fbp-1
C. elegans
Fructose-1,6-bisphosphatase isozyme 2
What the model saw
Gene: fbp-1 Organism: Caenorhabditis elegans Known functions: Fructose-1,6-bisphosphatase isozyme 2. fructose 1,6-bisphosphate 1-phosphatase activity. phosphatase activity. phosphoric ester hydrolase activity.
View unredacted entry
Fructose-1,6-bisphosphatase isozyme 2. fructose 1,6-bisphosphate 1-phosphatase activity. phosphatase activity. phosphoric ester hydrolase activity.
Solver output
Fructose-1,6-bisphosphatase (FBPase) catalyzes the irreversible hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate, a key rate-limiting step in gluconeogenesis. By promoting gluconeogenesis and opposing glycolytic flux, fbp-1 activity reduces glucose availability and mimics a low-glucose/caloric restriction state. In C. elegans, reduced glucose signaling is well-established to extend lifespan through activation of AMPK and FOXO/DAF-16 transcription factor pathways, and suppression of insulin/IGF-1 signaling. Elevated gluconeogenic capacity via FBPase activity thus shifts nutrient sensing toward a longevity-promoting metabolic state. Additionally, gluconeogenesis supports trehalose synthesis in C. elegans, which is linked to stress resistance and 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 pro_longevity but the ground truth is anti_longevity. The model's reasoning was plausible-sounding but ultimately incorrect. While the biochemical description of FBPase activity is accurate (gluconeogenesis, fructose-1,6-bisphosphate hydrolysis), the model's inference that this would promote longevity via caloric restriction mimicry is wrong. In C. elegans, fbp-1 is actually anti-longevity, meaning its activity shortens lifespan rather than extending it. The model constructed a coherent but incorrect mechanistic narrative, with moderate-high confidence (0.72), making this a confident wrong prediction. The reasoning about glucose restriction mimicry and AMPK/DAF-16 activation was speculative and not supported by the actual experimental evidence for this gene.
Raw API responses
solver
{
"reasoning": "Fructose-1,6-bisphosphatase (FBPase) catalyzes the irreversible hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate, a key rate-limiting step in gluconeogenesis. By promoting gluconeogenesis and opposing glycolytic flux, fbp-1 activity reduces glucose availability and mimics a low-glucose/caloric restriction state. In C. elegans, reduced glucose signaling is well-established to extend lifespan through activation of AMPK and FOXO/DAF-16 transcription factor pathways, and suppression of insulin/IGF-1 signaling. Elevated gluconeogenic capacity via FBPase activity thus shifts nutrient sensing toward a longevity-promoting metabolic state. Additionally, gluconeogenesis supports trehalose synthesis in C. elegans, which is linked to stress resistance and longevity.",
"confidence": 0.72,
"key_pathways": [
"gluconeogenesis / glucose restriction mimicry",
"insulin/IGF-1 signaling (DAF-2/DAF-16 axis)",
"AMPK nutrient sensing pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning was plausible-sounding but ultimately incorrect. While the biochemical description of FBPase activity is accurate (gluconeogenesis, fructose-1,6-bisphosphate hydrolysis), the model's inference that this would promote longevity via caloric restriction mimicry is wrong. In C. elegans, fbp-1 is actually anti-longevity, meaning its activity shortens lifespan rather than extending it. The model constructed a coherent but incorrect mechanistic narrative, with moderate-high confidence (0.72), making this a confident wrong prediction. The reasoning about glucose restriction mimicry and AMPK/DAF-16 activation was speculative and not supported by the actual experimental evidence for this gene.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}