Thor
D. melanogaster
thor
What the model saw
Gene: Thor Organism: Drosophila melanogaster Known functions: thor. eukaryotic initiation factor 4E binding. protein binding. translation repressor activity.
View unredacted entry
thor. eukaryotic initiation factor 4E binding. protein binding. translation repressor activity.
Solver output
Thor is the Drosophila ortholog of 4E-BP1 (eIF4E-binding protein 1), a key downstream effector of the TOR (Target of Rapamycin) nutrient-sensing pathway. Under nutrient-limiting or low-TOR-activity conditions, Thor/4E-BP1 is hypophosphorylated and binds eIF4E, sequestering it and repressing cap-dependent translation. This translational repression mimics the effects of dietary restriction and reduced insulin/TOR signaling, both of which are well-established pro-longevity interventions in Drosophila. Overexpression of Thor has been shown to extend lifespan in flies, consistent with its role as a translational brake downstream of TOR. By inhibiting eIF4E-mediated translation initiation, Thor reduces global protein synthesis rates, which alleviates proteotoxic stress and conserves cellular resources, contributing to 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 correctly identified Thor as pro_longevity with high confidence (0.88). The mechanistic reasoning is excellent: Thor is indeed the Drosophila 4E-BP1 ortholog, it acts downstream of TOR signaling, its overexpression extends lifespan in flies, and the explanation of how eIF4E sequestration leads to translational repression mimicking dietary restriction is accurate and well-supported by the literature. All key pathways identified are relevant and correct.
Raw API responses
solver
{
"reasoning": "Thor is the Drosophila ortholog of 4E-BP1 (eIF4E-binding protein 1), a key downstream effector of the TOR (Target of Rapamycin) nutrient-sensing pathway. Under nutrient-limiting or low-TOR-activity conditions, Thor/4E-BP1 is hypophosphorylated and binds eIF4E, sequestering it and repressing cap-dependent translation. This translational repression mimics the effects of dietary restriction and reduced insulin/TOR signaling, both of which are well-established pro-longevity interventions in Drosophila. Overexpression of Thor has been shown to extend lifespan in flies, consistent with its role as a translational brake downstream of TOR. By inhibiting eIF4E-mediated translation initiation, Thor reduces global protein synthesis rates, which alleviates proteotoxic stress and conserves cellular resources, contributing to longevity.",
"confidence": 0.88,
"key_pathways": [
"insulin/TOR signaling",
"cap-dependent translation initiation (eIF4E inhibition)",
"dietary restriction response"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified Thor as pro_longevity with high confidence (0.88). The mechanistic reasoning is excellent: Thor is indeed the Drosophila 4E-BP1 ortholog, it acts downstream of TOR signaling, its overexpression extends lifespan in flies, and the explanation of how eIF4E sequestration leads to translational repression mimicking dietary restriction is accurate and well-supported by the literature. All key pathways identified are relevant and correct.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}