ACSS3: Acyl-CoA Synthetase Short Chain Family Member 3
Mitochondrial acetyl-CoA synthetase involved in acetate metabolism and energy homeostasis
Gene Information Card
| Symbol | ACSS3 |
|---|---|
| Full Name | Acyl-CoA Synthetase Short Chain Family Member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q21.31 |
| NCBI Gene ID | 79611 ncbi.nlm.nih.gov/gene/79611 |
| Ensembl ID | ENSG00000111011 |
| UniProt ID | Q9H6R3 |
| OMIM ID | 614355 |
| HGNC ID | 24722 |
| Aliases | ACS3, ACSS3, acyl-CoA synthetase short-chain family member 3 |
Description
ACSS3 encodes a mitochondrial acyl-CoA synthetase that catalyzes the conversion of acetate to acetyl-CoA, a key step in acetate utilization and energy production. The enzyme is primarily expressed in tissues with high metabolic demand, such as liver, kidney, and heart, and plays a role in lipid biosynthesis and ketone body metabolism. Alternative splicing results in multiple transcript variants.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Altered acetate metabolism; ACSS3 overexpression may promote tumor growth by providing acetyl-CoA for lipid synthesis | PMID: 30872518 |
| Colorectal cancer | Upregulation of ACSS3 linked to poor prognosis; contributes to Warburg effect via acetate-dependent acetyl-CoA production | PMID: 31570769 |
| Metabolic syndrome | Variants in ACSS3 associated with altered lipid profiles and insulin resistance in genome-wide association studies | PMID: 25664888 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Heart | 6.1 | Medium |
| Skeletal Muscle | 4.2 | Low |
| Brain | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.2 | Hepatocellular carcinoma cell line |
| HEK293 | 5.6 | Embryonic kidney cells |
| MCF7 | 3.1 | Breast cancer cell line |
| A549 | 2.4 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | 0.0002 | Reduced enzyme activity; associated with altered acetate metabolism |
| c.1246G>A (p.Gly416Ser) | Missense | 0.0001 | Decreased stability; potential loss-of-function |
| c.1789_1791del (p.Phe597del) | In-frame deletion | <0.0001 | Unknown functional impact |
Mutation functional classification
Loss of Function (LOF)
Missense variants such as p.Arg339Trp and p.Gly416Ser reduce catalytic activity or protein stability, impairing acetate conversion to acetyl-CoA.
Gain of Function (GOF)
No documented gain-of-function mutations in ACSS3.
Dominant Negative (DN)
No evidence for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003987 - acetate-CoA ligase activity | • GO:0005739 - mitochondrion |
| • GO:0006085 - acetyl-CoA biosynthetic process | • GO:0006631 - fatty acid metabolic process |
| • GO:0016874 - ligase activity |
Pathways
• Acetate metabolism (Reactome: R-HSA-77108)
• Metabolism of lipids (Reactome: R-HSA-556833)
• Propanoate metabolism (KEGG: hsa00640)
Protein Summary
ACSS3 is a 689-amino acid mitochondrial protein that belongs to the acyl-CoA synthetase family. It catalyzes the ATP-dependent ligation of acetate to coenzyme A, forming acetyl-CoA. This reaction is critical for acetate utilization in energy metabolism, lipid synthesis, and histone acetylation. The enzyme is highly expressed in liver and kidney, and its dysregulation is implicated in cancer and metabolic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACSS3 Knockout HEK293 Cell Line | EDC09645 | Human | 79611 | Details Get a Quote |
| ACSS3 Knockout A-549 Cell Line | EDJ-KQ18117 | Human | 79611 | Details Get a Quote |
| ACSS3 Knockout HeLa Cell Line | EDJ-KQ57192 | Human | 79611 | Details Get a Quote |
| ACSS3 Knockout HCT 116 Cell Line | EDJ-KQ74124 | Human | 79611 | Details Get a Quote |
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