HMGCL encodes 3-hydroxy-3-methylglutaryl-CoA lyase (325 aa). Mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis. Highest expression in Liver (77.6 TPM) and Adrenal Gland (34.4 TPM).

3-hydroxy-3-methylglutaric aciduria is caused by mutations in the HMGCL gene on chromosome 1.

The HMGCL protein participates in HMG CoA = acetoacetic acid + acetyl CoA pathway.

HMGCL is classified as a druggable target (Enzyme category) with score 0.0.

Genetic testing for HMGCL is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for 3-hydroxy-3-methylglutaric aciduria has been reported in the published literature.

Phenotype severity distribution: 2 always present features, 4 very common features, 19 common features.

Estimated prevalence: Unknown (Unknown prevalence).

1 clinical trial registered. Interventions under study include other interventions. Research is primarily sponsored by academic and government institutions.

14 publications have been identified in PubMed for 3-hydroxy-3-methylglutaric aciduria. Research spans Case Report / Case Series (57%), Review / Meta-Analysis (21%), and Diagnostic / Biomarker (7%).

Recent Publications

• Yang C (2026). [PMID: 41625680](https://pubmed.ncbi.nlm.nih.gov/41625680/). *O G Open*. [Case Report / Case Series]

• Newman S (2026). [PMID: 41529426](https://pubmed.ncbi.nlm.nih.gov/41529426/). *Mol Genet Metab*. [Review / Meta-Analysis]

• Yang K (2026). [PMID: 41872807](https://pubmed.ncbi.nlm.nih.gov/41872807/). *BMC Pediatr*. [Case Report / Case Series]

• Bjelica M (2025). [PMID: 40513556](https://pubmed.ncbi.nlm.nih.gov/40513556/). *J Pediatr Endocrinol Metab*. [Case Report / Case Series]

• Jennings EA (2025). [PMID: 40252717](https://pubmed.ncbi.nlm.nih.gov/40252717/). *Clin Chim Acta*. [Review / Meta-Analysis]

• Nyktari V (2025). [PMID: 41156202](https://pubmed.ncbi.nlm.nih.gov/41156202/). *J Clin Med*. [Case Report / Case Series]

• Menkovic I (2025). [PMID: 41323099](https://pubmed.ncbi.nlm.nih.gov/41323099/). *Mol Genet Metab Rep*. [Case Report / Case Series]

• Kılıç M (2025). [PMID: 41636194](https://pubmed.ncbi.nlm.nih.gov/41636194/). *Turk J Pediatr*. [Case Report / Case Series]

• Aukes R (2025). [PMID: 40937535](https://pubmed.ncbi.nlm.nih.gov/40937535/). *J Inherit Metab Dis*. [Review / Meta-Analysis]

• Demetriadou A (2025). [PMID: 40255048](https://pubmed.ncbi.nlm.nih.gov/40255048/). *J Inherit Metab Dis*. [Case Report / Case Series]