mboa-1
C. elegans
O-acyltransferase
What the model saw
Gene: mboa-1 Organism: Caenorhabditis elegans Known functions: O-acyltransferase. O-acyltransferase activity. cholesterol O-acyltransferase activity. sterol O-acyltransferase activity.
View unredacted entry
O-acyltransferase. O-acyltransferase activity. cholesterol O-acyltransferase activity. sterol O-acyltransferase activity.
Solver output
mboa-1 encodes a sterol/cholesterol O-acyltransferase (ACAT-like enzyme) in C. elegans, which esterifies free cholesterol and sterols for storage in lipid droplets. Elevated sterol esterification activity promotes lipid storage and shifts sterol homeostasis away from signaling-competent free cholesterol pools. In C. elegans, sterol metabolism is tightly linked to nutrient-sensing pathways, including DAF-2/insulin-IGF-1 signaling and DAF-16/FOXO regulation; excess lipid storage driven by ACAT activity is generally associated with reduced lifespan. In mammals, ACAT inhibition is known to reduce lipid accumulation and improve metabolic outcomes, and analogous logic applies in worms where reduced lipid esterification correlates with pro-longevity states. Thus, the normal function of mboa-1 in promoting cholesterol esterification and lipid storage is predicted to oppose longevity by dysregulating sterol-dependent nutrient sensing.
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 anti_longevity but the ground truth is pro_longevity. The model's reasoning was based on an analogy to mammalian ACAT biology and assumed that cholesterol esterification promotes lipid storage and reduces lifespan. However, in C. elegans, mboa-1 appears to be pro-longevity, suggesting the model's mechanistic reasoning was also incorrect. The model was moderately confident (0.65) in the wrong direction. The reasoning about DAF-2/insulin-IGF-1 and DAF-16/FOXO pathways was speculative and not grounded in actual C. elegans mboa-1 data.
Raw API responses
solver
{
"reasoning": "mboa-1 encodes a sterol/cholesterol O-acyltransferase (ACAT-like enzyme) in C. elegans, which esterifies free cholesterol and sterols for storage in lipid droplets. Elevated sterol esterification activity promotes lipid storage and shifts sterol homeostasis away from signaling-competent free cholesterol pools. In C. elegans, sterol metabolism is tightly linked to nutrient-sensing pathways, including DAF-2/insulin-IGF-1 signaling and DAF-16/FOXO regulation; excess lipid storage driven by ACAT activity is generally associated with reduced lifespan. In mammals, ACAT inhibition is known to reduce lipid accumulation and improve metabolic outcomes, and analogous logic applies in worms where reduced lipid esterification correlates with pro-longevity states. Thus, the normal function of mboa-1 in promoting cholesterol esterification and lipid storage is predicted to oppose longevity by dysregulating sterol-dependent nutrient sensing.",
"confidence": 0.65,
"key_pathways": [
"sterol/cholesterol esterification and lipid droplet storage",
"DAF-2/insulin-IGF-1 nutrient sensing",
"DAF-16/FOXO transcriptional regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity but the ground truth is pro_longevity. The model's reasoning was based on an analogy to mammalian ACAT biology and assumed that cholesterol esterification promotes lipid storage and reduces lifespan. However, in C. elegans, mboa-1 appears to be pro-longevity, suggesting the model's mechanistic reasoning was also incorrect. The model was moderately confident (0.65) in the wrong direction. The reasoning about DAF-2/insulin-IGF-1 and DAF-16/FOXO pathways was speculative and not grounded in actual C. elegans mboa-1 data.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}