Atg5
M. musculus
autophagy related 5
What the model saw
Gene: Atg5 Organism: Mus musculus Known functions: autophagy related 5. autophagy protein 5. Atg8-family ligase activity. protein binding.
View unredacted entry
autophagy related 5. autophagy protein 5. Atg8-family ligase activity. protein binding.
Solver output
ATG5 is a core component of the autophagy machinery, functioning as part of the ATG12–ATG5–ATG16L1 E3-like ligase complex that catalyzes the lipidation of ATG8-family proteins (e.g., LC3) onto the phagophore membrane, a critical step in autophagosome biogenesis. This Atg8-family ligase activity is essential for the elongation and closure of the autophagosome. Macroautophagy declines with age, and this decline is a recognized hallmark of aging; loss of ATG5 function in mice leads to accelerated aging phenotypes, while overexpression of ATG5 extends lifespan in mice. By enabling the clearance of damaged proteins and organelles, ATG5 directly opposes the accumulation of cellular damage associated with aging, placing it firmly in the pro-longevity category.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model correctly predicted pro_longevity for Atg5 in Mus musculus with high confidence (0.92). The mechanistic reasoning is excellent and accurate: ATG5 functions as part of the ATG12-ATG5-ATG16L1 E3-like ligase complex, catalyzes LC3 lipidation, is essential for autophagosome biogenesis, and its overexpression extends lifespan in mice while loss leads to accelerated aging. All key pathways identified are correct and relevant. The model correctly cited the known experimental evidence (overexpression extends lifespan, knockout accelerates aging).
Raw API responses
solver
{
"reasoning": "ATG5 is a core component of the autophagy machinery, functioning as part of the ATG12–ATG5–ATG16L1 E3-like ligase complex that catalyzes the lipidation of ATG8-family proteins (e.g., LC3) onto the phagophore membrane, a critical step in autophagosome biogenesis. This Atg8-family ligase activity is essential for the elongation and closure of the autophagosome. Macroautophagy declines with age, and this decline is a recognized hallmark of aging; loss of ATG5 function in mice leads to accelerated aging phenotypes, while overexpression of ATG5 extends lifespan in mice. By enabling the clearance of damaged proteins and organelles, ATG5 directly opposes the accumulation of cellular damage associated with aging, placing it firmly in the pro-longevity category.",
"confidence": 0.92,
"key_pathways": [
"macroautophagy / autophagosome biogenesis",
"ATG12-ATG5-ATG16L1 E3-like ligase complex",
"LC3 lipidation (ATG8 conjugation to PE)"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Atg5 in Mus musculus with high confidence (0.92). The mechanistic reasoning is excellent and accurate: ATG5 functions as part of the ATG12-ATG5-ATG16L1 E3-like ligase complex, catalyzes LC3 lipidation, is essential for autophagosome biogenesis, and its overexpression extends lifespan in mice while loss leads to accelerated aging. All key pathways identified are correct and relevant. The model correctly cited the known experimental evidence (overexpression extends lifespan, knockout accelerates aging).",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}