nac-3
C. elegans
Sodium-dependent high-affinity dicarboxylate transporter 3
What the model saw
Gene: nac-3 Organism: Caenorhabditis elegans Known functions: Sodium-dependent high-affinity dicarboxylate transporter 3. citrate transmembrane transporter activity. high-affinity sodium:dicarboxylate symporter activity. succinate transmembrane transporter activity. transmembrane transporter activity.
View unredacted entry
Sodium-dependent high-affinity dicarboxylate transporter 3. citrate transmembrane transporter activity. high-affinity sodium:dicarboxylate symporter activity. succinate transmembrane transporter activity. transmembrane transporter activity.
Solver output
nac-3 encodes a sodium-dependent high-affinity dicarboxylate transporter responsible for importing TCA cycle intermediates—specifically citrate and succinate—into cells via a Na⁺-coupled symport mechanism. Elevated import of citrate and succinate fuels mitochondrial TCA cycle flux and promotes anabolic metabolism, which is associated with pro-growth, pro-aging signaling. Succinate in particular can act as a signaling metabolite that activates HIF-1α and inflammatory pathways, while citrate export from mitochondria supports lipid biosynthesis and acetyl-CoA availability for epigenetic modifications. High activity of such nutrient-importing transporters is generally associated with nutrient-replete, growth-promoting states that oppose longevity, analogous to how reduced nutrient sensing (e.g., dietary restriction) extends lifespan in C. elegans. Loss of nac-3 function would be predicted to mimic a nutrient-restricted state, reducing TCA intermediate availability and potentially extending lifespan.
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 anti_longevity for nac-3. The mechanistic reasoning is plausible and internally consistent: nac-3 imports TCA cycle intermediates (citrate, succinate), and high transporter activity promotes anabolic/pro-growth states that oppose longevity. Loss of function would mimic nutrient restriction and extend lifespan. The reasoning about succinate signaling via HIF-1α and citrate supporting lipid biosynthesis adds reasonable mechanistic depth. Confidence of 0.65 is appropriately calibrated for a less well-known gene. The mechanism class "deregulated_nutrient_sensing" is a reasonable fit. Overall solid reasoning with correct answer.
Raw API responses
solver
{
"reasoning": "nac-3 encodes a sodium-dependent high-affinity dicarboxylate transporter responsible for importing TCA cycle intermediates—specifically citrate and succinate—into cells via a Na⁺-coupled symport mechanism. Elevated import of citrate and succinate fuels mitochondrial TCA cycle flux and promotes anabolic metabolism, which is associated with pro-growth, pro-aging signaling. Succinate in particular can act as a signaling metabolite that activates HIF-1α and inflammatory pathways, while citrate export from mitochondria supports lipid biosynthesis and acetyl-CoA availability for epigenetic modifications. High activity of such nutrient-importing transporters is generally associated with nutrient-replete, growth-promoting states that oppose longevity, analogous to how reduced nutrient sensing (e.g., dietary restriction) extends lifespan in C. elegans. Loss of nac-3 function would be predicted to mimic a nutrient-restricted state, reducing TCA intermediate availability and potentially extending lifespan.",
"confidence": 0.65,
"key_pathways": [
"TCA cycle intermediate transport (citrate/succinate uptake)",
"Nutrient sensing and metabolic flux regulation",
"HIF-1α / succinate signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for nac-3. The mechanistic reasoning is plausible and internally consistent: nac-3 imports TCA cycle intermediates (citrate, succinate), and high transporter activity promotes anabolic/pro-growth states that oppose longevity. Loss of function would mimic nutrient restriction and extend lifespan. The reasoning about succinate signaling via HIF-1α and citrate supporting lipid biosynthesis adds reasonable mechanistic depth. Confidence of 0.65 is appropriately calibrated for a less well-known gene. The mechanism class \"deregulated_nutrient_sensing\" is a reasonable fit. Overall solid reasoning with correct answer.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}