HLCS Gene - Holocarboxylase Synthetase
Genetic and Functional Insights into Biotin Metabolism
Gene Information Card
| Symbol | HLCS |
|---|---|
| Full Name | Holocarboxylase Synthetase (biotin-[propionyl-CoA-carboxylase (ATP-hydrolysing)] ligase) |
| Gene Type | Protein coding |
| Chromosomal Location | 21q22.13 |
| NCBI Gene ID | 3141 ncbi.nlm.nih.gov/gene/3141 |
| Ensembl ID | ENSG00000159267 |
| UniProt ID | P50747 |
| OMIM ID | 609018 |
| HGNC ID | 4976 |
| Aliases | HCS, biotin-protein ligase |
Description
The HLCS gene encodes holocarboxylase synthetase, a biotin-protein ligase that catalyzes the covalent attachment of biotin to specific lysine residues in carboxylase enzymes. This biotinylation is essential for the activity of multiple carboxylases involved in gluconeogenesis, fatty acid synthesis, and amino acid catabolism. Mutations in HLCS cause holocarboxylase synthetase deficiency (multiple carboxylase deficiency), an autosomal recessive disorder of biotin metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Holocarboxylase synthetase deficiency | Loss-of-function mutations impair biotinylation of carboxylases, leading to metabolic acidosis and organic aciduria | ClinVar, OMIM |
| Multiple carboxylase deficiency | Deficient biotin attachment to propionyl-CoA carboxylase, pyruvate carboxylase, and 3-methylcrotonyl-CoA carboxylase | OMIM, NCBI Gene |
| Biotin-responsive multiple carboxylase deficiency | Some HLCS mutations respond to high-dose biotin supplementation | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Brain | 5.1 | Low |
| Heart | 6.7 | Low |
| Skeletal muscle | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| HEK293 | 10.8 | Embryonic kidney cells |
| K562 | 7.4 | Leukemia cell line |
| A549 | 6.1 | Lung carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1522C>T (p.Arg508Trp) | Missense | Common in European populations | Loss of biotin-binding affinity |
| c.1648G>A (p.Val550Met) | Missense | Rare | Reduced enzymatic activity |
| c.1990C>T (p.Arg664Cys) | Missense | Reported in multiple families | Impaired biotinylation |
| c.2341delG (p.Ala781Profs*13) | Frameshift | Rare | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most HLCS mutations are loss-of-function, reducing or abolishing biotin ligase activity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects described; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • biotin-[propionyl-CoA-carboxylase (ATP-hydrolysing)] ligase activity (GO:0004077) | • ATP binding (GO:0005524) |
| • cytoplasm (GO:0005737) | • isoleucine metabolic process (GO:0006549) |
| • fatty acid biosynthetic process (GO:0006633) |
Pathways
• Biotin metabolism (Reactome: R-HSA-196780)
• Metabolism of vitamins and cofactors (Reactome: R-HSA-196849)
Protein Summary
Holocarboxylase synthetase (HCS) is a 726-amino acid protein that uses ATP to catalyze the biotinylation of apocarboxylases. It contains a biotin-binding domain and a catalytic domain. The enzyme is critical for activating biotin-dependent carboxylases in multiple metabolic pathways. Deficiency leads to metabolic acidosis, ketosis, and neurological symptoms, often treatable with biotin supplementation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HLCS Knockout HEK293 Cell Line | EDJ-KQ13759 | Human | 3141 | Details Get a Quote |
| HLCS Knockout HeLa Cell Line | EDJ-KQ18052 | Human | 3141 | Details Get a Quote |
| HLCS Knockout A-549 Cell Line | EDJ-KQ43541 | Human | 3141 | Details Get a Quote |
| HLCS Knockout HCT 116 Cell Line | EDJ-KQ43542 | Human | 3141 | Details Get a Quote |
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