ATG14 (Autophagy Related 14) Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the ATG14 gene, its role in autophagy, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | ATG14 |
|---|---|
| Full Name | Autophagy Related 14 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.33 |
| NCBI Gene ID | 22863 ncbi.nlm.nih.gov/gene/22863 |
| Ensembl ID | ENSG00000100811 |
| UniProt ID | Q6ZNE5 |
| OMIM ID | 615104 |
| HGNC ID | 19908 |
| Aliases | ATG14L, KIAA0831, Barkor |
Description
ATG14 (Autophagy Related 14) encodes a key component of the class III phosphatidylinositol 3-kinase (PI3KC3) complex I, which is essential for autophagosome formation. The protein acts as a scaffold, recruiting the complex to the endoplasmic reticulum (ER) and regulating the nucleation of autophagosomal membranes. ATG14 is critical for autophagy initiation and plays roles in cellular homeostasis, immune response, and tumor suppression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Dysregulation of ATG14 expression alters autophagy flux, affecting tumor cell survival and metabolism. Loss of ATG14 can impair autophagy, promoting genomic instability and tumorigenesis. | COSMIC: somatic mutations and copy number alterations in multiple cancers; PubMed studies (e.g., PMID: 28388412) |
| Neurodegenerative disorders (e.g., Alzheimer's disease) | Impaired autophagy due to reduced ATG14 function leads to accumulation of misfolded proteins and neurotoxicity. | ClinVar: variants of uncertain significance; research articles (e.g., PMID: 30115702) |
| Infectious diseases (e.g., bacterial/viral infections) | ATG14-mediated autophagy is involved in xenophagy, the selective degradation of intracellular pathogens. Altered ATG14 expression can affect pathogen clearance. | PubMed studies (e.g., PMID: 27641601) |
| Metabolic disorders (e.g., type 2 diabetes) | Autophagy regulates insulin sensitivity and pancreatic beta-cell function. ATG14 variants may influence autophagy efficiency, contributing to metabolic dysregulation. | ClinVar: rare variants; research (e.g., PMID: 29127255) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | 10.2 | Medium |
| Heart | 8.5 | Medium |
| Liver | 7.8 | Medium |
| Brain | 6.4 | Low |
| Kidney | 5.9 | Low |
| Lung | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 12.5 | High expression; commonly used for autophagy studies |
| HEK293 (embryonic kidney) | 10.1 | Moderate expression; used for transfection assays |
| MCF7 (breast cancer) | 8.3 | Moderate expression; autophagy-related research |
| A549 (lung cancer) | 7.2 | Low expression; response to stress |
| HepG2 (liver cancer) | 6.8 | Low expression; metabolic studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare (0.01%) | Potential loss of start codon, leading to reduced protein expression; ClinVar: uncertain significance |
| c.125C>T (p.Thr42Met) | Missense | 0.05% | Located in the BATS domain; may affect membrane binding; ClinVar: uncertain significance |
| c.789_790del (p.Glu264fs) | Frameshift | Very rare | Predicted to cause truncation, likely loss of function; COSMIC: somatic in cancer |
| c.1000G>A (p.Glu334Lys) | Missense | 0.02% | In the coiled-coil domain; may disrupt protein-protein interactions; ClinVar: uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., frameshift, start codon loss) impair ATG14's ability to nucleate autophagosomes, leading to reduced autophagy. This can contribute to neurodegeneration and increased cancer risk.
Gain of Function (GOF)
Gain-of-function mutations are rare and not well characterized. Overexpression of ATG14 can enhance autophagy, potentially promoting cell survival under stress but also possibly facilitating tumor growth in certain contexts.
Dominant Negative (DN)
Dominant-negative mutations may interfere with the assembly of the PI3KC3-C1 complex, blocking autophagy even in the presence of wild-type ATG14. Such mutations are hypothesized but not yet confirmed in clinical databases.
View complete mutation data：
Gene Ontology (GO)
| • Autophagy | • Phosphatidylinositol 3-kinase complex assembly |
| • Protein homodimerization activity | • Lipid binding |
| • Membrane bending | • Response to starvation |
| • Cellular response to nitrogen starvation |
Pathways
• Autophagy - other
• PI3K-Akt signaling pathway (modulation)
• Mitophagy
• Xenophagy
• Selective autophagy
Protein Summary
ATG14 is a 492-amino acid protein with a molecular weight of ~55 kDa. It contains a BATS (Barkor/ATG14L autophagosome targeting) domain that mediates ER localization and a coiled-coil domain for interaction with Beclin 1 and VPS34. ATG14 is essential for autophagosome formation, acting as a subunit of the PI3KC3-C1 complex. It is ubiquitously expressed but enriched in tissues with high metabolic demand. Post-translational modifications include phosphorylation, which regulates its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATG14 Knockout HEK293 Cell Line | EDJ-KQ3841 | Human | 22863 | Details Get a Quote |
| ATG14 Knockout A-549 Cell Line | EDJ-KQ26001 | Human | 22863 | Details Get a Quote |
| ATG14 Knockout HCT 116 Cell Line | EDJ-KQ26002 | Human | 22863 | Details Get a Quote |
| ATG14 Knockout HeLa Cell Line | EDJ-KQ26003 | Human | 22863 | Details Get a Quote |
