HACL1 (2-Hydroxyacyl-CoA Lyase 1)
Peroxisomal enzyme involved in phytanic acid metabolism and Refsum disease
Gene Information Card
| Symbol | HACL1 |
|---|---|
| Full Name | 2-Hydroxyacyl-CoA Lyase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 3p26.2 |
| NCBI Gene ID | 26061 ncbi.nlm.nih.gov/gene/26061 |
| Ensembl ID | ENSG00000164050 |
| UniProt ID | Q9UJ83 |
| OMIM ID | 617830 |
| HGNC ID | 24998 |
| Aliases | HPCL, HACL1, 2-hydroxyphytanoyl-CoA lyase |
Description
HACL1 encodes 2-hydroxyacyl-CoA lyase 1, a peroxisomal enzyme that catalyzes the cleavage of 2-hydroxyacyl-CoA substrates, a key step in the alpha-oxidation of branched-chain fatty acids such as phytanic acid. This enzyme is essential for the degradation of phytanic acid, which accumulates in Refsum disease. HACL1 is expressed in liver, kidney, and other tissues with high peroxisomal activity. Mutations in HACL1 cause a form of Refsum disease (RD) and are associated with peroxisomal biogenesis disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Refsum disease (RD) | Loss-of-function mutations in HACL1 impair alpha-oxidation of phytanic acid, leading to its accumulation in tissues. | ClinVar, OMIM |
| Peroxisomal biogenesis disorder type 1B (PBD1B) | Deficiency of HACL1 disrupts peroxisomal alpha-oxidation, contributing to the phenotype. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | High |
| Kidney | 8.7 | Medium |
| Small intestine | 6.1 | Medium |
| Heart | 4.2 | Low |
| Brain | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.5 | Hepatocellular carcinoma cell line |
| HEK293 | 9.2 | Embryonic kidney cells |
| HeLa | 5.0 | Cervical cancer cells |
| SH-SY5Y | 3.1 | Neuroblastoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.682C>T (p.Arg228*) | Nonsense | Rare | Loss of function; associated with Refsum disease |
| c.1000G>A (p.Gly334Arg) | Missense | Rare | Impaired enzyme activity; reported in Refsum disease |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; pathogenic |
Mutation functional classification
Loss of Function (LOF)
Nonsense and start-loss mutations lead to truncated or absent protein, reducing alpha-oxidation activity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • 2-hydroxyacyl-CoA lyase activity (GO:0003988) | • peroxisome (GO:0005777) |
| • fatty acid alpha-oxidation (GO:0006631) | • oxidation-reduction process (GO:0055114) |
Pathways
• REACTOME: Alpha-oxidation of phytanic acid (R-HSA-389661)
• KEGG: Peroxisome (hsa04146)
Protein Summary
2-hydroxyacyl-CoA lyase 1 is a 60 kDa peroxisomal protein that cleaves 2-hydroxyacyl-CoA substrates into formyl-CoA and a shortened fatty aldehyde. It is a key enzyme in the alpha-oxidation pathway, necessary for the breakdown of branched-chain fatty acids like phytanic acid. The protein is localized in the peroxisomal matrix and requires thiamine pyrophosphate as a cofactor. Defects in HACL1 lead to accumulation of phytanic acid, causing Refsum disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HACL1 Knockout HEK293 Cell Line | EDJ-KQ7705 | Human | 26061 | Details Get a Quote |
| HACL1 Knockout A-549 Cell Line | EDJ-KQ34428 | Human | 26061 | Details Get a Quote |
| HACL1 Knockout HCT 116 Cell Line | EDJ-KQ34429 | Human | 26061 | Details Get a Quote |
| HACL1 Knockout HeLa Cell Line | EDJ-KQ34430 | Human | 26061 | Details Get a Quote |
