PHO89
S. cerevisiae
Pho89p
What the model saw
Gene: PHO89 Organism: Saccharomyces cerevisiae Known functions: Pho89p. identical protein binding. phosphate transmembrane transporter activity. sodium:phosphate symporter activity.
View unredacted entry
Pho89p. identical protein binding. phosphate transmembrane transporter activity. sodium:phosphate symporter activity.
Solver output
PHO89 encodes a high-affinity Na⁺/phosphate symporter that imports inorganic phosphate into yeast cells under alkaline conditions. Elevated intracellular phosphate promotes activation of the TOR (Target of Rapamycin) signaling pathway, a central nutrient-sensing hub whose hyperactivation is well-established as anti-longevity in yeast and other organisms. Increased phosphate uptake via PHO89 would thus sustain or amplify TOR activity, suppressing autophagy and stress responses that are protective for lifespan. Consistent with this, mutations that reduce phosphate import or signaling through the PHO pathway (e.g., pho84 deletion) extend chronological and replicative lifespan in yeast. PHO89's role in driving phosphate accumulation therefore places it in the nutrient-sensing axis as a pro-aging factor.
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 correctly predicted PHO89 as anti_longevity. The mechanistic reasoning is plausible and well-constructed: PHO89 encodes a Na+/phosphate symporter, and elevated phosphate import can promote TOR signaling, which is a well-established anti-longevity pathway. The model also correctly draws the analogy to PHO84 (another phosphate transporter whose deletion extends lifespan). The reasoning is coherent and consistent with known yeast aging biology. Confidence of 0.65 is appropriately calibrated given the indirect nature of the evidence. The mechanism class of "deregulated_nutrient_sensing" is reasonable.
Raw API responses
solver
{
"reasoning": "PHO89 encodes a high-affinity Na⁺/phosphate symporter that imports inorganic phosphate into yeast cells under alkaline conditions. Elevated intracellular phosphate promotes activation of the TOR (Target of Rapamycin) signaling pathway, a central nutrient-sensing hub whose hyperactivation is well-established as anti-longevity in yeast and other organisms. Increased phosphate uptake via PHO89 would thus sustain or amplify TOR activity, suppressing autophagy and stress responses that are protective for lifespan. Consistent with this, mutations that reduce phosphate import or signaling through the PHO pathway (e.g., pho84 deletion) extend chronological and replicative lifespan in yeast. PHO89's role in driving phosphate accumulation therefore places it in the nutrient-sensing axis as a pro-aging factor.",
"confidence": 0.65,
"key_pathways": [
"PHO pathway (phosphate sensing)",
"TOR signaling / nutrient sensing",
"sodium-phosphate symport"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted PHO89 as anti_longevity. The mechanistic reasoning is plausible and well-constructed: PHO89 encodes a Na+/phosphate symporter, and elevated phosphate import can promote TOR signaling, which is a well-established anti-longevity pathway. The model also correctly draws the analogy to PHO84 (another phosphate transporter whose deletion extends lifespan). The reasoning is coherent and consistent with known yeast aging biology. Confidence of 0.65 is appropriately calibrated given the indirect nature of the evidence. The mechanism class of \"deregulated_nutrient_sensing\" is reasonable.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}