atg20
S. pombe
sorting nexin Atg20
What the model saw
Gene: atg20 Organism: Schizosaccharomyces pombe Known functions: sorting nexin Atg20. phosphatidylinositol binding. phosphatidylinositol-3-phosphate binding. protein binding.
View unredacted entry
sorting nexin Atg20. phosphatidylinositol binding. phosphatidylinositol-3-phosphate binding. protein binding.
Solver output
Atg20 is a sorting nexin with a PX domain that binds phosphatidylinositol-3-phosphate (PI3P), a lipid generated by the autophagy-specific PI3-kinase complex (Vps34/Atg14). In yeast, Atg20 functions as part of the Atg17-Atg29-Atg31 scaffold or the Atg1 complex periphery, and its PI3P-binding activity is required for proper recruitment to the phagophore assembly site (PAS), facilitating autophagosome nucleation and cargo recognition. Loss of Atg20 impairs selective and non-selective autophagy flux, leading to accumulation of damaged proteins and organelles. Since functional macroautophagy is a well-established pro-longevity pathway in yeast and other model organisms, the normal activity of Atg20 in supporting autophagy initiation promotes lifespan extension.
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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumes that because Atg20 supports autophagy, its loss would impair autophagy and reduce lifespan, making it pro_longevity. However, the GenAge database classifies atg20 as anti_longevity in S. pombe, meaning its presence/activity shortens lifespan (or its deletion extends lifespan). This is counterintuitive to the model's autophagy-promotes-longevity framework. The model was fairly confident (0.75) in the wrong direction. The mechanistic reasoning about Atg20's role in PI3P binding and autophagy is generally plausible for the gene's molecular function, but the conclusion about longevity influence is incorrect. In S. pombe, the relationship between autophagy genes and chronological lifespan can be complex and sometimes opposite to what's seen in S. cerevisiae or C. elegans.
Raw API responses
solver
{
"reasoning": "Atg20 is a sorting nexin with a PX domain that binds phosphatidylinositol-3-phosphate (PI3P), a lipid generated by the autophagy-specific PI3-kinase complex (Vps34/Atg14). In yeast, Atg20 functions as part of the Atg17-Atg29-Atg31 scaffold or the Atg1 complex periphery, and its PI3P-binding activity is required for proper recruitment to the phagophore assembly site (PAS), facilitating autophagosome nucleation and cargo recognition. Loss of Atg20 impairs selective and non-selective autophagy flux, leading to accumulation of damaged proteins and organelles. Since functional macroautophagy is a well-established pro-longevity pathway in yeast and other model organisms, the normal activity of Atg20 in supporting autophagy initiation promotes lifespan extension.",
"confidence": 0.75,
"key_pathways": [
"macroautophagy / autophagosome nucleation",
"PI3P signaling at the phagophore assembly site",
"selective autophagy cargo recognition"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumes that because Atg20 supports autophagy, its loss would impair autophagy and reduce lifespan, making it pro_longevity. However, the GenAge database classifies atg20 as anti_longevity in S. pombe, meaning its presence/activity shortens lifespan (or its deletion extends lifespan). This is counterintuitive to the model's autophagy-promotes-longevity framework. The model was fairly confident (0.75) in the wrong direction. The mechanistic reasoning about Atg20's role in PI3P binding and autophagy is generally plausible for the gene's molecular function, but the conclusion about longevity influence is incorrect. In S. pombe, the relationship between autophagy genes and chronological lifespan can be complex and sometimes opposite to what's seen in S. cerevisiae or C. elegans.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}