asb-1
C. elegans
ATP synthase F(0) complex subunit B1, mitochondrial
What the model saw
Gene: asb-1 Organism: Caenorhabditis elegans Known functions: ATP synthase F(0) complex subunit B1, mitochondrial. proton transmembrane transporter activity. proton-transporting ATP synthase activity, rotational mechanism.
View unredacted entry
ATP synthase F(0) complex subunit B1, mitochondrial. proton transmembrane transporter activity. proton-transporting ATP synthase activity, rotational mechanism.
Solver output
asb-1 encodes the F(0) subunit B1 of the mitochondrial ATP synthase (Complex V), which is essential for the rotational mechanism coupling proton translocation across the inner mitochondrial membrane to ATP synthesis. In C. elegans, partial loss-of-function of mitochondrial electron transport chain and ATP synthase subunits (e.g., isp-1, clk-1, nuo-6) is well-established to extend lifespan via mild mitochondrial stress signaling, including the mitochondrial unfolded protein response (UPRmt) and reduced reactive oxygen species production. However, the normal function of asb-1 is to maintain efficient oxidative phosphorylation and ATP production, which supports cellular energy homeostasis and proteostasis. Organisms with fully functional ATP synthase maintain mitochondrial membrane potential and efficient energy metabolism, which are hallmarks of healthy aging. The pro-longevity prediction reflects that the intact gene supports mitochondrial function, preventing the mitochondrial dysfunction hallmark of aging, though the nuance in C. elegans is that mild reduction can also extend life.
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 actually acknowledges the well-established C. elegans paradigm that partial loss-of-function of mitochondrial ATP synthase subunits extends lifespan (e.g., isp-1, clk-1, nuo-6), which is precisely why asb-1 is classified as anti_longevity — its normal function opposes longevity. The model then contradicts itself by concluding pro_longevity, arguing that the intact gene "supports mitochondrial function" and "prevents mitochondrial dysfunction." This is mechanistically confused: in C. elegans, the anti_longevity classification for ATP synthase subunits typically means that the gene's normal activity shortens lifespan (i.e., knockdown extends life). The model recognized the relevant biology but drew the wrong conclusion, assigning pro_longevity with 0.72 confidence when the correct answer is anti_longevity.
Raw API responses
solver
{
"reasoning": "asb-1 encodes the F(0) subunit B1 of the mitochondrial ATP synthase (Complex V), which is essential for the rotational mechanism coupling proton translocation across the inner mitochondrial membrane to ATP synthesis. In C. elegans, partial loss-of-function of mitochondrial electron transport chain and ATP synthase subunits (e.g., isp-1, clk-1, nuo-6) is well-established to extend lifespan via mild mitochondrial stress signaling, including the mitochondrial unfolded protein response (UPRmt) and reduced reactive oxygen species production. However, the normal function of asb-1 is to maintain efficient oxidative phosphorylation and ATP production, which supports cellular energy homeostasis and proteostasis. Organisms with fully functional ATP synthase maintain mitochondrial membrane potential and efficient energy metabolism, which are hallmarks of healthy aging. The pro-longevity prediction reflects that the intact gene supports mitochondrial function, preventing the mitochondrial dysfunction hallmark of aging, though the nuance in C. elegans is that mild reduction can also extend life.",
"confidence": 0.72,
"key_pathways": [
"oxidative phosphorylation / ATP synthesis (Complex V)",
"mitochondrial proton gradient maintenance",
"mitochondrial unfolded protein response (UPRmt)"
],
"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 actually acknowledges the well-established C. elegans paradigm that partial loss-of-function of mitochondrial ATP synthase subunits extends lifespan (e.g., isp-1, clk-1, nuo-6), which is precisely why asb-1 is classified as anti_longevity — its normal function opposes longevity. The model then contradicts itself by concluding pro_longevity, arguing that the intact gene \"supports mitochondrial function\" and \"prevents mitochondrial dysfunction.\" This is mechanistically confused: in C. elegans, the anti_longevity classification for ATP synthase subunits typically means that the gene's normal activity shortens lifespan (i.e., knockdown extends life). The model recognized the relevant biology but drew the wrong conclusion, assigning pro_longevity with 0.72 confidence when the correct answer is anti_longevity.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}