HPT1
S. cerevisiae
hypoxanthine phosphoribosyltransferase
What the model saw
Gene: HPT1 Organism: Saccharomyces cerevisiae Known functions: hypoxanthine phosphoribosyltransferase. guanine phosphoribosyltransferase activity. hypoxanthine phosphoribosyltransferase activity.
View unredacted entry
hypoxanthine phosphoribosyltransferase. guanine phosphoribosyltransferase activity. hypoxanthine phosphoribosyltransferase activity.
Solver output
HPT1 encodes a hypoxanthine-guanine phosphoribosyltransferase (HGPRT) in S. cerevisiae, which catalyzes the salvage of hypoxanthine and guanine into IMP and GMP, respectively, via the purine salvage pathway. Efficient purine salvage reduces the energetic cost of de novo purine biosynthesis and maintains intracellular purine nucleotide pools (ATP, GTP), which are critical for energy metabolism and biosynthetic reactions. Adequate purine nucleotide availability supports NAD+ metabolism and AMPK/TOR nutrient-sensing pathways that are central regulators of longevity. Disruption of purine salvage forces reliance on costly de novo synthesis and can perturb nucleotide balance, potentially impairing ribosome biogenesis and translation fidelity. Additionally, proper IMP/GMP balance feeds into NAD+ precursor metabolism, linking purine salvage to sirtuin-dependent longevity pathways in yeast.
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. HPT1 is actually anti-longevity in yeast, meaning its deletion extends lifespan. The model's reasoning is plausible-sounding but incorrect - it argues that HPT1 supports purine salvage and thus energy metabolism, making it pro-longevity. However, the actual biology is that HPT1 deletion extends lifespan, likely because HPT1 activity can be detrimental (e.g., through production of toxic nucleotide analogs or through effects on purine pools that activate TOR). The model constructed a coherent but ultimately wrong mechanistic narrative, and had moderate confidence (0.62) in the wrong direction.
Raw API responses
solver
{
"reasoning": "HPT1 encodes a hypoxanthine-guanine phosphoribosyltransferase (HGPRT) in S. cerevisiae, which catalyzes the salvage of hypoxanthine and guanine into IMP and GMP, respectively, via the purine salvage pathway. Efficient purine salvage reduces the energetic cost of de novo purine biosynthesis and maintains intracellular purine nucleotide pools (ATP, GTP), which are critical for energy metabolism and biosynthetic reactions. Adequate purine nucleotide availability supports NAD+ metabolism and AMPK/TOR nutrient-sensing pathways that are central regulators of longevity. Disruption of purine salvage forces reliance on costly de novo synthesis and can perturb nucleotide balance, potentially impairing ribosome biogenesis and translation fidelity. Additionally, proper IMP/GMP balance feeds into NAD+ precursor metabolism, linking purine salvage to sirtuin-dependent longevity pathways in yeast.",
"confidence": 0.62,
"key_pathways": [
"purine salvage pathway",
"NAD+/nucleotide metabolism",
"TOR nutrient-sensing pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. HPT1 is actually anti-longevity in yeast, meaning its deletion extends lifespan. The model's reasoning is plausible-sounding but incorrect - it argues that HPT1 supports purine salvage and thus energy metabolism, making it pro-longevity. However, the actual biology is that HPT1 deletion extends lifespan, likely because HPT1 activity can be detrimental (e.g., through production of toxic nucleotide analogs or through effects on purine pools that activate TOR). The model constructed a coherent but ultimately wrong mechanistic narrative, and had moderate confidence (0.62) in the wrong direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}