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Genetics Home Reference: your guide to understanding genetic conditions
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HMGCL

Reviewed October 2008

What is the official name of the HMGCL gene?

The official name of this gene is “3-hydroxymethyl-3-methylglutaryl-CoA lyase.”

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

What is the normal function of the HMGCL gene?

The HMGCL gene provides instructions for making an enzyme called 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMG-CoA lyase). This enzyme is found in mitochondria, which are the energy-producing centers inside cells. HMG-CoA lyase plays a critical role in breaking down proteins and fats from the diet. Specifically, it is responsible for processing leucine, a protein building block (amino acid) that is part of many proteins. HMG-CoA lyase also produces ketones during the breakdown of fats. Ketones are compounds that certain organs and tissues, particularly the brain, use for energy when the simple sugar glucose is not available. For example, ketones are important sources of energy during periods of fasting.

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

3-hydroxy-3-methylglutaryl-CoA lyase deficiency - caused by mutations in the HMGCL gene

More than 25 mutations in the HMGCL gene have been identified in people with 3-hydroxymethyl-3-methylglutaryl-CoA lyase deficiency (also called HMG-CoA lyase deficiency). Most of these mutations change single amino acids in the HMG-CoA lyase enzyme. For example, the most common mutation in the Saudi Arabian population replaces the amino acid arginine with the amino acid glutamine at position 41 (written as Arg41Gln or R41Q). Other HMGCL mutations result in the production of an abnormally short enzyme that is missing critical segments.

If a mutation reduces or eliminates the activity of HMG-CoA lyase, the body is unable to process leucine or make ketones properly. When leucine is not processed normally, chemical byproducts called organic acids can build up and make the blood too acidic (metabolic acidosis). A shortage of ketones can cause blood sugar levels to become dangerously low (hypoglycemia). The effects of metabolic acidosis and hypoglycemia can damage cells, particularly in the brain, resulting in serious illness in children with HMG-CoA lyase deficiency.

Where is the HMGCL gene located?

Cytogenetic Location: 1p36.1-p35

Molecular Location on chromosome 1: base pairs 23,801,876 to 23,825,458

The HMGCL gene is located on the short (p) arm of chromosome 1 between positions 36.1 and 35.

The HMGCL gene is located on the short (p) arm of chromosome 1 between positions 36.1 and 35.

More precisely, the HMGCL gene is located from base pair 23,801,876 to base pair 23,825,458 on chromosome 1.

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 HMGCL?

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

  • 3-hydroxy-3-methylglutarate-CoA lyase
  • 3-hydroxy-3-methylglutaryl-Coenzyme A lyase
  • 3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyase
  • HL
  • HMGCL_HUMAN
  • HMG-CoA lyase

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 HMGCL?

acidosis ; acids ; amino acid ; arginine ; breakdown ; CoA ; coenzyme A ; deficiency ; enzyme ; fasting ; gene ; glucose ; glutamine ; hypoglycemia ; leucine ; mitochondria ; mutation ; population ; protein ; simple sugar

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

References

  • Al-Sayed M, Imtiaz F, Alsmadi OA, Rashed MS, Meyer BF. Mutations underlying 3-hydroxy-3-methylglutaryl CoA lyase deficiency in the Saudi population. BMC Med Genet. 2006 Dec 16;7:86. (http://www.ncbi.nlm.nih.gov/pubmed/17173698?dopt=Abstract)
  • Ashmarina LI, Pshezhetsky AV, Branda SS, Isaya G, Mitchell GA. 3-Hydroxy-3-methylglutaryl coenzyme A lyase: targeting and processing in peroxisomes and mitochondria. J Lipid Res. 1999 Jan;40(1):70-5. (http://www.ncbi.nlm.nih.gov/pubmed/9869651?dopt=Abstract)
  • Cardoso ML, Rodrigues MR, Leão E, Martins E, Diogo L, Rodrigues E, Garcia P, Rolland MO, Vilarinho L. The E37X is a common HMGCL mutation in Portuguese patients with 3-hydroxy-3-methylglutaric CoA lyase deficiency. Mol Genet Metab. 2004 Aug;82(4):334-8. (http://www.ncbi.nlm.nih.gov/pubmed/15308132?dopt=Abstract)
  • Casals N, Gómez-Puertas P, Pié J, Mir C, Roca R, Puisac B, Aledo R, Clotet J, Menao S, Serra D, Asins G, Till J, Elias-Jones AC, Cresto JC, Chamoles NA, Abdenur JE, Mayatepek E, Besley G, Valencia A, Hegardt FG. Structural (betaalpha)8 TIM barrel model of 3-hydroxy-3-methylglutaryl-coenzyme A lyase. J Biol Chem. 2003 Aug 1;278(31):29016-23. Epub 2003 May 13. (http://www.ncbi.nlm.nih.gov/pubmed/12746442?dopt=Abstract)
  • Fu Z, Runquist JA, Forouhar F, Hussain M, Hunt JF, Miziorko HM, Kim JJ. Crystal structure of human 3-hydroxy-3-methylglutaryl-CoA Lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria. J Biol Chem. 2006 Mar 17;281(11):7526-32. Epub 2005 Dec 5. (http://www.ncbi.nlm.nih.gov/pubmed/16330550?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3155)
  • Pie J, Casals N, Puisac B, Hegardt FG. Molecular basis of 3-hydroxy-3-methylglutaric aciduria. J Physiol Biochem. 2003 Dec;59(4):311-21. (http://www.ncbi.nlm.nih.gov/pubmed/15164951?dopt=Abstract)
  • Pié J, López-Viñas E, Puisac B, Menao S, Pié A, Casale C, Ramos FJ, Hegardt FG, Gómez-Puertas P, Casals N. Molecular genetics of HMG-CoA lyase deficiency. Mol Genet Metab. 2007 Nov;92(3):198-209. Epub 2007 Aug 9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17692550?dopt=Abstract)
  • Puisac B, López-Viñas E, Moreno S, Mir C, Pérez-Cerdá C, Menao S, Lluch D, Pié A, Gómez-Puertas P, Casals N, Ugarte M, Hegardt F, Pié J. Skipping of exon 2 and exons 2 plus 3 of HMG-CoA lyase (HL) gene produces the loss of beta sheets 1 and 2 in the recently proposed (beta-alpha)8 TIM barrel model of HL. Biophys Chem. 2005 Apr 1;115(2-3):241-5. Epub 2005 Jan 6. (http://www.ncbi.nlm.nih.gov/pubmed/15752612?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: October 2008
Published: February 23, 2015