IDP1
S. cerevisiae
isocitrate dehydrogenase (NADP(+)) IDP1
What the model saw
Gene: IDP1 Organism: Saccharomyces cerevisiae Known functions: isocitrate dehydrogenase (NADP(+)) IDP1. NAD binding. isocitrate dehydrogenase (NADP+) activity. magnesium ion binding. oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. protein binding.
View unredacted entry
isocitrate dehydrogenase (NADP(+)) IDP1. NAD binding. isocitrate dehydrogenase (NADP+) activity. magnesium ion binding. oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. protein binding.
Solver output
IDP1 encodes the mitochondrial NADP+-dependent isocitrate dehydrogenase in S. cerevisiae, which catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate in the TCA cycle while generating NADPH. Mitochondrial NADPH is a critical reducing equivalent used by glutathione reductase and thioredoxin systems to neutralize reactive oxygen species (ROS) within the mitochondrial matrix. Loss of IDP1 reduces mitochondrial NADPH pools, impairing antioxidant defenses and increasing oxidative damage to mitochondrial proteins, DNA, and lipids. Elevated mitochondrial ROS accelerates aging-associated mitochondrial dysfunction, a well-established hallmark of aging. Studies in yeast have shown that IDP1 deletion shortens chronological lifespan, consistent with its pro-longevity role through mitochondrial redox homeostasis.
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 mechanistic reasoning about IDP1's role in mitochondrial NADPH generation and ROS detoxification is plausible and partially correct in describing the gene's function, but the conclusion about longevity direction is wrong. The model claims "IDP1 deletion shortens chronological lifespan, consistent with its pro-longevity role" — but if deletion shortens lifespan, that means the gene's normal activity is pro-longevity, not anti-longevity. However, the ground truth says IDP1 is anti_longevity, meaning its presence/overexpression shortens lifespan or its deletion extends lifespan. The model's mechanistic reasoning actually contradicts the ground truth: if IDP1 deletion shortens lifespan (as the model claims), IDP1 would be pro_longevity, but GenAge classifies it as anti_longevity. This suggests either the model's factual claim about deletion effects is wrong, or there's complexity in the experimental data. The model was moderately confident (0.72) in the wrong direction. The reasoning quality is moderate — the biochemical logic is sound but the final conclusion and the cited experimental evidence appear to be incorrect or fabricated.
Raw API responses
solver
{
"reasoning": "IDP1 encodes the mitochondrial NADP+-dependent isocitrate dehydrogenase in S. cerevisiae, which catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate in the TCA cycle while generating NADPH. Mitochondrial NADPH is a critical reducing equivalent used by glutathione reductase and thioredoxin systems to neutralize reactive oxygen species (ROS) within the mitochondrial matrix. Loss of IDP1 reduces mitochondrial NADPH pools, impairing antioxidant defenses and increasing oxidative damage to mitochondrial proteins, DNA, and lipids. Elevated mitochondrial ROS accelerates aging-associated mitochondrial dysfunction, a well-established hallmark of aging. Studies in yeast have shown that IDP1 deletion shortens chronological lifespan, consistent with its pro-longevity role through mitochondrial redox homeostasis.",
"confidence": 0.72,
"key_pathways": [
"TCA cycle / mitochondrial NADPH generation",
"mitochondrial ROS detoxification (glutathione/thioredoxin systems)",
"oxidative stress response"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's mechanistic reasoning about IDP1's role in mitochondrial NADPH generation and ROS detoxification is plausible and partially correct in describing the gene's function, but the conclusion about longevity direction is wrong. The model claims \"IDP1 deletion shortens chronological lifespan, consistent with its pro-longevity role\" — but if deletion shortens lifespan, that means the gene's normal activity is pro-longevity, not anti-longevity. However, the ground truth says IDP1 is anti_longevity, meaning its presence/overexpression shortens lifespan or its deletion extends lifespan. The model's mechanistic reasoning actually contradicts the ground truth: if IDP1 deletion shortens lifespan (as the model claims), IDP1 would be pro_longevity, but GenAge classifies it as anti_longevity. This suggests either the model's factual claim about deletion effects is wrong, or there's complexity in the experimental data. The model was moderately confident (0.72) in the wrong direction. The reasoning quality is moderate — the biochemical logic is sound but the final conclusion and the cited experimental evidence appear to be incorrect or fabricated.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}