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HMGCL gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

HMGCL gene

The HMGCL gene provides instructions for creating an enzyme critical for processing leucine and producing ketones for energy.

Normal Function

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.

Health Conditions Related to Genetic Changes

3-hydroxy-3-methylglutaryl-CoA lyase deficiency

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. 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 glucose 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.

Other Names for This Gene

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

Genomic Location

The HMGCL gene is found on chromosome 1.

Frequently Asked Questions

Infants with HMG-CoA lyase deficiency often show symptoms during periods of fasting or illness, which trigger the body to use fats for energy. Early signs can include poor feeding, vomiting, lethargy, irritability, and seizures. If untreated, these can progress to coma and life-threatening complications due to severe hypoglycemia (low blood sugar) and metabolic acidosis (acid buildup in the blood).
Yes, HMG-CoA lyase deficiency is an inherited condition. It is passed down in an autosomal recessive pattern. This means a child must inherit two copies of the mutated HMGCL gene, one from each parent, to develop the condition. Parents who each carry one copy of the mutated gene are typically unaffected but have a 25% chance with each pregnancy of having a child with the deficiency.
Management primarily involves a strict diet to prevent metabolic crises. This typically includes frequent, small meals to avoid fasting, a low-leucine diet (limiting protein intake), and sometimes a special fat called medium-chain triglycerides (MCTs) to provide an alternative energy source. Regular monitoring by a metabolic specialist and prompt treatment during illness are crucial.
Diagnosis often begins with newborn screening in many regions, which can detect abnormal levels of certain metabolites. If screening is positive or symptoms appear, further tests include blood and urine organic acid analysis, acylcarnitine profile, and plasma amino acid analysis. Genetic testing to identify mutations in the HMGCL gene confirms the diagnosis.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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