wah-1
C. elegans
Pyr_redox_2 domain-containing protein
What the model saw
Gene: wah-1 Organism: Caenorhabditis elegans Known functions: Pyr_redox_2 domain-containing protein. FAD binding. NAD(P)H oxidase H2O2-forming activity. enzyme binding. flavin adenine dinucleotide binding. oxidoreductase activity. protein dimerization activity.
View unredacted entry
Pyr_redox_2 domain-containing protein. FAD binding. NAD(P)H oxidase H2O2-forming activity. enzyme binding. flavin adenine dinucleotide binding. oxidoreductase activity. protein dimerization activity.
Solver output
wah-1 encodes a FAD-binding oxidoreductase with NAD(P)H oxidase H2O2-forming activity, placing it in the NADPH oxidase/flavoenzyme family that generates reactive oxygen species (ROS). In C. elegans, elevated H2O2 production from such enzymes increases oxidative stress burden, which is a well-established driver of mitochondrial dysfunction and accelerated aging. The Pyr_redox_2 domain is characteristic of pyridine nucleotide-disulfide oxidoreductases, and the H2O2-forming activity directly contributes to oxidative damage to macromolecules. While low-level ROS can act as signaling molecules (hormesis), constitutive H2O2 generation by this enzyme class is generally associated with pro-oxidant, pro-aging effects. Loss-of-function of ROS-generating enzymes in C. elegans typically extends lifespan, consistent with wah-1 normal function being anti-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 correctly predicted anti_longevity for wah-1, but the mechanistic reasoning is incorrect. wah-1 in C. elegans is actually the homolog of mammalian AIF (Apoptosis-Inducing Factor), a mitochondrial flavoprotein involved in apoptosis and mitochondrial function. The wah-1 gene is known to promote apoptosis and its loss extends lifespan in C. elegans through apoptosis-related mechanisms, not primarily through NADPH oxidase-mediated ROS generation as the model claimed. The model incorrectly categorized wah-1 as an NADPH oxidase/flavoenzyme that generates ROS to cause oxidative stress, when in reality it functions as an AIF homolog involved in apoptosis signaling. The Pyr_redox_2 domain is present in AIF proteins, but the model's interpretation of the mechanism was wrong. The correct answer was reached but for the wrong reasons.
Raw API responses
solver
{
"reasoning": "wah-1 encodes a FAD-binding oxidoreductase with NAD(P)H oxidase H2O2-forming activity, placing it in the NADPH oxidase/flavoenzyme family that generates reactive oxygen species (ROS). In C. elegans, elevated H2O2 production from such enzymes increases oxidative stress burden, which is a well-established driver of mitochondrial dysfunction and accelerated aging. The Pyr_redox_2 domain is characteristic of pyridine nucleotide-disulfide oxidoreductases, and the H2O2-forming activity directly contributes to oxidative damage to macromolecules. While low-level ROS can act as signaling molecules (hormesis), constitutive H2O2 generation by this enzyme class is generally associated with pro-oxidant, pro-aging effects. Loss-of-function of ROS-generating enzymes in C. elegans typically extends lifespan, consistent with wah-1 normal function being anti-longevity.",
"confidence": 0.72,
"key_pathways": [
"NAD(P)H oxidase / ROS generation",
"mitochondrial oxidative stress",
"redox homeostasis"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for wah-1, but the mechanistic reasoning is incorrect. wah-1 in C. elegans is actually the homolog of mammalian AIF (Apoptosis-Inducing Factor), a mitochondrial flavoprotein involved in apoptosis and mitochondrial function. The wah-1 gene is known to promote apoptosis and its loss extends lifespan in C. elegans through apoptosis-related mechanisms, not primarily through NADPH oxidase-mediated ROS generation as the model claimed. The model incorrectly categorized wah-1 as an NADPH oxidase/flavoenzyme that generates ROS to cause oxidative stress, when in reality it functions as an AIF homolog involved in apoptosis signaling. The Pyr_redox_2 domain is present in AIF proteins, but the model's interpretation of the mechanism was wrong. The correct answer was reached but for the wrong reasons.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}