c47e12.2
C. elegans
ADP/ATP translocase
What the model saw
Gene: C47E12.2 Organism: Caenorhabditis elegans Known functions: ADP/ATP translocase. ATP:ADP antiporter activity.
View unredacted entry
ADP/ATP translocase. ATP:ADP antiporter activity.
Solver output
C47E12.2 encodes an ADP/ATP translocase (adenine nucleotide translocator, ANT), which catalyzes the electrogenic exchange of mitochondrial ATP for cytosolic ADP across the inner mitochondrial membrane. This is the rate-limiting step coupling oxidative phosphorylation to cellular energy demand. In C. elegans, mild impairment of mitochondrial electron transport chain and ATP synthesis components (e.g., via RNAi knockdown) is well-documented to extend lifespan through reduced mitochondrial membrane potential, decreased reactive oxygen species production, and activation of mitochondrial stress responses (UPRmt). Loss or reduction of ANT activity can paradoxically reduce mitochondrial ROS output and activate compensatory longevity pathways. However, the normal function of ANT is to sustain efficient mitochondrial ATP export; its presence supports mitochondrial integrity, and complete loss is lethal. The net prediction leans pro-longevity for the normal gene function, as efficient mitochondrial energy coupling is associated with healthier mitochondria and reduced oxidative damage over time, though the relationship is nuanced given that partial ANT reduction extends lifespan in multiple models.
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 is internally contradictory and ultimately reaches the wrong conclusion. It correctly identifies that partial ANT reduction can extend lifespan in C. elegans (which would make the gene anti_longevity - i.e., its presence/normal function opposes longevity), but then concludes the gene is pro_longevity by arguing that efficient mitochondrial energy coupling is associated with healthier mitochondria. The model essentially argues both sides and picks the wrong one. An ADP/ATP translocase that, when reduced/knocked down, extends lifespan would be classified as anti_longevity (its normal function works against longevity), which matches the ground truth. The model had the right mechanistic information but drew the wrong conclusion from it.
Raw API responses
solver
{
"reasoning": "C47E12.2 encodes an ADP/ATP translocase (adenine nucleotide translocator, ANT), which catalyzes the electrogenic exchange of mitochondrial ATP for cytosolic ADP across the inner mitochondrial membrane. This is the rate-limiting step coupling oxidative phosphorylation to cellular energy demand. In C. elegans, mild impairment of mitochondrial electron transport chain and ATP synthesis components (e.g., via RNAi knockdown) is well-documented to extend lifespan through reduced mitochondrial membrane potential, decreased reactive oxygen species production, and activation of mitochondrial stress responses (UPRmt). Loss or reduction of ANT activity can paradoxically reduce mitochondrial ROS output and activate compensatory longevity pathways. However, the normal function of ANT is to sustain efficient mitochondrial ATP export; its presence supports mitochondrial integrity, and complete loss is lethal. The net prediction leans pro-longevity for the normal gene function, as efficient mitochondrial energy coupling is associated with healthier mitochondria and reduced oxidative damage over time, though the relationship is nuanced given that partial ANT reduction extends lifespan in multiple models.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial ATP/ADP exchange (oxidative phosphorylation coupling)",
"mitochondrial unfolded protein response (UPRmt)",
"reactive oxygen species signaling"
],
"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 reasoning is internally contradictory and ultimately reaches the wrong conclusion. It correctly identifies that partial ANT reduction can extend lifespan in C. elegans (which would make the gene anti_longevity - i.e., its presence/normal function opposes longevity), but then concludes the gene is pro_longevity by arguing that efficient mitochondrial energy coupling is associated with healthier mitochondria. The model essentially argues both sides and picks the wrong one. An ADP/ATP translocase that, when reduced/knocked down, extends lifespan would be classified as anti_longevity (its normal function works against longevity), which matches the ground truth. The model had the right mechanistic information but drew the wrong conclusion from it.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}