BNA6
S. cerevisiae
nicotinate-nucleotide diphosphorylase (carboxylating)
What the model saw
Gene: BNA6 Organism: Saccharomyces cerevisiae Known functions: nicotinate-nucleotide diphosphorylase (carboxylating). nicotinate-nucleotide diphosphorylase (carboxylating) activity. pentosyltransferase activity.
View unredacted entry
nicotinate-nucleotide diphosphorylase (carboxylating). nicotinate-nucleotide diphosphorylase (carboxylating) activity. pentosyltransferase activity.
Solver output
BNA6 encodes nicotinate-nucleotide diphosphorylase (carboxylating), which catalyzes the penultimate step in the de novo NAD⁺ biosynthesis pathway (the kynurenine/tryptophan pathway) in yeast, converting quinolinate to nicotinate mononucleotide (NaMN). NAD⁺ is a critical coenzyme and signaling molecule whose intracellular levels directly regulate the activity of Sir2/sirtuins, the yeast NAD⁺-dependent deacetylases that are central mediators of caloric restriction-induced longevity. By contributing to NAD⁺ biosynthesis, BNA6 supports sirtuin activity, which in turn promotes chromatin silencing, genomic stability, and extended replicative lifespan. Loss of BNA6 would reduce NAD⁺ availability, impairing Sir2 function and shortening lifespan, consistent with a pro-longevity role for the gene's normal function.
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 BNA6. The mechanistic reasoning is excellent and well-grounded: BNA6 encodes nicotinate-nucleotide diphosphorylase (carboxylating), which catalyzes a key step in de novo NAD+ biosynthesis via the kynurenine/tryptophan pathway. The model correctly connects NAD+ levels to Sir2/sirtuin activity and caloric restriction-induced longevity in yeast. The reasoning that loss of BNA6 would reduce NAD+ availability, impairing Sir2 function and shortening lifespan, is biochemically sound. The mechanism class of "deregulated_nutrient_sensing" is a reasonable categorization, though "metabolic" might be slightly more precise. Overall, this is a high-quality prediction with correct answer and sound mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "BNA6 encodes nicotinate-nucleotide diphosphorylase (carboxylating), which catalyzes the penultimate step in the de novo NAD⁺ biosynthesis pathway (the kynurenine/tryptophan pathway) in yeast, converting quinolinate to nicotinate mononucleotide (NaMN). NAD⁺ is a critical coenzyme and signaling molecule whose intracellular levels directly regulate the activity of Sir2/sirtuins, the yeast NAD⁺-dependent deacetylases that are central mediators of caloric restriction-induced longevity. By contributing to NAD⁺ biosynthesis, BNA6 supports sirtuin activity, which in turn promotes chromatin silencing, genomic stability, and extended replicative lifespan. Loss of BNA6 would reduce NAD⁺ availability, impairing Sir2 function and shortening lifespan, consistent with a pro-longevity role for the gene's normal function.",
"confidence": 0.72,
"key_pathways": [
"de novo NAD+ biosynthesis (kynurenine pathway)",
"Sir2/sirtuin NAD+-dependent deacetylase signaling",
"caloric restriction longevity pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for BNA6. The mechanistic reasoning is excellent and well-grounded: BNA6 encodes nicotinate-nucleotide diphosphorylase (carboxylating), which catalyzes a key step in de novo NAD+ biosynthesis via the kynurenine/tryptophan pathway. The model correctly connects NAD+ levels to Sir2/sirtuin activity and caloric restriction-induced longevity in yeast. The reasoning that loss of BNA6 would reduce NAD+ availability, impairing Sir2 function and shortening lifespan, is biochemically sound. The mechanism class of \"deregulated_nutrient_sensing\" is a reasonable categorization, though \"metabolic\" might be slightly more precise. Overall, this is a high-quality prediction with correct answer and sound mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}