apl3
S. pombe
AP-2 adaptor complex subunit Alp3
What the model saw
Gene: apl3 Organism: Schizosaccharomyces pombe Known functions: AP-2 adaptor complex subunit Alp3. clathrin-cargo adaptor activity.
View unredacted entry
AP-2 adaptor complex subunit Alp3. clathrin-cargo adaptor activity.
Solver output
Apl3 is the alpha subunit of the AP-2 adaptor complex, which mediates clathrin-cargo adaptor activity at the plasma membrane to facilitate clathrin-mediated endocytosis. Efficient endocytosis is required for proper receptor downregulation, nutrient sensing, and membrane homeostasis. In yeast, endocytic trafficking intersects with autophagy and vacuolar/lysosomal degradation pathways; impaired endocytosis can disrupt proteostasis and vesicular trafficking to the vacuole. By enabling proper cargo sorting and internalization, apl3 supports the cell's ability to recycle membrane proteins and maintain proteostatic balance, which is generally associated with healthy aging. Loss of clathrin-mediated endocytosis components has been linked to impaired autophagy flux and accelerated cellular aging in model organisms.
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 reasoned that apl3 supports healthy aging by enabling proper endocytosis and proteostasis, but the actual finding is that apl3 is anti-longevity (meaning its loss or reduction extends lifespan, or its presence shortens lifespan). The mechanistic reasoning is speculative and incorrect in direction - the model assumed that because endocytosis is generally beneficial, apl3 must be pro-longevity, but in S. pombe this gene actually has an anti-longevity effect. The confidence was moderate (0.55) but still wrong. The reasoning quality is poor because it relied on general assumptions rather than specific evidence about apl3's role in S. pombe aging.
Raw API responses
solver
{
"reasoning": "Apl3 is the alpha subunit of the AP-2 adaptor complex, which mediates clathrin-cargo adaptor activity at the plasma membrane to facilitate clathrin-mediated endocytosis. Efficient endocytosis is required for proper receptor downregulation, nutrient sensing, and membrane homeostasis. In yeast, endocytic trafficking intersects with autophagy and vacuolar/lysosomal degradation pathways; impaired endocytosis can disrupt proteostasis and vesicular trafficking to the vacuole. By enabling proper cargo sorting and internalization, apl3 supports the cell's ability to recycle membrane proteins and maintain proteostatic balance, which is generally associated with healthy aging. Loss of clathrin-mediated endocytosis components has been linked to impaired autophagy flux and accelerated cellular aging in model organisms.",
"confidence": 0.55,
"key_pathways": [
"clathrin-mediated endocytosis",
"AP-2 complex vesicular trafficking",
"vacuolar/lysosomal proteostasis"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model reasoned that apl3 supports healthy aging by enabling proper endocytosis and proteostasis, but the actual finding is that apl3 is anti-longevity (meaning its loss or reduction extends lifespan, or its presence shortens lifespan). The mechanistic reasoning is speculative and incorrect in direction - the model assumed that because endocytosis is generally beneficial, apl3 must be pro-longevity, but in S. pombe this gene actually has an anti-longevity effect. The confidence was moderate (0.55) but still wrong. The reasoning quality is poor because it relied on general assumptions rather than specific evidence about apl3's role in S. pombe aging.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}