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Genetics Home Reference: your guide to understanding genetic conditions
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HLCS

Reviewed June 2007

What is the official name of the HLCS gene?

The official name of this gene is “holocarboxylase synthetase (biotin-(proprionyl-CoA-carboxylase (ATP-hydrolysing)) ligase).”

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

What is the normal function of the HLCS gene?

The HLCS gene provides instructions for making an enzyme called holocarboxylase synthetase. This enzyme is important for the effective use of biotin, a B vitamin found in foods such as liver, egg yolks, and milk. In many of the body's tissues, holocarboxylase synthetase activates enzymes called biotin-dependent carboxylases by attaching biotin to them. These carboxylases are involved in many critical cellular functions, including the production and breakdown of proteins, fats, and carbohydrates.

Holocarboxylase synthetase may also play a role in regulating the activity of genes. In the nucleus, the enzyme likely attaches biotin molecules to histones, which are structural proteins that bind to DNA and give chromosomes their shape. Changing the shape of histones may help determine whether certain genes are turned on or off; however, it is not known how adding biotin affects gene regulation.

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

holocarboxylase synthetase deficiency - caused by mutations in the HLCS gene

About 30 mutations in the HLCS gene have been identified in people with holocarboxylase synthetase deficiency. Most of these mutations change a single protein building block (amino acid) in the holocarboxylase synthetase enzyme. Many of the known mutations occur in a region of the enzyme that binds to biotin. These genetic changes reduce the enzyme's ability to attach biotin to carboxylases and histones. Without biotin, carboxylases remain inactive and are unable to process proteins, fats, and carbohydrates effectively. A lack of holocarboxylase synthetase activity may also alter the regulation of certain genes that are important for normal development. Researchers believe that these defects in enzyme function underlie the breathing problems, skin rashes, and other characteristic signs and symptoms of holocarboxylase synthetase deficiency.

Where is the HLCS gene located?

Cytogenetic Location: 21q22.13

Molecular Location on chromosome 21: base pairs 36,750,887 to 36,990,244

The HLCS gene is located on the long (q) arm of chromosome 21 at position 22.13.

The HLCS gene is located on the long (q) arm of chromosome 21 at position 22.13.

More precisely, the HLCS gene is located from base pair 36,750,887 to base pair 36,990,244 on chromosome 21.

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 HLCS?

You and your healthcare professional may find the following resources about HLCS 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 HLCS gene or gene products?

  • biotin apo-protein ligase
  • biotin-protein ligase
  • BPL1_HUMAN
  • HCS
  • holocarboxylase synthetase
  • holocarboxylase synthetase (biotin-(proprionyl-Coenzyme A-carboxylase (ATP-hydrolysing)) ligase)

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 HLCS?

amino acid ; ATP ; biotin ; breakdown ; carboxylase ; CoA ; coenzyme A ; deficiency ; DNA ; egg ; enzyme ; gene ; gene regulation ; ligase ; nucleus ; protein

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

References

  • Dupuis L, Campeau E, Leclerc D, Gravel RA. Mechanism of biotin responsiveness in biotin-responsive multiple carboxylase deficiency. Mol Genet Metab. 1999 Feb;66(2):80-90. (http://www.ncbi.nlm.nih.gov/pubmed/10068510?dopt=Abstract)
  • Gravel RA, Narang MA. Molecular genetics of biotin metabolism: old vitamin, new science. J Nutr Biochem. 2005 Jul;16(7):428-31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15992684?dopt=Abstract)
  • Morrone A, Malvagia S, Donati MA, Funghini S, Ciani F, Pela I, Boneh A, Peters H, Pasquini E, Zammarchi E. Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency. Am J Med Genet. 2002 Jul 22;111(1):10-8. (http://www.ncbi.nlm.nih.gov/pubmed/12124727?dopt=Abstract)
  • Narang MA, Dumas R, Ayer LM, Gravel RA. Reduced histone biotinylation in multiple carboxylase deficiency patients: a nuclear role for holocarboxylase synthetase. Hum Mol Genet. 2004 Jan 1;13(1):15-23. Epub 2003 Nov 12. (http://www.ncbi.nlm.nih.gov/pubmed/14613969?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3141)
  • Pacheco-Alvarez D, Solórzano-Vargas RS, Gravel RA, Cervantes-Roldán R, Velázquez A, León-Del-Río A. Paradoxical regulation of biotin utilization in brain and liver and implications for inherited multiple carboxylase deficiency. J Biol Chem. 2004 Dec 10;279(50):52312-8. Epub 2004 Sep 28. (http://www.ncbi.nlm.nih.gov/pubmed/15456772?dopt=Abstract)
  • Suzuki Y, Yang X, Aoki Y, Kure S, Matsubara Y. Mutations in the holocarboxylase synthetase gene HLCS. Hum Mutat. 2005 Oct;26(4):285-90. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16134170?dopt=Abstract)
  • Tang NL, Hui J, Yong CK, Wong LT, Applegarth DA, Vallance HD, Law LK, Fung SL, Mak TW, Sung YM, Cheung KL, Fok TF. A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency. Clin Biochem. 2003 Mar;36(2):145-9. (http://www.ncbi.nlm.nih.gov/pubmed/12633764?dopt=Abstract)
  • Yang X, Aoki Y, Li X, Sakamoto O, Hiratsuka M, Kure S, Taheri S, Christensen E, Inui K, Kubota M, Ohira M, Ohki M, Kudoh J, Kawasaki K, Shibuya K, Shintani A, Asakawa S, Minoshima S, Shimizu N, Narisawa K, Matsubara Y, Suzuki Y. Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency. Hum Genet. 2001 Nov;109(5):526-34. Epub 2001 Oct 5. (http://www.ncbi.nlm.nih.gov/pubmed/11735028?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: June 2007
Published: August 18, 2014