ADE6
S. cerevisiae
phosphoribosylformylglycinamidine synthase
What the model saw
Gene: ADE6 Organism: Saccharomyces cerevisiae Known functions: phosphoribosylformylglycinamidine synthase. phosphoribosylformylglycinamidine synthase activity.
View unredacted entry
phosphoribosylformylglycinamidine synthase. phosphoribosylformylglycinamidine synthase activity.
Solver output
ADE6 encodes phosphoribosylformylglycinamidine (FGAM) synthase, which catalyzes the fourth step of the de novo purine biosynthesis pathway, converting FGAR to FGAM using glutamine as a nitrogen donor. Adequate purine (ATP/GTP) availability is essential for proper TORC1 signaling and nutrient sensing; purine limitation is a known signal that downregulates TORC1 activity in yeast, which is generally pro-longevity. Loss of de novo purine synthesis forces cells into purine auxotrophy, disrupting nucleotide pools and potentially impairing AMPK/TORC1 balance. Functional ADE6 thus supports balanced purine homeostasis, which is required for normal metabolic signaling and avoidance of the toxic SAICAR/AIR intermediate accumulation seen in ade mutants. Maintaining this pathway supports cellular energy charge and nucleotide-dependent regulation of aging-related kinases, placing its normal function on the pro-longevity side.
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." ADE6 is an anti-longevity gene in yeast, meaning its deletion extends lifespan. The model's reasoning is plausible on the surface (purine biosynthesis supporting TORC1 signaling and nucleotide homeostasis), but it reaches the wrong conclusion. In yeast, many ade mutants actually show extended chronological or replicative lifespan, possibly because purine limitation mimics caloric restriction or reduces TORC1 activity. The model's logic that "functional ADE6 supports pro-longevity signaling" is inverted — the actual finding is that ADE6 activity is anti-longevity (its loss promotes longevity). The model's confidence of 0.62 is moderate but still wrong. The mechanistic reasoning about TORC1 and purine sensing is speculative and leads to the incorrect conclusion.
Raw API responses
solver
{
"reasoning": "ADE6 encodes phosphoribosylformylglycinamidine (FGAM) synthase, which catalyzes the fourth step of the de novo purine biosynthesis pathway, converting FGAR to FGAM using glutamine as a nitrogen donor. Adequate purine (ATP/GTP) availability is essential for proper TORC1 signaling and nutrient sensing; purine limitation is a known signal that downregulates TORC1 activity in yeast, which is generally pro-longevity. Loss of de novo purine synthesis forces cells into purine auxotrophy, disrupting nucleotide pools and potentially impairing AMPK/TORC1 balance. Functional ADE6 thus supports balanced purine homeostasis, which is required for normal metabolic signaling and avoidance of the toxic SAICAR/AIR intermediate accumulation seen in ade mutants. Maintaining this pathway supports cellular energy charge and nucleotide-dependent regulation of aging-related kinases, placing its normal function on the pro-longevity side.",
"confidence": 0.62,
"key_pathways": [
"de novo purine biosynthesis",
"TORC1 nutrient sensing",
"nucleotide homeostasis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" ADE6 is an anti-longevity gene in yeast, meaning its deletion extends lifespan. The model's reasoning is plausible on the surface (purine biosynthesis supporting TORC1 signaling and nucleotide homeostasis), but it reaches the wrong conclusion. In yeast, many ade mutants actually show extended chronological or replicative lifespan, possibly because purine limitation mimics caloric restriction or reduces TORC1 activity. The model's logic that \"functional ADE6 supports pro-longevity signaling\" is inverted — the actual finding is that ADE6 activity is anti-longevity (its loss promotes longevity). The model's confidence of 0.62 is moderate but still wrong. The mechanistic reasoning about TORC1 and purine sensing is speculative and leads to the incorrect conclusion.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}