ACSL4 Gene - Acyl-CoA Synthetase Long Chain Family Member 4
Key enzyme in fatty acid metabolism, lipid biosynthesis, and ferroptosis regulation
Gene Information Card
| Symbol | ACSL4 |
|---|---|
| Full Name | Acyl-CoA Synthetase Long Chain Family Member 4 |
| Gene Type | protein-coding |
| Chromosomal Location | Xq23 |
| NCBI Gene ID | 2182 ncbi.nlm.nih.gov/gene/2182 |
| Ensembl ID | ENSG00000068366 |
| UniProt ID | O60488 |
| OMIM ID | 300157 |
| HGNC ID | 3571 |
| Aliases | ACS4, FACL4, LACS4, MRX63, MRX68 |
Description
The ACSL4 gene encodes acyl-CoA synthetase long chain family member 4, an enzyme that catalyzes the conversion of long-chain fatty acids into their acyl-CoA derivatives. This activation is essential for fatty acid metabolism, lipid biosynthesis, and the regulation of cellular lipid composition. ACSL4 is particularly involved in the synthesis of polyunsaturated fatty acid-containing phospholipids, which are critical for membrane integrity and signaling. Notably, ACSL4 is a key mediator of ferroptosis, a form of regulated cell death driven by lipid peroxidation. Its expression is associated with various cancers and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | ACSL4 promotes ferroptosis and lipid remodeling, influencing tumor growth and response to therapy. | COSMIC; PubMed studies (e.g., PMID: 31209336) |
| Breast cancer | Overexpression of ACSL4 correlates with aggressive tumor phenotypes and poor prognosis, affecting lipid metabolism and cell proliferation. | COSMIC; PubMed studies (e.g., PMID: 28397838) |
| Colorectal cancer | ACSL4 expression modulates ferroptosis sensitivity and tumor progression, with potential as a therapeutic target. | COSMIC; PubMed studies (e.g., PMID: 31570770) |
| Alpers-Huttenlocher syndrome (AHS) | Mutations in ACSL4 are associated with AHS, a mitochondrial disorder characterized by seizures, developmental regression, and liver disease. | ClinVar; OMIM 300157 |
| X-linked intellectual disability | Loss-of-function mutations in ACSL4 cause non-syndromic intellectual disability, affecting neuronal lipid metabolism. | ClinVar; OMIM 300157 |
| Ferroptosis-related diseases | ACSL4 is a critical driver of ferroptosis, implicated in ischemia-reperfusion injury, neurodegeneration, and cancer therapy. | PubMed reviews (e.g., PMID: 31209336) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | 12.3 | Medium |
| Brain | 8.5 | Low |
| Liver | 6.2 | Low |
| Testis | 15.7 | Medium |
| Kidney | 4.1 | Low |
| Heart | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 18.5 | High expression; relevant to ferroptosis studies |
| MCF7 (breast cancer) | 22.3 | High expression; associated with aggressive phenotype |
| A549 (lung cancer) | 9.2 | Moderate expression |
| HeLa (cervical cancer) | 7.8 | Low expression |
| SH-SY5Y (neuroblastoma) | 5.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.157C>T (p.Arg53Ter) | Nonsense | Rare | Loss of function; associated with intellectual disability |
| c.1000G>A (p.Gly334Ser) | Missense | Rare | Loss of function; associated with Alpers-Huttenlocher syndrome |
| c.1234A>G (p.Thr412Ala) | Missense | Rare | Uncertain significance; possibly affects enzyme activity |
| c.1565T>C (p.Leu522Pro) | Missense | Rare | Loss of function; associated with intellectual disability |
| c.1780C>T (p.Arg594Trp) | Missense | Rare | Uncertain significance; possibly affects protein stability |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ACSL4, such as nonsense or missense variants that disrupt enzyme activity, lead to impaired fatty acid activation and lipid metabolism. These are associated with X-linked intellectual disability and Alpers-Huttenlocher syndrome.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented; however, overexpression of wild-type ACSL4 in cancers can enhance lipid synthesis and ferroptosis sensitivity, contributing to tumor progression.
Dominant Negative (DN)
No dominant-negative mutations have been reported for ACSL4. The gene is X-linked, and hemizygous loss in males or homozygous loss in females is typically required for phenotypic effects.
View complete mutation data：
Gene Ontology (GO)
| • long-chain fatty acid-CoA ligase activity | • ATP binding |
| • fatty acid metabolic process | • lipid biosynthetic process |
| • ferroptosis | • membrane |
| • endoplasmic reticulum | • peroxisome |
| • mitochondrion |
Pathways
• Fatty acid metabolism
• Triacylglycerol biosynthesis
• Phospholipid biosynthesis
• Ferroptosis signaling
• PPAR signaling pathway
Protein Summary
The ACSL4 protein is a 711-amino-acid enzyme localized to the endoplasmic reticulum, mitochondria, and peroxisomes. It catalyzes the ATP-dependent activation of long-chain fatty acids (C16-C22) to their acyl-CoA derivatives, with a preference for polyunsaturated fatty acids like arachidonic acid and eicosapentaenoic acid. This activity is crucial for lipid synthesis and membrane composition. ACSL4 is a key regulator of ferroptosis, as it promotes the incorporation of polyunsaturated fatty acids into phospholipids, making cells susceptible to lipid peroxidation. Its expression is tightly regulated and varies across tissues, with high levels in adrenal glands and testis. Dysregulation of ACSL4 is linked to cancer progression, neurological disorders, and metabolic diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACSL4 Knockout HEK293 Cell Line | EDJ-KQ12266 | Human | 2182 | Details Get a Quote |
| ACSL4 Knockout A-549 Cell Line | EDJ-KQ41065 | Human | 2182 | Details Get a Quote |
| ACSL4 Knockout HCT 116 Cell Line | EDJ-KQ41066 | Human | 2182 | Details Get a Quote |
| ACSL4 Knockout HeLa Cell Line | EDJ-KQ41067 | Human | 2182 | Details Get a Quote |
| ACSL4 Knockout L-02 Cell Line | EDJ-KZ526 | Human | 2182 | Details Get a Quote |
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