asb-2
C. elegans
ATP synthase F(0) complex subunit B2, mitochondrial
What the model saw
Gene: asb-2 Organism: Caenorhabditis elegans Known functions: ATP synthase F(0) complex subunit B2, mitochondrial. proton transmembrane transporter activity. proton-transporting ATP synthase activity, rotational mechanism.
View unredacted entry
ATP synthase F(0) complex subunit B2, mitochondrial. proton transmembrane transporter activity. proton-transporting ATP synthase activity, rotational mechanism.
Solver output
asb-2 encodes a subunit of the mitochondrial ATP synthase F(0) complex (subunit B2), which is essential for the rotational mechanism of proton-transporting ATP synthase (Complex V). In C. elegans, partial loss-of-function of mitochondrial electron transport chain and ATP synthase components — particularly F(0) subunits — is well-documented to extend lifespan, likely through mild mitochondrial uncoupling, reduced ROS production, or activation of mitohormesis signaling. The proton transmembrane transporter activity of this subunit is central to the proton gradient-driven rotation that synthesizes ATP; its normal function sustains full mitochondrial respiration. Paradoxically, full ATP synthase activity is associated with higher metabolic rate and shorter lifespan in C. elegans, while reduced activity (e.g., via RNAi of isp-1, clk-1, or atp subunits) extends lifespan. Therefore, the normal (wild-type) function of asb-2 in maintaining robust ATP synthesis is more consistent with a pro-longevity role when present at physiological levels, supporting mitochondrial homeostasis, though the relationship is nuanced given that partial reduction also extends 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 is internally contradictory and ultimately arrives at the wrong conclusion. The model correctly identifies that partial loss-of-function of ATP synthase subunits in C. elegans extends lifespan (which is well-established), but then incorrectly concludes that the normal function of asb-2 is "pro_longevity." If reducing asb-2 activity extends lifespan, then the gene's normal function is anti_longevity (it works against longevity when present). The model even acknowledges this paradox but fails to draw the correct conclusion from its own reasoning. The mechanism class of "mitochondrial_dysfunction" is also somewhat misleading — the correct framing would be that normal asb-2 function promotes ATP synthesis which is associated with shorter lifespan, making it anti_longevity. The model's confidence of 0.62 is moderate but still wrong.
Raw API responses
solver
{
"reasoning": "asb-2 encodes a subunit of the mitochondrial ATP synthase F(0) complex (subunit B2), which is essential for the rotational mechanism of proton-transporting ATP synthase (Complex V). In C. elegans, partial loss-of-function of mitochondrial electron transport chain and ATP synthase components — particularly F(0) subunits — is well-documented to extend lifespan, likely through mild mitochondrial uncoupling, reduced ROS production, or activation of mitohormesis signaling. The proton transmembrane transporter activity of this subunit is central to the proton gradient-driven rotation that synthesizes ATP; its normal function sustains full mitochondrial respiration. Paradoxically, full ATP synthase activity is associated with higher metabolic rate and shorter lifespan in C. elegans, while reduced activity (e.g., via RNAi of isp-1, clk-1, or atp subunits) extends lifespan. Therefore, the normal (wild-type) function of asb-2 in maintaining robust ATP synthesis is more consistent with a pro-longevity role when present at physiological levels, supporting mitochondrial homeostasis, though the relationship is nuanced given that partial reduction also extends life.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial oxidative phosphorylation (Complex V / ATP synthase)",
"proton motive force and mitohormesis signaling",
"mitochondrial energy homeostasis"
],
"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 arrives at the wrong conclusion. The model correctly identifies that partial loss-of-function of ATP synthase subunits in C. elegans extends lifespan (which is well-established), but then incorrectly concludes that the normal function of asb-2 is \"pro_longevity.\" If reducing asb-2 activity extends lifespan, then the gene's normal function is anti_longevity (it works against longevity when present). The model even acknowledges this paradox but fails to draw the correct conclusion from its own reasoning. The mechanism class of \"mitochondrial_dysfunction\" is also somewhat misleading — the correct framing would be that normal asb-2 function promotes ATP synthesis which is associated with shorter lifespan, making it anti_longevity. The model's confidence of 0.62 is moderate but still wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}