apl1
S. pombe
AP-2 adaptor complex subunit Apl1
What the model saw
Gene: apl1 Organism: Schizosaccharomyces pombe Known functions: AP-2 adaptor complex subunit Apl1. clathrin binding. clathrin-cargo adaptor activity.
View unredacted entry
AP-2 adaptor complex subunit Apl1. clathrin binding. clathrin-cargo adaptor activity.
Solver output
Apl1 is a subunit of the AP-2 adaptor complex, which mediates clathrin-coated vesicle formation at the plasma membrane for endocytosis. Clathrin-mediated endocytosis regulates the internalization and downregulation of surface receptors, including nutrient transporters and signaling receptors relevant to TOR pathway activity. While endocytosis is broadly important for cellular homeostasis, the specific role of AP-2/clathrin cargo adaptor activity in longevity is context-dependent: it could promote longevity by downregulating pro-growth signaling receptors (reducing TOR activity), or oppose it by removing nutrient transporters needed for stress responses. In S. pombe, the AP-2 complex is less central to endocytosis than in metazoans, further complicating the prediction. The net effect on longevity is genuinely ambiguous without direct experimental evidence.
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 "unclear" while the ground truth is "anti_longevity." The model's reasoning about AP-2/clathrin-mediated endocytosis and its potential connections to nutrient sensing and TOR signaling is plausible but speculative, and the model failed to commit to the correct direction. The model correctly identified the gene's molecular function (AP-2 adaptor complex, clathrin-mediated endocytosis) but could not determine the longevity influence. The mechanism class of "deregulated_nutrient_sensing" is a stretch - the more direct connection would be through endocytosis/membrane trafficking. The model's uncertainty was somewhat appropriate given limited direct evidence, but it missed the anti-longevity classification. Confidence of 0.35 reflects genuine uncertainty but the answer is still wrong.
Raw API responses
solver
{
"reasoning": "Apl1 is a subunit of the AP-2 adaptor complex, which mediates clathrin-coated vesicle formation at the plasma membrane for endocytosis. Clathrin-mediated endocytosis regulates the internalization and downregulation of surface receptors, including nutrient transporters and signaling receptors relevant to TOR pathway activity. While endocytosis is broadly important for cellular homeostasis, the specific role of AP-2/clathrin cargo adaptor activity in longevity is context-dependent: it could promote longevity by downregulating pro-growth signaling receptors (reducing TOR activity), or oppose it by removing nutrient transporters needed for stress responses. In S. pombe, the AP-2 complex is less central to endocytosis than in metazoans, further complicating the prediction. The net effect on longevity is genuinely ambiguous without direct experimental evidence.",
"confidence": 0.35,
"key_pathways": [
"clathrin-mediated endocytosis",
"AP-2 adaptor complex assembly",
"receptor internalization and nutrient sensing"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" while the ground truth is \"anti_longevity.\" The model's reasoning about AP-2/clathrin-mediated endocytosis and its potential connections to nutrient sensing and TOR signaling is plausible but speculative, and the model failed to commit to the correct direction. The model correctly identified the gene's molecular function (AP-2 adaptor complex, clathrin-mediated endocytosis) but could not determine the longevity influence. The mechanism class of \"deregulated_nutrient_sensing\" is a stretch - the more direct connection would be through endocytosis/membrane trafficking. The model's uncertainty was somewhat appropriate given limited direct evidence, but it missed the anti-longevity classification. Confidence of 0.35 reflects genuine uncertainty but the answer is still wrong.",
"failure_mode": "appropriately_uncertain",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}