ACSL5 (Acyl-CoA Synthetase Long Chain Family Member 5): A Key Regulator of Lipid Metabolism and Cancer Biology
Comprehensive gene resource for ACSL5, covering genomic annotation, tissue expression, disease associations, mutations, and functional pathways.
Gene Information Card
| Symbol | ACSL5 |
|---|---|
| Full Name | Acyl-CoA Synthetase Long Chain Family Member 5 |
| Gene Type | protein coding |
| Chromosomal Location | 10q25.2 |
| NCBI Gene ID | 51703 ncbi.nlm.nih.gov/gene/51703 |
| Ensembl ID | ENSG00000197142 |
| UniProt ID | Q9ULC5 |
| OMIM ID | 605677 |
| HGNC ID | 16037 |
| Aliases | ACS2, ACS5, FACL5, FLJ42957 |
Description
ACSL5 (Acyl-CoA Synthetase Long Chain Family Member 5) encodes a member of the long-chain acyl-CoA synthetase family. This enzyme catalyzes the ATP-dependent activation of long-chain fatty acids (C16-C20) to their CoA derivatives, a critical first step in fatty acid metabolism. This activation is essential for both fatty acid degradation via beta-oxidation and for the synthesis of complex lipids like triglycerides and phospholipids. ACSL5 is localized to the mitochondria and is implicated in the regulation of apoptosis and cell proliferation. Its expression is particularly notable in the small intestine, liver, and certain cancer types, where it plays a complex and context-dependent role in tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Colorectal Cancer | ACSL5 expression is frequently downregulated in colorectal cancer. Loss of ACSL5 promotes resistance to apoptosis (e.g., butyrate-induced apoptosis) and enhances cell proliferation, contributing to tumor progression. | PMID: 15623653, PMID: 21159672 |
| Glioblastoma | ACSL5 expression is elevated in glioblastoma and is associated with poor patient prognosis. It promotes tumor cell proliferation and survival by modulating lipid metabolism and the PI3K/Akt signaling pathway. | PMID: 30827901 |
| Hepatocellular Carcinoma | ACSL5 expression is upregulated in hepatocellular carcinoma (HCC) and is associated with aggressive tumor features. It may contribute to cancer cell growth by enhancing fatty acid utilization and lipid droplet formation. | PMID: 29295995 |
| Prostate Cancer | ACSL5 expression is increased in prostate cancer and is linked to disease progression. It may support cancer cell survival by regulating lipid metabolism and androgen receptor signaling. | PMID: 29295995 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Small Intestine | 120.7 | High |
| Liver | 58.3 | Medium |
| Adipose Tissue | 48.2 | Medium |
| Colon | 45.1 | Medium |
| Kidney | 25.4 | Low |
| Lung | 10.2 | Low |
| Brain | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HepG2 (Liver) | 85.3 | High expression, consistent with liver function. |
| Caco-2 (Colon) | 72.1 | High expression, relevant to intestinal metabolism. |
| MCF7 (Breast) | 15.4 | Moderate expression. |
| A549 (Lung) | 8.2 | Low expression. |
| U87MG (Glioblastoma) | 45.6 | Elevated expression, consistent with cancer studies. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.1058C>T (p.Pro353Leu) | Missense | Rare (MAF < 0.01) | Reported in ClinVar; functional impact not fully characterized, may affect protein stability. |
| c.1774G>A (p.Val592Ile) | Missense | Rare (MAF < 0.01) | Reported in ClinVar; likely benign, but further studies are needed. |
| c.2149A>G (p.Ile717Val) | Missense | Rare (MAF < 0.01) | Reported in ClinVar; uncertain significance. |
| c.1265C>T (p.Thr422Met) | Missense | Rare (MAF < 0.01) | Reported in ClinVar; uncertain significance. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ACSL5 are not well-documented in germline disease, but somatic downregulation or epigenetic silencing is common in colorectal cancer, leading to reduced apoptosis and increased proliferation.
Gain of Function (GOF)
Gain-of-function or overexpression of ACSL5 is observed in several cancers (e.g., glioblastoma, HCC), where it promotes cell survival and proliferation by enhancing lipid metabolism.
Dominant Negative (DN)
No dominant-negative mutations have been reported for ACSL5.
View complete mutation data：
Gene Ontology (GO)
| • long-chain fatty acid-CoA ligase activity | • ATP binding |
| • fatty acid binding | • very long-chain fatty acid-CoA ligase activity |
| • lipid metabolic process | • long-chain fatty acid metabolic process |
| • fatty acid beta-oxidation | • phospholipid biosynthetic process |
| • triglyceride biosynthetic process | • mitochondrion |
| • peroxisome | • endoplasmic reticulum membrane |
Pathways
• Fatty acid metabolism
• PPAR signaling pathway
• AMPK signaling pathway
• Metabolic reprogramming in cancer
• Biosynthesis of unsaturated fatty acids
Protein Summary
The ACSL5 protein is a 683-amino acid enzyme localized primarily to the mitochondrial outer membrane. It belongs to the acyl-CoA synthetase family and is crucial for the 'activation' of long-chain fatty acids. By converting fatty acids into fatty acyl-CoA esters, ACSL5 channels these substrates towards either energy production via beta-oxidation or towards lipid synthesis. Its activity is regulated by cellular energy status and is involved in integrating metabolic signals with cell fate decisions, particularly apoptosis. In cancer, ACSL5's role is context-dependent, acting as a tumor suppressor in some tissues (e.g., colon) and an oncogene in others (e.g., brain, liver).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACSL5 Knockout HEK293 Cell Line | EDJ-KQ11194 | Human | 51703 | Details Get a Quote |
| ACSL5 Knockout HCT 116 Cell Line | EDJ-KQ39248 | Human | 51703 | Details Get a Quote |
| ACSL5 Knockout HeLa Cell Line | EDJ-KQ39249 | Human | 51703 | Details Get a Quote |
| ACSL5 Knockout A-549 Cell Line | EDJ-KQ64838 | Human | 51703 | Details Get a Quote |
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