HLCS encodes holocarboxylase synthetase (726 aa). Biotin--protein ligase catalyzing the biotinylation of the 4 biotin-dependent carboxylases acetyl-CoA-carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase Highest expression in Pituitary (14.6 TPM) and Cells Cultured fibroblasts (12.2 TPM).

Holocarboxylase synthetase deficiency is caused by mutations in the HLCS gene on chromosome 21.

The HLCS protein participates in HLCS biotinylates PC:Mn2+, HLCS biotinylates ACACA:Mn2+, and HLCS biotinylates ACACB pathways.

HLCS is classified as a druggable target (Druggable Genome and Enzyme categories) with score 26.1.

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

Biomarker and diagnostic research for holocarboxylase synthetase deficiency has been reported in the published literature.

Phenotype severity distribution: 7 always present 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.

17 publications have been identified in PubMed for holocarboxylase synthetase deficiency. Research spans Case Report / Case Series (59%), Review / Meta-Analysis (24%), and Basic Science / Preclinical (12%).

Recent Publications

• Manoy S (2026). [PMID: 41383394](https://pubmed.ncbi.nlm.nih.gov/41383394/). *JIMD Rep*. [Case Report / Case Series]

• Woodliff B (2026). [PMID: 32809442](https://pubmed.ncbi.nlm.nih.gov/32809442/). *Unknown Journal*. [Review / Meta-Analysis]

• Treitel R (2025). [PMID: 40344499](https://pubmed.ncbi.nlm.nih.gov/40344499/). *Am J Med Genet A*. [Case Report / Case Series]

• Ting SL (2025). [PMID: 40051682](https://pubmed.ncbi.nlm.nih.gov/40051682/). *JIMD Rep*. [Basic Science / Preclinical]

• Nabbout R (2025). [PMID: 40192341](https://pubmed.ncbi.nlm.nih.gov/40192341/). *Epilepsia*. [Diagnostic / Biomarker]

• Zheng Z (2025). [PMID: 41029453](https://pubmed.ncbi.nlm.nih.gov/41029453/). *Orphanet J Rare Dis*. [Case Report / Case Series]

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

• Ren Y (2025). [PMID: 40231198](https://pubmed.ncbi.nlm.nih.gov/40231198/). *Metabol Open*. [Case Report / Case Series]

• Alagappan A (2025). [PMID: 40959364](https://pubmed.ncbi.nlm.nih.gov/40959364/). *Cureus*. [Case Report / Case Series]

• Azizinejad F (2025). [PMID: 39461572](https://pubmed.ncbi.nlm.nih.gov/39461572/). *Gene*. [Basic Science / Preclinical]