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Genetics Home Reference: your guide to understanding genetic conditions
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HMBS

Reviewed July 2009

What is the official name of the HMBS gene?

The official name of this gene is “hydroxymethylbilane synthase.”

HMBS is the gene's official symbol. The HMBS gene is also known by other names, listed below.

What is the normal function of the HMBS gene?

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.

How are changes in the HMBS gene related to health conditions?

porphyria - caused by mutations in the HMBS gene

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.

Where is the HMBS gene located?

Cytogenetic Location: 11q23.3

Molecular Location on chromosome 11: base pairs 119,084,876 to 119,093,548

The HMBS gene is located on the long (q) arm of chromosome 11 at position 23.3.

The HMBS gene is located on the long (q) arm of chromosome 11 at position 23.3.

More precisely, the HMBS gene is located from base pair 119,084,876 to base pair 119,093,548 on chromosome 11.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about HMBS?

You and your healthcare professional may find the following resources about HMBS helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the HMBS gene or gene products?

  • HEM3_HUMAN
  • Hydroxymethylbilane Synthetase
  • PBGD
  • PBG-D
  • Porphobilinogen Ammonia-Lyase
  • Porphobilinogen ammonia-lyase (polymerizing)
  • Porphobilinogen Deaminase
  • Porphyrinogen Synthetase
  • Pre-uroporphyrinogen synthase
  • Preuroporphyrinogen Synthetase
  • UPS
  • Uroporphyrinogen synthase

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding HMBS?

acids ; acute ; ammonia ; bone marrow ; compound ; enzyme ; gene ; heme ; hemoglobin ; iron ; molecule ; oxygen ; protein ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Badminton MN, Elder GH. Molecular mechanisms of dominant expression in porphyria. J Inherit Metab Dis. 2005;28(3):277-86. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15868463?dopt=Abstract)
  • Elder GH. Genetic defects in the porphyrias: types and significance. Clin Dermatol. 1998 Mar-Apr;16(2):225-33. Review. (http://www.ncbi.nlm.nih.gov/pubmed/9554235?dopt=Abstract)
  • 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:S119-36. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17298216?dopt=Abstract)
  • Kauppinen R. Porphyrias. Lancet. 2005 Jan 15-21;365(9455):241-52. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15652607?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3145)
  • Sassa S, Kappas A. Molecular aspects of the inherited porphyrias. J Intern Med. 2000 Feb;247(2):169-78. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10692079?dopt=Abstract)
  • Tjensvoll K, Bruland O, Floderus Y, Skadberg Ø, 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. (http://www.ncbi.nlm.nih.gov/pubmed/14757946?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/11071386?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18627369?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: July 2009
Published: August 25, 2014