VBA5
S. cerevisiae
basic amino acid transporter
What the model saw
Gene: VBA5 Organism: Saccharomyces cerevisiae Known functions: basic amino acid transporter. transmembrane transporter activity.
View unredacted entry
basic amino acid transporter. transmembrane transporter activity.
Solver output
VBA5 encodes a vacuolar basic amino acid transporter in S. cerevisiae, mediating transmembrane transport of basic amino acids (lysine, arginine, histidine) across the vacuolar membrane. Amino acid availability in the vacuole/cytoplasm can influence TORC1 signaling, as amino acid sensing is a key upstream input to TOR complex 1, which is a central regulator of longevity. However, the directionality of VBA5's effect on longevity is ambiguous: sequestering basic amino acids into the vacuole could dampen TORC1 activity (pro-longevity) or, conversely, releasing them could support anabolic processes. The functional annotation alone does not specify whether VBA5 imports or exports amino acids relative to the vacuolar lumen, nor does it indicate the net effect on cytoplasmic amino acid pools and TORC1 activity. Without additional evidence on transport directionality and its downstream consequences on nutrient sensing, a confident prediction cannot be made.
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." The model's reasoning about TORC1 amino acid sensing is plausible but speculative, and the model explicitly declined to commit to a direction. The mechanistic reasoning is not confirmed as correct either. The model's uncertainty was somewhat reasonable given limited information, but it still failed to identify the correct anti-longevity classification. The reasoning quality is modest — the TORC1 connection is a reasonable hypothesis but the model couldn't resolve directionality, which is the key issue.
Raw API responses
solver
{
"reasoning": "VBA5 encodes a vacuolar basic amino acid transporter in S. cerevisiae, mediating transmembrane transport of basic amino acids (lysine, arginine, histidine) across the vacuolar membrane. Amino acid availability in the vacuole/cytoplasm can influence TORC1 signaling, as amino acid sensing is a key upstream input to TOR complex 1, which is a central regulator of longevity. However, the directionality of VBA5's effect on longevity is ambiguous: sequestering basic amino acids into the vacuole could dampen TORC1 activity (pro-longevity) or, conversely, releasing them could support anabolic processes. The functional annotation alone does not specify whether VBA5 imports or exports amino acids relative to the vacuolar lumen, nor does it indicate the net effect on cytoplasmic amino acid pools and TORC1 activity. Without additional evidence on transport directionality and its downstream consequences on nutrient sensing, a confident prediction cannot be made.",
"confidence": 0.35,
"key_pathways": [
"TORC1 amino acid sensing",
"vacuolar amino acid storage",
"basic amino acid transmembrane transport"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" with low confidence (0.35), but the ground truth is \"anti_longevity.\" The model's reasoning about TORC1 amino acid sensing is plausible but speculative, and the model explicitly declined to commit to a direction. The mechanistic reasoning is not confirmed as correct either. The model's uncertainty was somewhat reasonable given limited information, but it still failed to identify the correct anti-longevity classification. The reasoning quality is modest — the TORC1 connection is a reasonable hypothesis but the model couldn't resolve directionality, which is the key issue.",
"failure_mode": "appropriately_uncertain",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}