JhI-21
D. melanogaster
Juvenile hormone Inducible-21
What the model saw
Gene: JhI-21 Organism: Drosophila melanogaster Known functions: Juvenile hormone Inducible-21. juvenile hormone Inducible-21. L-amino acid transmembrane transporter activity. transmembrane transporter activity. transporter activator activity.
View unredacted entry
Juvenile hormone Inducible-21. juvenile hormone Inducible-21. L-amino acid transmembrane transporter activity. transmembrane transporter activity. transporter activator activity.
Solver output
JhI-21 encodes a juvenile hormone-inducible L-amino acid transmembrane transporter in Drosophila. L-amino acid transporters directly regulate intracellular amino acid availability, which is a key upstream input to the TOR (Target of Rapamycin) nutrient-sensing pathway. By facilitating amino acid import, JhI-21 can modulate TORC1 activity; however, its induction by juvenile hormone (JH) links it to the insulin/IGF-like signaling (IIS) and JH endocrine axes, both of which are central regulators of Drosophila lifespan. Reduced JH signaling is associated with extended lifespan in Drosophila, and JhI-21 as a JH-inducible transporter may mediate amino acid-dependent anabolic signaling downstream of JH. Proper amino acid transport is also essential for proteostasis and tissue maintenance, suggesting that balanced transporter activity supports healthspan. Loss or overactivation of amino acid transport affecting TOR signaling can be detrimental, but the native pro-nutrient-sensing role of JhI-21 under JH control suggests it broadly supports organismal growth and metabolic homeostasis, with a net pro-longevity effect when functioning normally to maintain amino acid balance.
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's reasoning is speculative and ultimately leads to the wrong conclusion. While the model correctly identifies relevant pathways (JH signaling, TOR/nutrient sensing, IIS), it incorrectly reasons that JhI-21's role as an amino acid transporter would be net pro-longevity. In reality, JhI-21 is anti-longevity, which is consistent with the known fact that JH signaling generally promotes aging/reduces lifespan in Drosophila, and that enhanced amino acid transport/TOR activation is typically anti-longevity. The model even acknowledges that reduced JH signaling extends lifespan, yet still concludes JhI-21 is pro-longevity - an internal contradiction in its reasoning. The confidence of 0.65 is moderate but still represents a wrong prediction with flawed mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "JhI-21 encodes a juvenile hormone-inducible L-amino acid transmembrane transporter in Drosophila. L-amino acid transporters directly regulate intracellular amino acid availability, which is a key upstream input to the TOR (Target of Rapamycin) nutrient-sensing pathway. By facilitating amino acid import, JhI-21 can modulate TORC1 activity; however, its induction by juvenile hormone (JH) links it to the insulin/IGF-like signaling (IIS) and JH endocrine axes, both of which are central regulators of Drosophila lifespan. Reduced JH signaling is associated with extended lifespan in Drosophila, and JhI-21 as a JH-inducible transporter may mediate amino acid-dependent anabolic signaling downstream of JH. Proper amino acid transport is also essential for proteostasis and tissue maintenance, suggesting that balanced transporter activity supports healthspan. Loss or overactivation of amino acid transport affecting TOR signaling can be detrimental, but the native pro-nutrient-sensing role of JhI-21 under JH control suggests it broadly supports organismal growth and metabolic homeostasis, with a net pro-longevity effect when functioning normally to maintain amino acid balance.",
"confidence": 0.65,
"key_pathways": [
"L-amino acid transport / TOR nutrient sensing",
"Juvenile hormone signaling",
"Insulin/IGF-like signaling (IIS)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is speculative and ultimately leads to the wrong conclusion. While the model correctly identifies relevant pathways (JH signaling, TOR/nutrient sensing, IIS), it incorrectly reasons that JhI-21's role as an amino acid transporter would be net pro-longevity. In reality, JhI-21 is anti-longevity, which is consistent with the known fact that JH signaling generally promotes aging/reduces lifespan in Drosophila, and that enhanced amino acid transport/TOR activation is typically anti-longevity. The model even acknowledges that reduced JH signaling extends lifespan, yet still concludes JhI-21 is pro-longevity - an internal contradiction in its reasoning. The confidence of 0.65 is moderate but still represents a wrong prediction with flawed mechanistic reasoning.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}