AGC1
S. cerevisiae
citrin
What the model saw
Gene: AGC1 Organism: Saccharomyces cerevisiae Known functions: citrin. L-aspartate transmembrane transporter activity. L-glutamate transmembrane transporter activity. antiporter activity. uniporter activity.
View unredacted entry
citrin. L-aspartate transmembrane transporter activity. L-glutamate transmembrane transporter activity. antiporter activity. uniporter activity.
Solver output
AGC1 (also known as citrin in mammals) encodes the mitochondrial aspartate-glutamate carrier, a key component of the malate-aspartate shuttle. In S. cerevisiae, Agc1p mediates the antiport of aspartate and glutamate across the inner mitochondrial membrane, which is essential for transferring reducing equivalents (NADH) from the cytoplasm into the mitochondrial matrix for efficient oxidative phosphorylation. By sustaining mitochondrial respiratory capacity and NAD+/NADH redox balance, AGC1 supports healthy mitochondrial function and energy metabolism. Loss of this transporter impairs the malate-aspartate shuttle, leading to cytoplasmic NADH accumulation, reduced mitochondrial respiration, and metabolic stress — hallmarks associated with mitochondrial dysfunction and accelerated aging. Maintenance of mitochondrial membrane transport and redox homeostasis is broadly associated with extended lifespan 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 AGC1 as pro_longevity, but the ground truth is anti_longevity. The model's mechanistic reasoning is plausible in general terms (AGC1 as a mitochondrial aspartate-glutamate carrier involved in the malate-aspartate shuttle and redox homeostasis), but it incorrectly concludes that loss of AGC1 would accelerate aging, when in fact AGC1 appears to be anti-longevity (meaning its deletion or loss likely extends lifespan). The model's logic — that maintaining mitochondrial function supports longevity — is reasonable but leads to the wrong conclusion in this case. Anti-longevity genes in yeast are those whose deletion extends lifespan, suggesting AGC1 activity may actually limit lifespan, possibly through mechanisms like promoting mitochondrial respiration that generates ROS or other aging-related byproducts. The model had moderate confidence (0.62) but was still wrong on the direction of effect.
Raw API responses
solver
{
"reasoning": "AGC1 (also known as citrin in mammals) encodes the mitochondrial aspartate-glutamate carrier, a key component of the malate-aspartate shuttle. In S. cerevisiae, Agc1p mediates the antiport of aspartate and glutamate across the inner mitochondrial membrane, which is essential for transferring reducing equivalents (NADH) from the cytoplasm into the mitochondrial matrix for efficient oxidative phosphorylation. By sustaining mitochondrial respiratory capacity and NAD+/NADH redox balance, AGC1 supports healthy mitochondrial function and energy metabolism. Loss of this transporter impairs the malate-aspartate shuttle, leading to cytoplasmic NADH accumulation, reduced mitochondrial respiration, and metabolic stress — hallmarks associated with mitochondrial dysfunction and accelerated aging. Maintenance of mitochondrial membrane transport and redox homeostasis is broadly associated with extended lifespan in yeast.",
"confidence": 0.62,
"key_pathways": [
"malate-aspartate shuttle",
"mitochondrial inner membrane transport",
"NAD+/NADH redox homeostasis"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted AGC1 as pro_longevity, but the ground truth is anti_longevity. The model's mechanistic reasoning is plausible in general terms (AGC1 as a mitochondrial aspartate-glutamate carrier involved in the malate-aspartate shuttle and redox homeostasis), but it incorrectly concludes that loss of AGC1 would accelerate aging, when in fact AGC1 appears to be anti-longevity (meaning its deletion or loss likely extends lifespan). The model's logic — that maintaining mitochondrial function supports longevity — is reasonable but leads to the wrong conclusion in this case. Anti-longevity genes in yeast are those whose deletion extends lifespan, suggesting AGC1 activity may actually limit lifespan, possibly through mechanisms like promoting mitochondrial respiration that generates ROS or other aging-related byproducts. The model had moderate confidence (0.62) but was still wrong on the direction of effect.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}