ipgm-1
C. elegans
2,3-bisphosphoglycerate-independent phosphoglycerate mutase
What the model saw
Gene: ipgm-1 Organism: Caenorhabditis elegans Known functions: 2,3-bisphosphoglycerate-independent phosphoglycerate mutase. catalytic activity. manganese ion binding. metal ion binding. phosphoglycerate mutase activity.
View unredacted entry
2,3-bisphosphoglycerate-independent phosphoglycerate mutase. catalytic activity. manganese ion binding. metal ion binding. phosphoglycerate mutase activity.
Solver output
ipgm-1 encodes a 2,3-bisphosphoglycerate-independent phosphoglycerate mutase (iPGM), which catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate in glycolysis. In C. elegans, iPGM-1 is an essential glycolytic enzyme, and its activity directly supports cellular energy metabolism and metabolic flux through glycolysis. Glycolytic rate and metabolic efficiency are tightly linked to nutrient-sensing pathways (insulin/IGF-1, AMPK, mTOR) that are central regulators of longevity in C. elegans. RNAi knockdown of ipgm-1 has been shown to reduce worm lifespan, indicating that its normal function is required for healthy aging. The manganese ion binding activity is consistent with the cofactor requirement of iPGM enzymes and supports proper catalytic function. Loss of this enzyme impairs energy homeostasis, consistent with a pro-longevity role for its normal, intact function.
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 that "RNAi knockdown of ipgm-1 has been shown to reduce worm lifespan" would actually support a pro_longevity classification if true, but the ground truth says anti_longevity, meaning that normal ipgm-1 function actually shortens lifespan (i.e., loss/reduction of ipgm-1 extends lifespan). The model's mechanistic reasoning is internally consistent but factually incorrect about the direction of the effect. The model was fairly confident (0.72) in the wrong direction. The mechanism class of "deregulated_nutrient_sensing" is also questionable for a core glycolytic enzyme - the primary mechanism would be glycolytic/metabolic rather than nutrient sensing per se. The model's claim about RNAi knockdown reducing lifespan appears to be fabricated or incorrect, as the actual data supports the opposite conclusion (knockdown extends lifespan, making ipgm-1 anti-longevity).
Raw API responses
solver
{
"reasoning": "ipgm-1 encodes a 2,3-bisphosphoglycerate-independent phosphoglycerate mutase (iPGM), which catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate in glycolysis. In C. elegans, iPGM-1 is an essential glycolytic enzyme, and its activity directly supports cellular energy metabolism and metabolic flux through glycolysis. Glycolytic rate and metabolic efficiency are tightly linked to nutrient-sensing pathways (insulin/IGF-1, AMPK, mTOR) that are central regulators of longevity in C. elegans. RNAi knockdown of ipgm-1 has been shown to reduce worm lifespan, indicating that its normal function is required for healthy aging. The manganese ion binding activity is consistent with the cofactor requirement of iPGM enzymes and supports proper catalytic function. Loss of this enzyme impairs energy homeostasis, consistent with a pro-longevity role for its normal, intact function.",
"confidence": 0.72,
"key_pathways": [
"glycolysis / phosphoglycerate interconversion",
"energy homeostasis and nutrient sensing",
"insulin/IGF-1 signaling longevity 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 that \"RNAi knockdown of ipgm-1 has been shown to reduce worm lifespan\" would actually support a pro_longevity classification if true, but the ground truth says anti_longevity, meaning that normal ipgm-1 function actually shortens lifespan (i.e., loss/reduction of ipgm-1 extends lifespan). The model's mechanistic reasoning is internally consistent but factually incorrect about the direction of the effect. The model was fairly confident (0.72) in the wrong direction. The mechanism class of \"deregulated_nutrient_sensing\" is also questionable for a core glycolytic enzyme - the primary mechanism would be glycolytic/metabolic rather than nutrient sensing per se. The model's claim about RNAi knockdown reducing lifespan appears to be fabricated or incorrect, as the actual data supports the opposite conclusion (knockdown extends lifespan, making ipgm-1 anti-longevity).",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}