Eps8
M. musculus
epidermal growth factor receptor pathway substrate 8
What the model saw
Gene: Eps8 Organism: Mus musculus Known functions: epidermal growth factor receptor pathway substrate 8. epidermal growth factor receptor kinase substrate 8. actin binding. protein binding. small GTPase binding.
View unredacted entry
epidermal growth factor receptor pathway substrate 8. epidermal growth factor receptor kinase substrate 8. actin binding. protein binding. small GTPase binding.
Solver output
Eps8 (Epidermal Growth Factor Receptor Pathway Substrate 8) is a substrate of the EGFR kinase that modulates downstream signaling through its actin-binding and small GTPase-binding activities. Notably, Eps8 knockout mice have been shown to be long-lived and lean, suggesting that Eps8 normally amplifies EGFR/Ras/PI3K signaling — a pathway closely related to the IGF-1/insulin axis that is a central regulator of aging. By binding small GTPases (e.g., Rac1) and acting as a scaffold in growth factor receptor signaling, Eps8 promotes anabolic, pro-growth signaling that, when absent, mimics the longevity-extending effects of reduced nutrient/growth factor sensing. Its actin-remodeling role downstream of Rac1 also connects it to cytoskeletal dynamics that influence cellular homeostasis. Loss of Eps8 thus recapitulates the pro-longevity phenotype of attenuated growth factor signaling, meaning its normal function 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's mechanistic reasoning is actually correct and well-articulated: Eps8 knockout mice are long-lived, meaning Eps8's normal function is anti-longevity. The model correctly identifies this in its reasoning ("meaning its normal function is anti-longevity"). However, the model then contradicts itself by outputting "pro_longevity" as the longevity_influence label, when the correct answer is "anti_longevity." This is a self-contradictory prediction where the reasoning leads to the right conclusion but the final answer field is wrong. The model essentially reasoned correctly but then labeled the gene incorrectly — it confused the direction of the label. The gene promotes aging (anti_longevity), but the model labeled it pro_longevity despite explicitly stating in its reasoning that "its normal function is anti-longevity."
Raw API responses
solver
{
"reasoning": "Eps8 (Epidermal Growth Factor Receptor Pathway Substrate 8) is a substrate of the EGFR kinase that modulates downstream signaling through its actin-binding and small GTPase-binding activities. Notably, Eps8 knockout mice have been shown to be long-lived and lean, suggesting that Eps8 normally amplifies EGFR/Ras/PI3K signaling — a pathway closely related to the IGF-1/insulin axis that is a central regulator of aging. By binding small GTPases (e.g., Rac1) and acting as a scaffold in growth factor receptor signaling, Eps8 promotes anabolic, pro-growth signaling that, when absent, mimics the longevity-extending effects of reduced nutrient/growth factor sensing. Its actin-remodeling role downstream of Rac1 also connects it to cytoskeletal dynamics that influence cellular homeostasis. Loss of Eps8 thus recapitulates the pro-longevity phenotype of attenuated growth factor signaling, meaning its normal function is anti-longevity.",
"confidence": 0.62,
"key_pathways": [
"EGFR/Ras/PI3K growth factor signaling",
"small GTPase (Rac1) signaling and actin remodeling",
"IGF-1/insulin-like nutrient sensing axis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model's mechanistic reasoning is actually correct and well-articulated: Eps8 knockout mice are long-lived, meaning Eps8's normal function is anti-longevity. The model correctly identifies this in its reasoning (\"meaning its normal function is anti-longevity\"). However, the model then contradicts itself by outputting \"pro_longevity\" as the longevity_influence label, when the correct answer is \"anti_longevity.\" This is a self-contradictory prediction where the reasoning leads to the right conclusion but the final answer field is wrong. The model essentially reasoned correctly but then labeled the gene incorrectly — it confused the direction of the label. The gene promotes aging (anti_longevity), but the model labeled it pro_longevity despite explicitly stating in its reasoning that \"its normal function is anti-longevity.\"",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}