ACAT1 Gene (Acetyl-CoA Acetyltransferase 1)
Key enzyme in ketone body metabolism and cholesterol biosynthesis; mutations linked to beta-ketothiolase deficiency
Gene Information Card
| Symbol | ACAT1 |
|---|---|
| Full Name | Acetyl-CoA Acetyltransferase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q22.3 |
| NCBI Gene ID | 38 ncbi.nlm.nih.gov/gene/38 |
| Ensembl ID | ENSG00000175274 |
| UniProt ID | P24752 |
| OMIM ID | 607809 |
| HGNC ID | 93 |
| Aliases | MAT, T2, THIL, ACAT, ACAT1, beta-ketothiolase |
Description
The ACAT1 gene encodes the mitochondrial enzyme acetyl-CoA acetyltransferase 1 (also known as beta-ketothiolase), which catalyzes the reversible thiolytic cleavage of acetoacetyl-CoA to two molecules of acetyl-CoA. This enzyme is critical for ketone body metabolism (ketolysis) and the degradation of isoleucine. Mutations in ACAT1 cause beta-ketothiolase deficiency (OMIM 203750), an autosomal recessive disorder of ketone body and isoleucine metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Beta-ketothiolase deficiency (OMIM 203750) | Loss-of-function mutations impair acetoacetyl-CoA cleavage, leading to accumulation of toxic metabolites and episodic ketoacidosis | ClinVar, OMIM |
| 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (differential diagnosis) | Indirect; ACAT1 deficiency mimics HMGCL deficiency due to overlapping metabolic pathways | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Heart | 6.1 | Medium |
| Brain | 4.2 | Low |
| Skeletal muscle | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocyte line; high expression |
| HEK293 | 7.8 | Embryonic kidney; moderate expression |
| K562 | 4.5 | Myelogenous leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.622C>T (p.Arg208Trp) | Missense | 1.2% | Loss of enzyme activity; associated with beta-ketothiolase deficiency |
| c.1000G>A (p.Gly334Ser) | Missense | 0.8% | Reduced catalytic efficiency |
| c.149delC (p.Pro50Leufs*12) | Frameshift | 0.3% | Null allele; complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Most ACAT1 mutations are loss-of-function, reducing or abolishing thiolase activity, leading to beta-ketothiolase deficiency.
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)
| • acetyl-CoA C-acetyltransferase activity | • mitochondrion |
| • ketone body catabolic process | • isoleucine catabolic process |
| • fatty acid beta-oxidation |
Pathways
• Ketone body metabolism (Reactome R-HSA-77111)
• Isoleucine degradation (Reactome R-HSA-70895)
• Fatty acid metabolism (KEGG hsa00071)
Protein Summary
Acetyl-CoA acetyltransferase 1 (ACAT1) is a homotetrameric mitochondrial enzyme that catalyzes the reversible conversion of acetoacetyl-CoA to two acetyl-CoA molecules. It is essential for ketone body utilization in extrahepatic tissues and for the catabolism of isoleucine. The protein is encoded by the ACAT1 gene on chromosome 11q22.3. Deficiency leads to beta-ketothiolase deficiency, characterized by episodic ketoacidosis and urinary excretion of 2-methyl-3-hydroxybutyrate and tiglylglycine.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACAT1 Knockout HEK293 Cell Line | EDJ-KQ2122 | Human | 38 | Details Get a Quote |
| BLACAT1 Knockout HEK293 Cell Line | EDJ-KQ12119 | Human | 101669762 | Details Get a Quote |
| ACAT1 Knockout A-549 Cell Line | EDJ-KQ22270 | Human | 38 | Details Get a Quote |
| ACAT1 Knockout HCT 116 Cell Line | EDJ-KQ22271 | Human | 38 | Details Get a Quote |
| ACAT1 Knockout HeLa Cell Line | EDJ-KQ22272 | Human | 38 | Details Get a Quote |
| BLACAT1 Knockout HCT 116 Cell Line | EDJ-KQ39553 | Human | 101669762 | Details Get a Quote |
| BLACAT1 Knockout A-549 Cell Line | EDJ-KQ40806 | Human | 101669762 | Details Get a Quote |
| BLACAT1 Knockout HeLa Cell Line | EDJ-KQ40807 | Human | 101669762 | Details Get a Quote |
Displaying Records 1 To 8 Of 8 Records
