families."
Hum. Genet. 100:63-66(1997) [PubMed] [Europe PMC] [Abstract]

"Three splicing defects, an insertion, and two missense mutations responsible for acute intermittent porphyria."
Hum. Genet. 102:541-548(1998) [PubMed] [Europe PMC] [Abstract]

"Identification of two novel mutations in the hydroxymethylbilane synthase gene in three patients from two unrelated families with acute intermittent porphyria."
Hum. Hered. 48:24-29(1998) [PubMed] [Europe PMC] [Abstract]

"Identification and characterization of hydroxymethylbilane synthase mutations causing acute intermittent porphyria: evidence for an ancestral founder of the common G111R mutation."
Am. J. Med. Genet. 86:366-375(1999) [PubMed] [Europe PMC] [Abstract]

"Comparison of complementary and genomic DNA sequencing for the detection of mutations in the HMBS gene in British patients with acute intermittent porphyria: identification of 25 novel mutations."
Hum. Genet. 104:505-510(1999) [PubMed] [Europe PMC] [Abstract]

"Acute intermittent porphyria: characterization of two novel mutations in the porphobilinogen deaminase gene, one amino acid deletion (453-455delAGC) and one splicing acceptor site mutation (IVS8-1G>T)."
Hum. Mutat. 14:355-355(1999) [PubMed] [Europe PMC] [Abstract]

"New mutations of the hydroxymethylbilane synthase gene in German patients with acute intermittent porphyria."
Mol. Cell. Probes 13:443-447(1999) [PubMed] [Europe PMC] [Abstract]

"Identification and expression of mutations in the hydroxymethylbilane synthase gene causing acute intermittent porphyria (AIP)."
Mol. Med. 5:664-671(1999) [PubMed] [Europe PMC] [Abstract]

"Acute intermittent porphyria: novel missense mutations in the human hydroxymethylbilane synthase gene."
Genet. Med. 2:290-295(2000) [PubMed] [Europe PMC] [Abstract]

"Porphobilinogen deaminase gene in African and Afro-Caribbean ethnic groups: mutations causing acute intermittent porphyria and specific intragenic polymorphisms."
Hum. Genet. 107:150-159(2000) [PubMed] [Europe PMC] [Abstract]

"Identification of a prevalent nonsense mutation (W283X) and two novel mutations in the porphobilinogen deaminase gene of Swiss patients with acute intermittent porphyria."
Hum. Hered. 50:247-250(2000) [PubMed] [Europe PMC] [Abstract]

"Identification and characterization of two novel mutations that produce acute intermittent porphyria: a 3-base deletion (841-843delGGA) and a missense mutation (T35M)."
Hum. Mutat. 16:373-373(2000) [PubMed] [Europe PMC] [Abstract]

Erratum
Hum. Genet. 109:241-241(2001)

"Molecular and biochemical studies of acute intermittent porphyria in 196 patients and their families."
Clin. Chem. 48:1891-1900(2002) [PubMed] [Europe PMC] [Abstract]

"Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene."
Clin. Genet. 62:288-297(2002) [PubMed] [Europe PMC] [Abstract]

"Molecular study of the hydroxymethylbilane synthase gene (HMBS) among Polish patients with acute intermittent porphyria."
Hum. Mutat. 19:310-310(2002) [PubMed] [Europe PMC] [Abstract]

"Modulation of penetrance by the wild-type allele in dominantly inherited erythropoietic protoporphyria and acute hepatic porphyrias."
Hum. Genet. 114:256-262(2004) [PubMed] [Europe PMC] [Abstract]

"Homozygous acute intermittent porphyria in a 7-year-old boy with massive excretions of porphyrins and porphyrin precursors."
J. Inherit. Metab. Dis. 27:19-27(2004) [PubMed] [Europe PMC] [Abstract]

"Mutation hotspots in the human porphobilinogen deaminase gene: recurrent mutations G111R and R173Q occurring at CpG motifs."
J. Inherit. Metab. Dis. 27:625-631(2004) [PubMed] [Europe PMC] [Abstract]