Pi3K92E
D. melanogaster
Phosphatidylinositol 3-kinase 92E
What the model saw
Gene: Pi3K92E Organism: Drosophila melanogaster Known functions: Phosphatidylinositol 3-kinase 92E. phosphatidylinositol 3-kinase 92E. 1-phosphatidylinositol-3-kinase activity. 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity. 1-phosphatidylinositol-4-phosphate 3-kinase activity. kinase activity.
View unredacted entry
Phosphatidylinositol 3-kinase 92E. phosphatidylinositol 3-kinase 92E. 1-phosphatidylinositol-3-kinase activity. 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity. 1-phosphatidylinositol-4-phosphate 3-kinase activity. kinase activity.
Solver output
Pi3K92E is the Drosophila ortholog of the catalytic subunit of Class I PI3K, which phosphorylates PIP2 to generate PIP3 at the plasma membrane. This is the central activating step of the insulin/IGF-1 signaling (IIS) pathway: PIP3 recruits and activates Akt/PKB, which in turn phosphorylates and inactivates the FOXO transcription factor (dFOXO in Drosophila). Reduced IIS/PI3K activity is one of the most robust pro-longevity interventions across model organisms, including Drosophila, where loss-of-function of chico (IRS), InR, or Pi3K92E extends lifespan. Conversely, the normal (wild-type) function of Pi3K92E is to drive IIS forward, suppressing dFOXO-mediated stress resistance and autophagy programs that promote longevity. Therefore, the normal activity of this kinase is anti-longevity.
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 anti_longevity but the ground truth is pro_longevity. The model's reasoning follows the standard IIS pathway logic (PI3K drives IIS, reduced IIS extends lifespan, therefore PI3K is anti-longevity), but this is incorrect for Pi3K92E in Drosophila. In reality, Pi3K92E (the Class I PI3K catalytic subunit) has been shown to have pro-longevity effects in Drosophila - likely because tissue-specific or moderate overexpression of PI3K activity (e.g., in neurons or fat body) can extend lifespan, or because the gene's role is more nuanced than simple IIS activation. The model's reasoning is internally consistent but applies a simplistic framework that doesn't match the actual experimental data. The model was highly confident (0.88) in the wrong answer. Notably, the model even mentions that loss-of-function of Pi3K92E extends lifespan, which would make the gene pro-longevity (since reducing it helps), yet then concludes the gene is anti-longevity - this is a logical inconsistency in the model's own reasoning about the GenAge classification convention.
Raw API responses
solver
{
"reasoning": "Pi3K92E is the Drosophila ortholog of the catalytic subunit of Class I PI3K, which phosphorylates PIP2 to generate PIP3 at the plasma membrane. This is the central activating step of the insulin/IGF-1 signaling (IIS) pathway: PIP3 recruits and activates Akt/PKB, which in turn phosphorylates and inactivates the FOXO transcription factor (dFOXO in Drosophila). Reduced IIS/PI3K activity is one of the most robust pro-longevity interventions across model organisms, including Drosophila, where loss-of-function of chico (IRS), InR, or Pi3K92E extends lifespan. Conversely, the normal (wild-type) function of Pi3K92E is to drive IIS forward, suppressing dFOXO-mediated stress resistance and autophagy programs that promote longevity. Therefore, the normal activity of this kinase is anti-longevity.",
"confidence": 0.88,
"key_pathways": [
"Insulin/IGF-1 signaling (IIS) pathway",
"PI3K-Akt-FOXO axis",
"TOR nutrient sensing"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity but the ground truth is pro_longevity. The model's reasoning follows the standard IIS pathway logic (PI3K drives IIS, reduced IIS extends lifespan, therefore PI3K is anti-longevity), but this is incorrect for Pi3K92E in Drosophila. In reality, Pi3K92E (the Class I PI3K catalytic subunit) has been shown to have pro-longevity effects in Drosophila - likely because tissue-specific or moderate overexpression of PI3K activity (e.g., in neurons or fat body) can extend lifespan, or because the gene's role is more nuanced than simple IIS activation. The model's reasoning is internally consistent but applies a simplistic framework that doesn't match the actual experimental data. The model was highly confident (0.88) in the wrong answer. Notably, the model even mentions that loss-of-function of Pi3K92E extends lifespan, which would make the gene pro-longevity (since reducing it helps), yet then concludes the gene is anti-longevity - this is a logical inconsistency in the model's own reasoning about the GenAge classification convention.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": true
}