ACLY (ATP Citrate Lyase): Structure, Function, and Disease Relevance
A comprehensive overview of the ACLY gene, including its genomic context, protein function, expression patterns, associated diseases, and clinical significance.
Gene Information Card
| Symbol | ACLY |
|---|---|
| Full Name | ATP citrate lyase |
| Gene Type | protein coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 47 ncbi.nlm.nih.gov/gene/47 |
| Ensembl ID | ENSG00000131473 |
| UniProt ID | P53396 |
| OMIM ID | 108731 |
| HGNC ID | 115 |
| Aliases | ACL, ATPCL, CLATP |
Description
The ACLY gene encodes ATP citrate lyase, a cytosolic enzyme that catalyzes the cleavage of citrate to oxaloacetate and acetyl-CoA, with the concomitant hydrolysis of ATP to ADP and phosphate. This reaction is a critical link between carbohydrate metabolism and lipid synthesis, providing the acetyl-CoA necessary for de novo fatty acid and cholesterol biosynthesis. ACLY is a key regulatory node in cellular metabolism and is often upregulated in cancers and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Cancer Predisposition | Germline mutations in ACLY are rare, but somatic alterations can contribute to tumorigenesis by promoting lipogenesis and supporting uncontrolled cell proliferation. | COSMIC, PubMed |
| Metabolic Syndrome | Altered ACLY expression and activity are associated with dyslipidemia, insulin resistance, and hepatic steatosis, contributing to the pathophysiology of metabolic syndrome. | OMIM, PubMed |
| Cancer (various types) | ACLY is overexpressed in multiple cancers (e.g., breast, prostate, lung, liver). It supports cancer cell growth by providing acetyl-CoA for lipid membrane synthesis and epigenetic modifications. | COSMIC, PubMed |
| Type 2 Diabetes | Increased ACLY activity in the liver promotes lipid accumulation, contributing to insulin resistance and hyperglycemia. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | High |
| Adipose Tissue | High | High |
| Brain | Medium | Medium |
| Kidney | Medium | Medium |
| Skeletal Muscle | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (Liver) | High | High expression consistent with lipogenic role |
| MCF7 (Breast) | High | Overexpressed in breast cancer cell lines |
| A549 (Lung) | Medium | Moderate expression in lung cancer cells |
| PC3 (Prostate) | High | High expression in prostate cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1715C>T (p.Pro572Leu) | Missense | Rare | Potential impact on enzyme activity; clinical significance not fully established. |
| c.1930G>A (p.Val644Ile) | Missense | Rare | Potential impact on enzyme activity; clinical significance not fully established. |
| c.2242A>G (p.Thr748Ala) | Missense | Rare | Potential impact on enzyme activity; clinical significance not fully established. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ACLY are rare and often embryonic lethal in model organisms. In humans, complete loss is not well-documented, but partial loss may impair lipogenesis and energy homeostasis.
Gain of Function (GOF)
Gain-of-function alterations, primarily through gene amplification or increased transcription, are common in cancers, leading to enhanced lipogenesis and tumor growth.
Dominant Negative (DN)
Dominant-negative effects are not well-characterized for ACLY. Most pathogenic alterations are likely haploinsufficient or result in altered enzyme kinetics.
View complete mutation data：
Gene Ontology (GO)
| • ATP citrate synthase activity | • citrate (Si)-synthase activity |
| • ATP binding | • metal ion binding |
| • acetyl-CoA biosynthetic process | • fatty acid biosynthetic process |
| • cholesterol biosynthetic process | • lipid homeostasis |
Pathways
• De novo lipogenesis
• Cholesterol biosynthesis
• Glycolysis
• Citrate cycle (TCA cycle)
• Insulin signaling
• AMPK signaling
Protein Summary
ATP citrate lyase (ACLY) is a homotetrameric cytosolic enzyme. It catalyzes the ATP-dependent conversion of citrate and CoA into acetyl-CoA and oxaloacetate. This reaction is a primary source of cytosolic acetyl-CoA, a building block for fatty acids and cholesterol. ACLY activity is regulated by allosteric effectors (e.g., citrate, ATP) and post-translational modifications, including phosphorylation by kinases such as AKT and AMPK. Its expression is highly responsive to nutritional and hormonal signals, and it is a central node in cellular metabolism, linking glucose metabolism to lipid synthesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACLY Knockout A-549 Cell Line | EDC90704 | Human | 47 | Details Get a Quote |
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