HMGCL

Chr 1

3-hydroxy-3-methylglutaryl-CoA lyase

Also known as: HL, HMGCL1

NCBI Gene: 3155 ENSG00000117305 UniProt: P35914

The encoded mitochondrial enzyme catalyzes the final step of leucine degradation and is essential for ketone body formation. Mutations cause HMG-CoA lyase deficiency, an autosomal recessive disorder characterized by episodes of metabolic acidosis, hypoglycemia, and hyperammonemia, typically triggered by fasting or illness. The pathogenic mechanism involves loss of enzyme function leading to impaired ketogenesis and toxic accumulation of leucine metabolites.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene belongs to the HMG-CoA lyase family. It is a mitochondrial enzyme that catalyzes the final step of leucine degradation and plays a key role in ketone body formation. Mutations in this gene are associated with HMG-CoA lyase deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProt3-hydroxy-3-methylglutaryl-CoA lyase deficiency

Clinical highlights

Gene-disease validity (ClinGen)

3-hydroxy-3-methylglutaric aciduria · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.11

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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