ATG12: Autophagy Related 12 Homolog
Key Ubiquitin-Like Conjugating System in Autophagy and Cellular Homeostasis
Gene Information Card
| Symbol | ATG12 |
|---|---|
| Full Name | autophagy related 12 |
| Gene Type | protein coding |
| Chromosomal Location | 5q22.3 |
| NCBI Gene ID | 9140 ncbi.nlm.nih.gov/gene/9140 |
| Ensembl ID | ENSG00000145782 |
| UniProt ID | O94817 |
| OMIM ID | 609389 |
| HGNC ID | 588 |
| Aliases | APG12, APG12L, HAPG12 |
Description
ATG12 (autophagy related 12) encodes a ubiquitin-like protein essential for autophagosome formation. ATG12 is conjugated to ATG5 via a ubiquitin-like conjugation system involving ATG7 and ATG10, forming the ATG12-ATG5 conjugate that functions as an E3-like ligase for LC3 lipidation. This process is critical for macroautophagy, a conserved pathway for degradation of cytoplasmic components. ATG12 also participates in non-autophagic processes including apoptosis and immune signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | Dysregulation of autophagy via ATG12 alterations may promote tumorigenesis | COSMIC; PMID: 25643397 |
| Colorectal Cancer | ATG12 overexpression linked to poor prognosis and autophagy activation | COSMIC; PMID: 27058445 |
| Neurodegenerative Disorders (e.g., Alzheimer's disease) | Impaired autophagy due to ATG12 dysfunction contributes to protein aggregation | ClinVar; PMID: 22153079 |
| Inflammatory Bowel Disease | ATG12 variants associated with altered autophagy and inflammation | ClinVar; PMID: 23128233 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | 12.5 | Medium |
| Heart | 10.2 | Medium |
| Liver | 8.7 | Medium |
| Brain | 6.3 | Low |
| Lung | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.8 | Cervical carcinoma cell line |
| HEK 293 | 11.2 | Embryonic kidney cells |
| MCF7 | 9.5 | Breast cancer cell line |
| HepG2 | 8.1 | Hepatocellular carcinoma |
| A549 | 7.3 | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.130G>A (p.Glu44Lys) | Missense | 0.001% (gnomAD) | Unknown functional impact |
| c.364C>T (p.Arg122Trp) | Missense | 0.002% (gnomAD) | Potential loss of function |
| c.485_486del (p.Glu162ValfsTer5) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations predicted to truncate ATG12, impairing autophagy.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Missense mutations in the ubiquitin-like domain may interfere with ATG5 binding, acting dominant-negative.
View complete mutation data：
Gene Ontology (GO)
| • GO:0006914 - autophagy | • GO:0015031 - protein transport |
| • GO:0019776 - Atg8 ligase activity | • GO:0034045 - pre-autophagosomal structure membrane |
| • GO:0043130 - ubiquitin-like protein conjugating enzyme activity | • GO:0005737 - cytoplasm |
Pathways
• Autophagy - animal (KEGG: hsa04140)
• Regulation of autophagy (Reactome: R-HSA-1632852)
• Ubiquitin-like conjugation (Reactome: R-HSA-8851238)
Protein Summary
ATG12 is a 140-amino acid ubiquitin-like protein (UniProt O94817) that lacks a C-terminal glycine for direct conjugation but is activated by ATG7 (E1-like) and transferred to ATG10 (E2-like) for conjugation to ATG5. The ATG12-ATG5 conjugate forms a complex with ATG16L1, acting as an E3-like ligase for LC3/GABARAP lipidation. ATG12 also contains a non-canonical mitochondrial targeting sequence and can regulate apoptosis via interaction with BCL2 family members. Post-translational modifications include ubiquitination and phosphorylation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATG12 Knockout HEK293 Cell Line | EDJ-KQ1541 | Human | 9140 | Details Get a Quote |
| ATG12 Knockout A-549 Cell Line | EDJ-KQ21206 | Human | 9140 | Details Get a Quote |
| ATG12 Knockout HeLa Cell Line | EDJ-KQ21208 | Human | 9140 | Details Get a Quote |
| ATG12 Knockout HCT 116 Cell Line | EDJ-KQ19844 | Human | 9140 | Details Get a Quote |
| ATG12 Knockout HAP1 Cell Line | EDC08004 | Human | 9140 | Details Get a Quote |
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