ATG5 Gene: Function, Mutations, and Disease Associations | Autophagy Research

ATG5 (Autophagy Related 5) encodes a protein that is essential for autophagosome formation, a key step in macroautophagy. The ATG5 protein forms a conjugate with ATG12, which then associates with ATG16L1 to form a complex that promotes the lipidation of LC3 (MAP1LC3A) at the autophagosome membrane. This process is critical for the degradation and recycling of cytoplasmic components, including damaged organelles and protein aggregates. ATG5 also plays roles in other cellular processes such as apoptosis, immune response, and tumor suppression. Mutations and dysregulation of ATG5 have been linked to various diseases, including neurodegenerative disorders, inflammatory conditions, and cancer.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Autophagy - animal

• Mitophagy

• Selective autophagy

• LC3-I to LC3-II conversion

• ATG5-ATG12 conjugation pathway

The ATG5 protein is a 275-amino acid protein that is essential for autophagy. It forms a covalent conjugate with ATG12 via a ubiquitin-like conjugation system, and this conjugate interacts with ATG16L1 to form a multimeric complex. This complex is required for the lipidation of LC3-I to LC3-II, which is a critical step in autophagosome membrane elongation and closure. ATG5 also has autophagy-independent functions, including roles in apoptosis, antigen presentation, and regulation of innate immune signaling. Its expression is ubiquitous, with higher levels in tissues with high metabolic activity. Mutations in ATG5 are rare but can cause severe neurological phenotypes when biallelic.