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Normal Function
The HMBS gene provides instructions for making an enzyme known as hydroxymethylbilane synthase. This enzyme is involved in the production of a molecule called heme. Heme is vital for all of the body's organs, although it is most abundant in the blood, bone marrow, and liver. Heme is an essential component of iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood).
The production of heme is a multi-step process that requires eight different enzymes. Hydroxymethylbilane synthase is responsible for the third step in this process, which combines four molecules of porphobilinogen (the product of the second step) to form a compound called hydroxymethylbilane. In subsequent steps, five other enzymes produce and modify compounds that ultimately lead to heme.
Health Conditions Related to Genetic Changes
Porphyria
More than 300 mutations in the HMBS gene have been identified in people with a form of porphyria known as acute intermittent porphyria. Some of these mutations change single protein building blocks (amino acids) in hydroxymethylbilane synthase. Other mutations add or delete genetic material within the HMBS gene, which alters the structure and function of the enzyme.
Mutations in the HMBS gene reduce the activity of hydroxymethylbilane synthase, allowing compounds called porphyrins to build up in the liver and other organs. These compounds are formed during the normal process of heme production, but reduced activity of hydroxymethylbilane synthase allows them to accumulate to toxic levels. This buildup, in combination with nongenetic factors such as certain drugs, alcohol, smoking, and dieting, leads to attacks of severe abdominal pain and other symptoms in people with acute intermittent porphyria.
More About This Health ConditionOther Names for This Gene
- HEM3_HUMAN
- Hydroxymethylbilane Synthetase
- PBG-D
- PBGD
- Porphobilinogen Ammonia-Lyase
- Porphobilinogen ammonia-lyase (polymerizing)
- Porphobilinogen Deaminase
- Porphyrinogen Synthetase
- Pre-uroporphyrinogen synthase
- Preuroporphyrinogen Synthetase
- UPS
- Uroporphyrinogen synthase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Badminton MN, Elder GH. Molecular mechanisms of dominant expression in porphyria. J Inherit Metab Dis. 2005;28(3):277-86. doi: 10.1007/s10545-005-8050-3. Citation on PubMed
- Elder GH. Genetic defects in the porphyrias: types and significance. Clin Dermatol. 1998 Mar-Apr;16(2):225-33. doi: 10.1016/s0738-081x(97)00202-2. No abstract available. Citation on PubMed
- Hrdinka M, Puy H, Martasek P. May 2006 update in porphobilinogen deaminase gene polymorphisms and mutations causing acute intermittent porphyria: comparison with the situation in Slavic population. Physiol Res. 2006;55 Suppl 2:S119-136. doi: 10.33549/physiolres.930000.55.S2.119. Citation on PubMed
- Kauppinen R. Porphyrias. Lancet. 2005 Jan 15-21;365(9455):241-52. doi: 10.1016/S0140-6736(05)17744-7. Citation on PubMed
- Sassa S, Kappas A. Molecular aspects of the inherited porphyrias. J Intern Med. 2000 Feb;247(2):169-78. doi: 10.1046/j.1365-2796.2000.00618.x. Citation on PubMed
- Tjensvoll K, Bruland O, Floderus Y, Skadberg O, Sandberg S, Apold J. Haplotype analysis of Norwegian and Swedish patients with acute intermittent porphyria (AIP): Extreme haplotype heterogeneity for the mutation R116W. Dis Markers. 2003-2004;19(1):41-6. doi: 10.1155/2003/384971. Citation on PubMed or Free article on PubMed Central
- Whatley SD, Roberts AG, Llewellyn DH, Bennett CP, Garrett C, Elder GH. Non-erythroid form of acute intermittent porphyria caused by promoter and frameshift mutations distant from the coding sequence of exon 1 of the HMBS gene. Hum Genet. 2000 Sep;107(3):243-8. doi: 10.1007/s004390000356. Citation on PubMed
- Yang CC, Kuo HC, You HL, Wang J, Huang CC, Liu CY, Lan MY, Stephenson DA, Lee MJ. HMBS mutations in Chinese patients with acute intermittent porphyria. Ann Hum Genet. 2008 Sep;72(Pt 5):683-6. doi: 10.1111/j.1469-1809.2008.00463.x. Citation on PubMed
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