NPT1
S. cerevisiae
nicotinate phosphoribosyltransferase
What the model saw
Gene: NPT1 Organism: Saccharomyces cerevisiae Known functions: nicotinate phosphoribosyltransferase. nicotinate phosphoribosyltransferase activity. protein binding.
View unredacted entry
nicotinate phosphoribosyltransferase. nicotinate phosphoribosyltransferase activity. protein binding.
Solver output
NPT1 encodes nicotinate phosphoribosyltransferase, the rate-limiting enzyme in the Preiss-Handler NAD⁺ salvage pathway in S. cerevisiae. It catalyzes the conversion of nicotinic acid (niacin) to nicotinic acid mononucleotide (NaMN), a key step in regenerating the NAD⁺ pool. Elevated intracellular NAD⁺ levels directly activate Sir2 (yeast sirtuin), a NAD⁺-dependent histone deacetylase that suppresses rDNA recombination and extends replicative lifespan. Loss of NPT1 reduces NAD⁺ availability, diminishes Sir2 activity, and shortens replicative lifespan, while overexpression of NPT1 has been shown to extend lifespan in a Sir2-dependent manner. This places NPT1 squarely in the NAD⁺/sirtuin axis of nutrient sensing and 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 correctly predicted pro_longevity for NPT1 in S. cerevisiae. The mechanistic reasoning is excellent and accurate: NPT1 encodes nicotinate phosphoribosyltransferase in the Preiss-Handler NAD+ salvage pathway, and its role in maintaining NAD+ levels to activate Sir2 and extend replicative lifespan is well-established in the literature. The model correctly identifies that NPT1 loss reduces Sir2 activity and shortens lifespan, while overexpression extends it. The mechanism class of "deregulated_nutrient_sensing" is a reasonable categorization for the NAD+/sirtuin axis. High confidence (0.82) is appropriate given the well-characterized nature of this gene's role in yeast longevity.
Raw API responses
solver
{
"reasoning": "NPT1 encodes nicotinate phosphoribosyltransferase, the rate-limiting enzyme in the Preiss-Handler NAD⁺ salvage pathway in S. cerevisiae. It catalyzes the conversion of nicotinic acid (niacin) to nicotinic acid mononucleotide (NaMN), a key step in regenerating the NAD⁺ pool. Elevated intracellular NAD⁺ levels directly activate Sir2 (yeast sirtuin), a NAD⁺-dependent histone deacetylase that suppresses rDNA recombination and extends replicative lifespan. Loss of NPT1 reduces NAD⁺ availability, diminishes Sir2 activity, and shortens replicative lifespan, while overexpression of NPT1 has been shown to extend lifespan in a Sir2-dependent manner. This places NPT1 squarely in the NAD⁺/sirtuin axis of nutrient sensing and longevity regulation.",
"confidence": 0.82,
"key_pathways": [
"NAD+ salvage pathway (Preiss-Handler)",
"Sir2/sirtuin deacetylase activation",
"rDNA silencing and replicative lifespan regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for NPT1 in S. cerevisiae. The mechanistic reasoning is excellent and accurate: NPT1 encodes nicotinate phosphoribosyltransferase in the Preiss-Handler NAD+ salvage pathway, and its role in maintaining NAD+ levels to activate Sir2 and extend replicative lifespan is well-established in the literature. The model correctly identifies that NPT1 loss reduces Sir2 activity and shortens lifespan, while overexpression extends it. The mechanism class of \"deregulated_nutrient_sensing\" is a reasonable categorization for the NAD+/sirtuin axis. High confidence (0.82) is appropriate given the well-characterized nature of this gene's role in yeast longevity.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}