cnb-1
C. elegans
EF-hand domain-containing protein;Protein phosphatase 2B regulatory subunit cnb-1
What the model saw
Gene: cnb-1 Organism: Caenorhabditis elegans Known functions: EF-hand domain-containing protein;Protein phosphatase 2B regulatory subunit cnb-1. calcium ion binding. calcium-dependent protein serine/threonine phosphatase regulator activity. phosphatase binding.
View unredacted entry
EF-hand domain-containing protein;Protein phosphatase 2B regulatory subunit cnb-1. calcium ion binding. calcium-dependent protein serine/threonine phosphatase regulator activity. phosphatase binding.
Solver output
cnb-1 encodes the regulatory B subunit of calcineurin (protein phosphatase 2B), a calcium/calmodulin-dependent serine/threonine phosphatase. In C. elegans, calcineurin (TAX-6/CNB-1) dephosphorylates and activates the NFAT-like transcription factor, but critically it also intersects with the insulin/IGF-1 signaling pathway by modulating DAF-16/FOXO nuclear localization and activity. Calcineurin activity can promote nuclear entry of stress-response transcription factors, and loss of calcineurin signaling has been shown to reduce lifespan in C. elegans, suggesting the normal function of cnb-1 supports longevity pathways. The EF-hand calcium-binding domain of CNB-1 is essential for sensing calcium signals that activate the calcineurin holoenzyme, linking calcium-dependent signaling to downstream transcriptional programs involved in stress resistance and longevity. Additionally, calcineurin/NFAT signaling intersects with mitochondrial function and cellular stress responses, further supporting a pro-longevity role for the intact regulatory subunit.
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. cnb-1 encodes the regulatory B subunit of calcineurin (PP2B), and in C. elegans, calcineurin activity (TAX-6/CNB-1) has been shown to suppress DAF-16/FOXO nuclear localization, thereby reducing stress resistance and lifespan. Loss of calcineurin function (including cnb-1 loss) actually extends lifespan, making cnb-1 anti_longevity. The model incorrectly reasoned that calcineurin promotes DAF-16 nuclear entry and that loss of calcineurin reduces lifespan — this is the opposite of what is established in the literature. The model's mechanistic reasoning is inverted. The confidence of 0.62 is moderate but still clearly wrong.
Raw API responses
solver
{
"reasoning": "cnb-1 encodes the regulatory B subunit of calcineurin (protein phosphatase 2B), a calcium/calmodulin-dependent serine/threonine phosphatase. In C. elegans, calcineurin (TAX-6/CNB-1) dephosphorylates and activates the NFAT-like transcription factor, but critically it also intersects with the insulin/IGF-1 signaling pathway by modulating DAF-16/FOXO nuclear localization and activity. Calcineurin activity can promote nuclear entry of stress-response transcription factors, and loss of calcineurin signaling has been shown to reduce lifespan in C. elegans, suggesting the normal function of cnb-1 supports longevity pathways. The EF-hand calcium-binding domain of CNB-1 is essential for sensing calcium signals that activate the calcineurin holoenzyme, linking calcium-dependent signaling to downstream transcriptional programs involved in stress resistance and longevity. Additionally, calcineurin/NFAT signaling intersects with mitochondrial function and cellular stress responses, further supporting a pro-longevity role for the intact regulatory subunit.",
"confidence": 0.62,
"key_pathways": [
"Calcineurin (PP2B) signaling",
"DAF-16/FOXO transcription factor regulation",
"Calcium-dependent stress response"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. cnb-1 encodes the regulatory B subunit of calcineurin (PP2B), and in C. elegans, calcineurin activity (TAX-6/CNB-1) has been shown to suppress DAF-16/FOXO nuclear localization, thereby reducing stress resistance and lifespan. Loss of calcineurin function (including cnb-1 loss) actually extends lifespan, making cnb-1 anti_longevity. The model incorrectly reasoned that calcineurin promotes DAF-16 nuclear entry and that loss of calcineurin reduces lifespan — this is the opposite of what is established in the literature. The model's mechanistic reasoning is inverted. The confidence of 0.62 is moderate but still clearly wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}