ZTA1
S. cerevisiae
NADPH:quinone reductase
What the model saw
Gene: ZTA1 Organism: Saccharomyces cerevisiae Known functions: NADPH:quinone reductase. 2-alkenal reductase [NAD(P)H] activity. mRNA 3'-UTR AU-rich region binding. oxidoreductase activity. quinone reductase (NADPH) activity. zinc ion binding.
View unredacted entry
NADPH:quinone reductase. 2-alkenal reductase [NAD(P)H] activity. mRNA 3'-UTR AU-rich region binding. oxidoreductase activity. quinone reductase (NADPH) activity. zinc ion binding.
Solver output
ZTA1 encodes an NADPH:quinone reductase and 2-alkenal reductase in S. cerevisiae. Its primary role is the two-electron reduction of quinones to hydroquinones (via NADPH), which prevents one-electron redox cycling of quinones that would otherwise generate reactive oxygen species (ROS) and cause oxidative damage. Additionally, its 2-alkenal reductase activity detoxifies reactive lipid peroxidation byproducts (e.g., 4-hydroxynonenal, acrolein), which are hallmarks of oxidative stress and lipid peroxidation. By suppressing both quinone-mediated ROS generation and lipid aldehyde toxicity, ZTA1 reduces mitochondrial and cellular oxidative damage. The zinc ion binding likely supports structural integrity of the active site. Collectively, this detoxification function is expected to extend replicative or chronological lifespan by mitigating oxidative stress, a well-established driver of aging in yeast.
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 with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — quinone reductases and alkenal reductases do detoxify reactive species — but it reached the wrong conclusion. In yeast, ZTA1 deletion or overexpression studies apparently show it has an anti-longevity effect, meaning the gene promotes aging rather than extending lifespan. The model's mechanistic reasoning about ROS suppression and oxidative stress mitigation is logically coherent but does not match the actual experimental outcome. The model was fairly confident (0.72) in its wrong answer. The mechanism class of 'mitochondrial_dysfunction' is also not well-supported by the gene's known functions, which are primarily cytosolic detoxification activities.
Raw API responses
solver
{
"reasoning": "ZTA1 encodes an NADPH:quinone reductase and 2-alkenal reductase in S. cerevisiae. Its primary role is the two-electron reduction of quinones to hydroquinones (via NADPH), which prevents one-electron redox cycling of quinones that would otherwise generate reactive oxygen species (ROS) and cause oxidative damage. Additionally, its 2-alkenal reductase activity detoxifies reactive lipid peroxidation byproducts (e.g., 4-hydroxynonenal, acrolein), which are hallmarks of oxidative stress and lipid peroxidation. By suppressing both quinone-mediated ROS generation and lipid aldehyde toxicity, ZTA1 reduces mitochondrial and cellular oxidative damage. The zinc ion binding likely supports structural integrity of the active site. Collectively, this detoxification function is expected to extend replicative or chronological lifespan by mitigating oxidative stress, a well-established driver of aging in yeast.",
"confidence": 0.72,
"key_pathways": [
"NADPH-dependent quinone detoxification / ROS suppression",
"lipid peroxidation byproduct (2-alkenal) detoxification",
"oxidative stress response"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — quinone reductases and alkenal reductases do detoxify reactive species — but it reached the wrong conclusion. In yeast, ZTA1 deletion or overexpression studies apparently show it has an anti-longevity effect, meaning the gene promotes aging rather than extending lifespan. The model's mechanistic reasoning about ROS suppression and oxidative stress mitigation is logically coherent but does not match the actual experimental outcome. The model was fairly confident (0.72) in its wrong answer. The mechanism class of 'mitochondrial_dysfunction' is also not well-supported by the gene's known functions, which are primarily cytosolic detoxification activities.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}