ACOT8: Acyl-CoA Thioesterase 8
Key regulator of fatty acid metabolism and peroxisomal β-oxidation
Gene Information Card
| Symbol | ACOT8 |
|---|---|
| Full Name | Acyl-CoA Thioesterase 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.12 |
| NCBI Gene ID | 10005 ncbi.nlm.nih.gov/gene/10005 |
| Ensembl ID | ENSG00000101473 |
| UniProt ID | O14734 |
| OMIM ID | 608123 |
| HGNC ID | 15919 |
| Aliases | PTE1, PTE-1, hACTE-III, hPTE |
Description
ACOT8 encodes a peroxisomal acyl-CoA thioesterase that catalyzes the hydrolysis of acyl-CoAs to free fatty acids and coenzyme A. It plays a critical role in lipid metabolism, particularly in peroxisomal β-oxidation, and regulates intracellular levels of acyl-CoA esters. The enzyme exhibits broad substrate specificity, acting on medium- and long-chain acyl-CoAs, and is involved in bile acid synthesis and detoxification of branched-chain fatty acids.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Peroxisomal biogenesis disorders (Zellweger spectrum) | Dysfunctional peroxisomal β-oxidation due to ACOT8 deficiency may contribute to accumulation of very long-chain fatty acids | Inferred from functional studies and peroxisomal disease models (OMIM #608123) |
| Hepatocellular carcinoma | Altered ACOT8 expression linked to disrupted lipid metabolism in liver cancer | COSMIC database reports somatic mutations in ACOT8 in liver tumors |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Small intestine | 7.1 | Medium |
| Heart | 4.2 | Low |
| Brain | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.0 | Hepatocellular carcinoma cell line |
| HEK293 | 6.5 | Embryonic kidney cells |
| HeLa | 3.2 | Cervical cancer cells |
| A549 | 2.1 | Lung carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon; predicted loss of function |
| c.374C>T (p.Thr125Met) | Missense | <0.01% | Unknown effect; rare variant in population databases |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Met1?) are predicted to abolish protein function, potentially impairing peroxisomal lipid metabolism.
Gain of Function (GOF)
No gain-of-function mutations reported in ACOT8.
Dominant Negative (DN)
No dominant-negative mutations described for ACOT8.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003986 - acetyl-CoA hydrolase activity | • GO:0016290 - palmitoyl-CoA hydrolase activity |
| • GO:0005777 - peroxisome | • GO:0006631 - fatty acid metabolic process |
| • GO:0042760 - very long-chain fatty acid catabolic process |
Pathways
• Peroxisomal β-oxidation (Reactome: R-HSA-390247)
• Fatty acid metabolism (KEGG: hsa00071)
• Bile acid biosynthesis (Reactome: R-HSA-192105)
Protein Summary
ACOT8 is a 40 kDa peroxisomal enzyme belonging to the acyl-CoA thioesterase family. It contains a type 1 peroxisomal targeting signal (PTS1) at its C-terminus (SKL) and functions as a homodimer. The protein hydrolyzes a wide range of acyl-CoA substrates, including palmitoyl-CoA and branched-chain acyl-CoAs, thereby modulating lipid signaling and energy homeostasis. Its crystal structure reveals a hotdog-fold domain characteristic of thioesterases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACOT8 Knockout HEK293 Cell Line | EDJ-KQ6860 | Human | 10005 | Details Get a Quote |
| ACOT8 Knockout A-549 Cell Line | EDJ-KQ31434 | Human | 10005 | Details Get a Quote |
| ACOT8 Knockout HCT 116 Cell Line | EDJ-KQ31435 | Human | 10005 | Details Get a Quote |
| ACOT8 Knockout HeLa Cell Line | EDC08237 | Human | 10005 | Details Get a Quote |
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