ADE12
S. cerevisiae
adenylosuccinate synthase
What the model saw
Gene: ADE12 Organism: Saccharomyces cerevisiae Known functions: adenylosuccinate synthase. DNA replication origin binding. GTP binding. adenylosuccinate synthase activity. magnesium ion binding. nucleotide binding. protein binding.
View unredacted entry
adenylosuccinate synthase. DNA replication origin binding. GTP binding. adenylosuccinate synthase activity. magnesium ion binding. nucleotide binding. protein binding.
Solver output
ADE12 encodes adenylosuccinate synthase, which catalyzes the first committed step in the de novo synthesis of AMP from IMP, converting IMP + GTP + aspartate → adenylosuccinate. This reaction is central to purine nucleotide biosynthesis and directly regulates the cellular AMP/ATP ratio. Maintaining adequate AMP levels supports AMPK activation, a key energy-sensing kinase that promotes longevity by inhibiting mTORC1 and activating autophagy. Additionally, ADE12's DNA replication origin binding activity suggests a role in coordinating nucleotide availability with DNA replication fidelity, linking purine metabolism to genomic stability. Disruption of ADE12 leads to adenine auxotrophy and accumulation of toxic purine intermediates (e.g., SAICAR/AIR), which can cause oxidative stress and DNA damage. Thus, normal ADE12 function supports purine homeostasis, energy sensing, and genome integrity, all of which are pro-longevity.
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 pro_longevity but the ground truth is anti_longevity. The model's reasoning is plausible on the surface (ADE12 supports purine biosynthesis, which could be seen as beneficial), but it reaches the wrong conclusion. The model failed to consider that ADE12, as an anti-longevity gene, likely promotes growth/proliferation pathways that reduce lifespan when active. In yeast, genes involved in purine biosynthesis and nucleotide metabolism can be anti-longevity because they support anabolic/growth processes that antagonize longevity. The model's AMPK/mTOR reasoning is speculative and not well-grounded for yeast specifically (yeast AMPK homolog Snf1 regulation via AMP is not as directly analogous). The model showed moderate confidence (0.65) in the wrong direction.
Raw API responses
solver
{
"reasoning": "ADE12 encodes adenylosuccinate synthase, which catalyzes the first committed step in the de novo synthesis of AMP from IMP, converting IMP + GTP + aspartate → adenylosuccinate. This reaction is central to purine nucleotide biosynthesis and directly regulates the cellular AMP/ATP ratio. Maintaining adequate AMP levels supports AMPK activation, a key energy-sensing kinase that promotes longevity by inhibiting mTORC1 and activating autophagy. Additionally, ADE12's DNA replication origin binding activity suggests a role in coordinating nucleotide availability with DNA replication fidelity, linking purine metabolism to genomic stability. Disruption of ADE12 leads to adenine auxotrophy and accumulation of toxic purine intermediates (e.g., SAICAR/AIR), which can cause oxidative stress and DNA damage. Thus, normal ADE12 function supports purine homeostasis, energy sensing, and genome integrity, all of which are pro-longevity.",
"confidence": 0.65,
"key_pathways": [
"de novo purine biosynthesis / AMP synthesis",
"AMPK energy sensing via AMP/ATP ratio",
"DNA replication origin coordination"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is plausible on the surface (ADE12 supports purine biosynthesis, which could be seen as beneficial), but it reaches the wrong conclusion. The model failed to consider that ADE12, as an anti-longevity gene, likely promotes growth/proliferation pathways that reduce lifespan when active. In yeast, genes involved in purine biosynthesis and nucleotide metabolism can be anti-longevity because they support anabolic/growth processes that antagonize longevity. The model's AMPK/mTOR reasoning is speculative and not well-grounded for yeast specifically (yeast AMPK homolog Snf1 regulation via AMP is not as directly analogous). The model showed moderate confidence (0.65) in the wrong direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}