aps-1
C. elegans
AP complex subunit sigma
What the model saw
Gene: aps-1 Organism: Caenorhabditis elegans Known functions: AP complex subunit sigma. clathrin-cargo adaptor activity.
View unredacted entry
AP complex subunit sigma. clathrin-cargo adaptor activity.
Solver output
APS-1 is the sigma subunit of the AP (adaptor protein) complex, which mediates clathrin-dependent endocytosis and intracellular vesicle trafficking by linking cargo proteins to clathrin-coated vesicles. While proper endocytic trafficking is essential for receptor downregulation (e.g., DAF-2/insulin receptor internalization, which could modulate IIS/DAF-16 signaling and longevity), the AP complex also supports nutrient uptake, lysosomal targeting, and intercellular signaling broadly. Loss of AP complex function in C. elegans has been linked to altered DAF-2 trafficking, which could extend lifespan via reduced insulin signaling, but the sigma subunit's role is structural/accessory and its perturbation could disrupt multiple trafficking routes with opposing effects on longevity. The net effect on lifespan is therefore difficult to predict from molecular function alone without direct genetic 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" with low confidence (0.35), but the ground truth is "anti_longevity" - meaning aps-1 promotes longevity when lost/inhibited (i.e., it acts against longevity). The model's reasoning was overly hedged and failed to commit to a direction. The model did mention that loss of AP complex function could extend lifespan via reduced insulin signaling (DAF-2 trafficking), which is directionally consistent with the anti_longevity classification, but it ultimately concluded the effect was unclear rather than anti-longevity. The mechanistic reasoning about DAF-2/insulin receptor trafficking is plausible but not definitively correct. The model's failure to commit to a prediction when there were reasonable mechanistic clues pointing toward anti-longevity is a notable shortcoming.
Raw API responses
solver
{
"reasoning": "APS-1 is the sigma subunit of the AP (adaptor protein) complex, which mediates clathrin-dependent endocytosis and intracellular vesicle trafficking by linking cargo proteins to clathrin-coated vesicles. While proper endocytic trafficking is essential for receptor downregulation (e.g., DAF-2/insulin receptor internalization, which could modulate IIS/DAF-16 signaling and longevity), the AP complex also supports nutrient uptake, lysosomal targeting, and intercellular signaling broadly. Loss of AP complex function in C. elegans has been linked to altered DAF-2 trafficking, which could extend lifespan via reduced insulin signaling, but the sigma subunit's role is structural/accessory and its perturbation could disrupt multiple trafficking routes with opposing effects on longevity. The net effect on lifespan is therefore difficult to predict from molecular function alone without direct genetic evidence.",
"confidence": 0.35,
"key_pathways": [
"clathrin-mediated endocytosis",
"insulin/IGF-1 signaling (DAF-2 receptor trafficking)",
"lysosomal cargo sorting"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" with low confidence (0.35), but the ground truth is \"anti_longevity\" - meaning aps-1 promotes longevity when lost/inhibited (i.e., it acts against longevity). The model's reasoning was overly hedged and failed to commit to a direction. The model did mention that loss of AP complex function could extend lifespan via reduced insulin signaling (DAF-2 trafficking), which is directionally consistent with the anti_longevity classification, but it ultimately concluded the effect was unclear rather than anti-longevity. The mechanistic reasoning about DAF-2/insulin receptor trafficking is plausible but not definitively correct. The model's failure to commit to a prediction when there were reasonable mechanistic clues pointing toward anti-longevity is a notable shortcoming.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}