ctbp-1
C. elegans
C-terminal-binding protein 1
What the model saw
Gene: ctbp-1 Organism: Caenorhabditis elegans Known functions: C-terminal-binding protein 1. DNA-binding transcription factor binding. NAD binding. RNA polymerase II-specific DNA-binding transcription factor binding. oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. transcription coactivator activity. transcription coregulator binding. transcription corepressor activity.
View unredacted entry
C-terminal-binding protein 1. DNA-binding transcription factor binding. NAD binding. RNA polymerase II-specific DNA-binding transcription factor binding. oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. transcription coactivator activity. transcription coregulator binding. transcription corepressor activity.
Solver output
CTBP-1 is a NAD⁺-binding transcriptional corepressor whose activity is directly regulated by the NAD⁺/NADH ratio, linking cellular redox/metabolic state to gene expression. In C. elegans, ctbp-1 has been shown to act downstream of dietary restriction and the germline signaling pathway to extend lifespan, functioning as a corepressor that represses pro-aging transcriptional programs when NAD⁺ levels are high (nutrient-replete or DR conditions). Its oxidoreductase activity (acting on CH-OH donors with NAD/NADP as acceptor) is integral to sensing the metabolic state of the cell. By coupling NAD⁺ availability to transcriptional repression of targets that antagonize longevity, CTBP-1 acts as a metabolic sensor that promotes longevity under conditions of reduced nutrient signaling. This places it squarely within the deregulated nutrient-sensing hallmark, specifically at the interface of NAD⁺ metabolism and transcriptional regulation of 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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about CTBP-1 acting as a NAD+-sensing corepressor that promotes longevity under dietary restriction is incorrect. In C. elegans, ctbp-1 is actually anti-longevity, meaning its loss (not its activity) extends lifespan. The model constructed a plausible-sounding but incorrect mechanistic narrative about CTBP-1 repressing pro-aging transcriptional programs. In reality, CTBP-1 appears to repress pro-longevity genes, so its loss extends lifespan. The model had moderate confidence (0.62) but was wrong on both the direction of effect and the mechanistic interpretation.
Raw API responses
solver
{
"reasoning": "CTBP-1 is a NAD⁺-binding transcriptional corepressor whose activity is directly regulated by the NAD⁺/NADH ratio, linking cellular redox/metabolic state to gene expression. In C. elegans, ctbp-1 has been shown to act downstream of dietary restriction and the germline signaling pathway to extend lifespan, functioning as a corepressor that represses pro-aging transcriptional programs when NAD⁺ levels are high (nutrient-replete or DR conditions). Its oxidoreductase activity (acting on CH-OH donors with NAD/NADP as acceptor) is integral to sensing the metabolic state of the cell. By coupling NAD⁺ availability to transcriptional repression of targets that antagonize longevity, CTBP-1 acts as a metabolic sensor that promotes longevity under conditions of reduced nutrient signaling. This places it squarely within the deregulated nutrient-sensing hallmark, specifically at the interface of NAD⁺ metabolism and transcriptional regulation of lifespan.",
"confidence": 0.62,
"key_pathways": [
"NAD+/NADH redox sensing and transcriptional corepression",
"dietary restriction longevity pathway",
"germline-to-soma longevity signaling"
],
"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 about CTBP-1 acting as a NAD+-sensing corepressor that promotes longevity under dietary restriction is incorrect. In C. elegans, ctbp-1 is actually anti-longevity, meaning its loss (not its activity) extends lifespan. The model constructed a plausible-sounding but incorrect mechanistic narrative about CTBP-1 repressing pro-aging transcriptional programs. In reality, CTBP-1 appears to repress pro-longevity genes, so its loss extends lifespan. The model had moderate confidence (0.62) but was wrong on both the direction of effect and the mechanistic interpretation.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}