Naam
D. melanogaster
Nicotinamide amidase
What the model saw
Gene: Naam Organism: Drosophila melanogaster Known functions: Nicotinamide amidase. nicotinamide amidase. calcium ion binding. nicotinamidase activity.
View unredacted entry
Nicotinamide amidase. nicotinamide amidase. calcium ion binding. nicotinamidase activity.
Solver output
Naam encodes nicotinamide amidase (nicotinamidase), the enzyme that converts nicotinamide to nicotinic acid, the first step in the Preiss-Handler NAD+ salvage pathway. By recycling nicotinamide into NAD+, Naam sustains intracellular NAD+ levels, which are critical cofactors for sirtuins (e.g., dSir2 in Drosophila) and PARP enzymes. Elevated NAD+ activates sirtuin deacylases that modulate insulin/IGF-1 signaling, mitochondrial biogenesis, and stress resistance, all of which are established pro-longevity axes. Overexpression of nicotinamidase orthologs (e.g., pnc-1 in C. elegans) extends lifespan, and the mechanism is conserved through NAD+-dependent sirtuin activation. The calcium ion binding annotation may support additional regulatory roles but does not conflict with the primary pro-longevity NAD+ biosynthetic 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 Naam in Drosophila melanogaster. The mechanistic reasoning is excellent: it correctly identifies Naam as a nicotinamidase that converts nicotinamide to nicotinic acid in the NAD+ salvage pathway, links elevated NAD+ to sirtuin activation (dSir2), and draws a valid parallel to the well-established pnc-1 ortholog in C. elegans. The key pathways identified are all relevant and accurate. Confidence of 0.78 is appropriate given the indirect inference from ortholog data.
Raw API responses
solver
{
"reasoning": "Naam encodes nicotinamide amidase (nicotinamidase), the enzyme that converts nicotinamide to nicotinic acid, the first step in the Preiss-Handler NAD+ salvage pathway. By recycling nicotinamide into NAD+, Naam sustains intracellular NAD+ levels, which are critical cofactors for sirtuins (e.g., dSir2 in Drosophila) and PARP enzymes. Elevated NAD+ activates sirtuin deacylases that modulate insulin/IGF-1 signaling, mitochondrial biogenesis, and stress resistance, all of which are established pro-longevity axes. Overexpression of nicotinamidase orthologs (e.g., pnc-1 in C. elegans) extends lifespan, and the mechanism is conserved through NAD+-dependent sirtuin activation. The calcium ion binding annotation may support additional regulatory roles but does not conflict with the primary pro-longevity NAD+ biosynthetic function.",
"confidence": 0.78,
"key_pathways": [
"NAD+ salvage biosynthesis (Preiss-Handler pathway)",
"Sirtuin/dSir2 activation via NAD+",
"Insulin/IGF-1 signaling modulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Naam in Drosophila melanogaster. The mechanistic reasoning is excellent: it correctly identifies Naam as a nicotinamidase that converts nicotinamide to nicotinic acid in the NAD+ salvage pathway, links elevated NAD+ to sirtuin activation (dSir2), and draws a valid parallel to the well-established pnc-1 ortholog in C. elegans. The key pathways identified are all relevant and accurate. Confidence of 0.78 is appropriate given the indirect inference from ortholog data.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}