InR
D. melanogaster
Insulin-like receptor
What the model saw
Gene: InR Organism: Drosophila melanogaster Known functions: Insulin-like receptor. ATP binding. identical protein binding. insulin binding. insulin receptor activity. insulin receptor substrate binding. phosphatidylinositol 3-kinase binding. protein binding. protein kinase activity. protein tyrosine kinase activity. transmembrane receptor protein tyrosine kinase activity.
View unredacted entry
Insulin-like receptor. ATP binding. identical protein binding. insulin binding. insulin receptor activity. insulin receptor substrate binding. phosphatidylinositol 3-kinase binding. protein binding. protein kinase activity. protein tyrosine kinase activity. transmembrane receptor protein tyrosine kinase activity.
Solver output
InR encodes the Drosophila insulin-like receptor, a transmembrane receptor tyrosine kinase that initiates the insulin/IGF-1 signaling (IIS) pathway upon ligand binding. Activation of InR leads to phosphorylation of the insulin receptor substrate (chico in Drosophila), recruitment of PI3K, and downstream activation of Akt/PKB, which phosphorylates and cytoplasmatically sequesters the FOXO transcription factor dFOXO. Reduced InR activity (hypomorphic mutations or tissue-specific loss of function, particularly in the fat body) extends lifespan in Drosophila by allowing dFOXO nuclear translocation and upregulation of stress-resistance and proteostasis genes. Because reduced IIS signaling is one of the most robust pro-longevity interventions across model organisms, the normal (full) activity of InR promotes aging by suppressing dFOXO, making InR itself anti-longevity in its wild-type role. However, InR is classified as pro-longevity here because partial loss-of-function or reduced signaling through this receptor is the canonical lifespan-extending intervention — meaning the gene's reduced activity promotes longevity, and the receptor itself is the key node whose attenuation confers benefit. Consistent with the López-Otín framework, this falls squarely within deregulated nutrient sensing as the primary hallmark.
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 correctly understands the biology of InR: it's the Drosophila insulin receptor, and reduced IIS signaling extends lifespan. The model even explicitly states "the normal (full) activity of InR promotes aging by suppressing dFOXO, making InR itself anti-longevity in its wild-type role." This is the correct classification (anti_longevity), matching the ground truth. However, the model then contradicts itself and outputs "pro_longevity" as its final answer, with a confused justification that "reduced activity promotes longevity" means the gene is pro_longevity. This is a logical error: a gene whose reduction extends lifespan is classified as anti_longevity (its normal activity works against longevity). The model's mechanistic understanding is correct, but it applied the wrong classification logic and arrived at the wrong answer with high confidence (0.82). The reasoning quality is moderate — the model correctly describes the mechanism but then makes a classification error despite explicitly stating the correct interpretation mid-reasoning.
Raw API responses
solver
{
"reasoning": "InR encodes the Drosophila insulin-like receptor, a transmembrane receptor tyrosine kinase that initiates the insulin/IGF-1 signaling (IIS) pathway upon ligand binding. Activation of InR leads to phosphorylation of the insulin receptor substrate (chico in Drosophila), recruitment of PI3K, and downstream activation of Akt/PKB, which phosphorylates and cytoplasmatically sequesters the FOXO transcription factor dFOXO. Reduced InR activity (hypomorphic mutations or tissue-specific loss of function, particularly in the fat body) extends lifespan in Drosophila by allowing dFOXO nuclear translocation and upregulation of stress-resistance and proteostasis genes. Because reduced IIS signaling is one of the most robust pro-longevity interventions across model organisms, the normal (full) activity of InR promotes aging by suppressing dFOXO, making InR itself anti-longevity in its wild-type role. However, InR is classified as pro-longevity here because partial loss-of-function or reduced signaling through this receptor is the canonical lifespan-extending intervention — meaning the gene's reduced activity promotes longevity, and the receptor itself is the key node whose attenuation confers benefit. Consistent with the López-Otín framework, this falls squarely within deregulated nutrient sensing as the primary hallmark.",
"confidence": 0.82,
"key_pathways": [
"Insulin/IGF-1 signaling (IIS) pathway",
"PI3K-Akt-dFOXO axis",
"Nutrient sensing and TOR signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly understands the biology of InR: it's the Drosophila insulin receptor, and reduced IIS signaling extends lifespan. The model even explicitly states \"the normal (full) activity of InR promotes aging by suppressing dFOXO, making InR itself anti-longevity in its wild-type role.\" This is the correct classification (anti_longevity), matching the ground truth. However, the model then contradicts itself and outputs \"pro_longevity\" as its final answer, with a confused justification that \"reduced activity promotes longevity\" means the gene is pro_longevity. This is a logical error: a gene whose reduction extends lifespan is classified as anti_longevity (its normal activity works against longevity). The model's mechanistic understanding is correct, but it applied the wrong classification logic and arrived at the wrong answer with high confidence (0.82). The reasoning quality is moderate — the model correctly describes the mechanism but then makes a classification error despite explicitly stating the correct interpretation mid-reasoning.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}