aps2
S. pombe
AP-2 adaptor complex subunit Aps2
What the model saw
Gene: aps2 Organism: Schizosaccharomyces pombe Known functions: AP-2 adaptor complex subunit Aps2. clathrin-cargo adaptor activity.
View unredacted entry
AP-2 adaptor complex subunit Aps2. clathrin-cargo adaptor activity.
Solver output
Aps2 is the sigma subunit of the AP-2 adaptor complex, which mediates clathrin-dependent endocytosis by linking cargo membrane proteins to clathrin-coated vesicles at the plasma membrane. While endocytosis is essential for receptor downregulation and nutrient transporter trafficking, its net effect on longevity is context-dependent: it can promote longevity by downregulating growth-promoting receptors (e.g., reducing TORC1 signaling inputs) or oppose it by removing stress-response or autophagy-related receptors. In S. pombe, AP-2-mediated endocytosis is less well characterized than in mammals, and the specific cargo repertoire of Aps2 is not defined by these annotations alone. The clathrin-cargo adaptor function does not map cleanly to a single pro- or anti-longevity mechanism without knowledge of which receptors or transporters are preferentially internalized.
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 the bidirectional nature of endocytosis is plausible in general, but it failed to commit to the correct answer. The mechanism class chosen ("altered_intercellular_communication") is also questionable for a clathrin-mediated endocytosis gene — this would more appropriately fall under intracellular trafficking or signal transduction. The model's uncertainty was not well-calibrated given that GenAge has a clear anti_longevity designation for this gene. The reasoning, while not entirely wrong in its biological framing, led to an incorrect prediction with low confidence (0.35), which is a failure to correctly identify the longevity influence.
Raw API responses
solver
{
"reasoning": "Aps2 is the sigma subunit of the AP-2 adaptor complex, which mediates clathrin-dependent endocytosis by linking cargo membrane proteins to clathrin-coated vesicles at the plasma membrane. While endocytosis is essential for receptor downregulation and nutrient transporter trafficking, its net effect on longevity is context-dependent: it can promote longevity by downregulating growth-promoting receptors (e.g., reducing TORC1 signaling inputs) or oppose it by removing stress-response or autophagy-related receptors. In S. pombe, AP-2-mediated endocytosis is less well characterized than in mammals, and the specific cargo repertoire of Aps2 is not defined by these annotations alone. The clathrin-cargo adaptor function does not map cleanly to a single pro- or anti-longevity mechanism without knowledge of which receptors or transporters are preferentially internalized.",
"confidence": 0.35,
"key_pathways": [
"clathrin-mediated endocytosis",
"receptor downregulation",
"nutrient transporter trafficking"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" while the ground truth is \"anti_longevity.\" The model's reasoning about the bidirectional nature of endocytosis is plausible in general, but it failed to commit to the correct answer. The mechanism class chosen (\"altered_intercellular_communication\") is also questionable for a clathrin-mediated endocytosis gene — this would more appropriately fall under intracellular trafficking or signal transduction. The model's uncertainty was not well-calibrated given that GenAge has a clear anti_longevity designation for this gene. The reasoning, while not entirely wrong in its biological framing, led to an incorrect prediction with low confidence (0.35), which is a failure to correctly identify the longevity influence.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}