daf-9
C. elegans
3-ketosteroid oxygenase;Cytochrome P450
What the model saw
Gene: daf-9 Organism: Caenorhabditis elegans Known functions: 3-ketosteroid oxygenase;Cytochrome P450. heme binding. iron ion binding. monooxygenase activity. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen. steroid hydroxylase activity.
View unredacted entry
3-ketosteroid oxygenase;Cytochrome P450. heme binding. iron ion binding. monooxygenase activity. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen. steroid hydroxylase activity.
Solver output
DAF-9 is a cytochrome P450 enzyme (CYP22A1) that catalyzes the biosynthesis of dafachronic acids (DAs), the endogenous steroid hormone ligands for the nuclear receptor DAF-12 in C. elegans. By producing dafachronic acids, DAF-9 activates DAF-12 signaling, which integrates with the insulin/IGF-1 (DAF-2/DAF-16) and TGF-β pathways to regulate dauer formation and adult longevity. Active DAF-9/DAF-12 signaling (in the presence of ligand) promotes reproductive growth and suppresses dauer entry, but critically, DAF-9 activity is required for the ligand-bound DAF-12 to modulate downstream transcriptional programs that extend lifespan under certain conditions. Loss of daf-9 leads to constitutive dauer-like states and altered lipid/steroid metabolism, while its normal function in steroid hormone biosynthesis is essential for proper nutrient-sensing axis coordination. The steroid hormone axis governed by DAF-9 is a conserved nutrient-sensing mechanism linking metabolic state to longevity regulation.
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 0.85 confidence, but the ground truth is anti_longevity. DAF-9 produces dafachronic acids that activate DAF-12 in its ligand-bound form, which promotes reproductive growth and suppresses dauer entry — this is actually the anti-longevity direction. Loss of daf-9 (or reduced DAF-9 activity) leads to dauer-like states and extended lifespan, making daf-9 anti-longevity. The model correctly identified the biochemical mechanism (DAF-9 as a cytochrome P450 producing dafachronic acids for DAF-12 signaling) but drew the wrong conclusion about its longevity influence. The model acknowledged that DAF-9/DAF-12 signaling "promotes reproductive growth and suppresses dauer entry" but then incorrectly concluded this makes it pro-longevity. In fact, suppressing dauer entry and promoting reproduction is the anti-longevity direction in C. elegans. The mechanistic description is partially correct but the interpretation of its effect on longevity is inverted.
Raw API responses
solver
{
"reasoning": "DAF-9 is a cytochrome P450 enzyme (CYP22A1) that catalyzes the biosynthesis of dafachronic acids (DAs), the endogenous steroid hormone ligands for the nuclear receptor DAF-12 in C. elegans. By producing dafachronic acids, DAF-9 activates DAF-12 signaling, which integrates with the insulin/IGF-1 (DAF-2/DAF-16) and TGF-β pathways to regulate dauer formation and adult longevity. Active DAF-9/DAF-12 signaling (in the presence of ligand) promotes reproductive growth and suppresses dauer entry, but critically, DAF-9 activity is required for the ligand-bound DAF-12 to modulate downstream transcriptional programs that extend lifespan under certain conditions. Loss of daf-9 leads to constitutive dauer-like states and altered lipid/steroid metabolism, while its normal function in steroid hormone biosynthesis is essential for proper nutrient-sensing axis coordination. The steroid hormone axis governed by DAF-9 is a conserved nutrient-sensing mechanism linking metabolic state to longevity regulation.",
"confidence": 0.85,
"key_pathways": [
"dafachronic acid biosynthesis / DAF-12 nuclear receptor signaling",
"insulin/IGF-1 longevity pathway (DAF-2/DAF-16)",
"dauer formation and lifespan regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity with 0.85 confidence, but the ground truth is anti_longevity. DAF-9 produces dafachronic acids that activate DAF-12 in its ligand-bound form, which promotes reproductive growth and suppresses dauer entry — this is actually the anti-longevity direction. Loss of daf-9 (or reduced DAF-9 activity) leads to dauer-like states and extended lifespan, making daf-9 anti-longevity. The model correctly identified the biochemical mechanism (DAF-9 as a cytochrome P450 producing dafachronic acids for DAF-12 signaling) but drew the wrong conclusion about its longevity influence. The model acknowledged that DAF-9/DAF-12 signaling \"promotes reproductive growth and suppresses dauer entry\" but then incorrectly concluded this makes it pro-longevity. In fact, suppressing dauer entry and promoting reproduction is the anti-longevity direction in C. elegans. The mechanistic description is partially correct but the interpretation of its effect on longevity is inverted.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}