ImpL2
D. melanogaster
Ecdysone-inducible gene L2
What the model saw
Gene: ImpL2 Organism: Drosophila melanogaster Known functions: Ecdysone-inducible gene L2. cell-cell adhesion mediator activity. insulin binding.
View unredacted entry
Ecdysone-inducible gene L2. cell-cell adhesion mediator activity. insulin binding.
Solver output
ImpL2 (Imaginal morphogenesis protein Late 2) is a Drosophila homolog of vertebrate IGFBP7 (insulin-like growth factor binding protein 7) and functions as a secreted antagonist of insulin/IGF signaling (IIS) by directly binding insulin-like peptides and sequestering them from their receptor. Reduced IIS through the InR/PI3K/Akt/FOXO axis is one of the most robust pro-longevity interventions across model organisms, including Drosophila. By binding and inhibiting insulin-like peptides, ImpL2 dampens IIS, which promotes nuclear localization of the FOXO transcription factor dFOXO, upregulating stress resistance and longevity genes. Overexpression of ImpL2 in specific tissues (e.g., gut tumors or muscle) has been shown to extend lifespan in some contexts by systemically reducing IIS. Its ecdysone-inducible nature also links it to developmental and metabolic regulation, consistent with a role in nutrient-sensing modulation.
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 predicted ImpL2 as pro_longevity with high confidence (0.78). The mechanistic reasoning is excellent and accurate: ImpL2 is indeed a Drosophila IGFBP7 homolog that sequesters insulin-like peptides, dampens IIS, promotes dFOXO nuclear localization, and extends lifespan. The model correctly identifies the key pathways involved and even mentions the tissue-specific overexpression contexts (gut tumors, muscle) that have been shown to extend lifespan. The mechanism class of "deregulated_nutrient_sensing" is appropriate. Overall, this is a well-reasoned, accurate prediction.
Raw API responses
solver
{
"reasoning": "ImpL2 (Imaginal morphogenesis protein Late 2) is a Drosophila homolog of vertebrate IGFBP7 (insulin-like growth factor binding protein 7) and functions as a secreted antagonist of insulin/IGF signaling (IIS) by directly binding insulin-like peptides and sequestering them from their receptor. Reduced IIS through the InR/PI3K/Akt/FOXO axis is one of the most robust pro-longevity interventions across model organisms, including Drosophila. By binding and inhibiting insulin-like peptides, ImpL2 dampens IIS, which promotes nuclear localization of the FOXO transcription factor dFOXO, upregulating stress resistance and longevity genes. Overexpression of ImpL2 in specific tissues (e.g., gut tumors or muscle) has been shown to extend lifespan in some contexts by systemically reducing IIS. Its ecdysone-inducible nature also links it to developmental and metabolic regulation, consistent with a role in nutrient-sensing modulation.",
"confidence": 0.78,
"key_pathways": [
"insulin/IGF signaling (IIS) pathway",
"dFOXO transcription factor activation",
"insulin-like peptide sequestration"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted ImpL2 as pro_longevity with high confidence (0.78). The mechanistic reasoning is excellent and accurate: ImpL2 is indeed a Drosophila IGFBP7 homolog that sequesters insulin-like peptides, dampens IIS, promotes dFOXO nuclear localization, and extends lifespan. The model correctly identifies the key pathways involved and even mentions the tissue-specific overexpression contexts (gut tumors, muscle) that have been shown to extend lifespan. The mechanism class of \"deregulated_nutrient_sensing\" is appropriate. Overall, this is a well-reasoned, accurate prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}