dnc
D. melanogaster
dunce
What the model saw
Gene: dnc Organism: Drosophila melanogaster Known functions: dunce. 3',5'-cyclic-AMP phosphodiesterase activity. 3',5'-cyclic-GMP phosphodiesterase activity. 3',5'-cyclic-nucleotide phosphodiesterase activity. phosphoric diester hydrolase activity.
View unredacted entry
dunce. 3',5'-cyclic-AMP phosphodiesterase activity. 3',5'-cyclic-GMP phosphodiesterase activity. 3',5'-cyclic-nucleotide phosphodiesterase activity. phosphoric diester hydrolase activity.
Solver output
The dunce (dnc) gene encodes a cAMP-specific phosphodiesterase (PDE) that hydrolyzes 3',5'-cyclic AMP (and cGMP) into their inactive 5'-monophosphate forms. By degrading cAMP, dnc opposes cAMP-PKA signaling, which is a key branch of nutrient/energy sensing pathways. Elevated cAMP-PKA activity is generally associated with enhanced stress resistance and longevity in multiple model organisms, including Drosophila, where reduced PKA activity or increased cAMP can extend lifespan. Loss-of-function of dnc in flies leads to elevated cAMP levels and altered learning/memory, but the normal function of dnc (i.e., degrading cAMP) would dampen pro-longevity cAMP signaling. Thus, the wild-type activity of dnc acts to suppress cAMP-PKA signaling, which is broadly pro-longevity, making dnc's normal function anti-longevity in effect. Additionally, cAMP signaling intersects with CREB-mediated transcription and mitochondrial biogenesis, further linking PDE activity to aging-relevant pathways.
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 dnc (dunce) in Drosophila. The mechanistic reasoning is sound: dnc encodes a cAMP phosphodiesterase that degrades cAMP, thereby suppressing cAMP-PKA signaling which is generally pro-longevity. The model correctly reasons that the wild-type function of dnc (degrading cAMP) is anti-longevity because it dampens pro-longevity cAMP signaling. The confidence of 0.65 is appropriately moderate. The mechanism class "deregulated_nutrient_sensing" is a reasonable categorization, though cAMP-PKA signaling in the context of learning/memory and aging in Drosophila could also be framed differently. Overall, the reasoning is logically coherent and well-supported.
Raw API responses
solver
{
"reasoning": "The dunce (dnc) gene encodes a cAMP-specific phosphodiesterase (PDE) that hydrolyzes 3',5'-cyclic AMP (and cGMP) into their inactive 5'-monophosphate forms. By degrading cAMP, dnc opposes cAMP-PKA signaling, which is a key branch of nutrient/energy sensing pathways. Elevated cAMP-PKA activity is generally associated with enhanced stress resistance and longevity in multiple model organisms, including Drosophila, where reduced PKA activity or increased cAMP can extend lifespan. Loss-of-function of dnc in flies leads to elevated cAMP levels and altered learning/memory, but the normal function of dnc (i.e., degrading cAMP) would dampen pro-longevity cAMP signaling. Thus, the wild-type activity of dnc acts to suppress cAMP-PKA signaling, which is broadly pro-longevity, making dnc's normal function anti-longevity in effect. Additionally, cAMP signaling intersects with CREB-mediated transcription and mitochondrial biogenesis, further linking PDE activity to aging-relevant pathways.",
"confidence": 0.65,
"key_pathways": [
"cAMP-PKA signaling",
"cyclic nucleotide hydrolysis",
"CREB transcriptional regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for dnc (dunce) in Drosophila. The mechanistic reasoning is sound: dnc encodes a cAMP phosphodiesterase that degrades cAMP, thereby suppressing cAMP-PKA signaling which is generally pro-longevity. The model correctly reasons that the wild-type function of dnc (degrading cAMP) is anti-longevity because it dampens pro-longevity cAMP signaling. The confidence of 0.65 is appropriately moderate. The mechanism class \"deregulated_nutrient_sensing\" is a reasonable categorization, though cAMP-PKA signaling in the context of learning/memory and aging in Drosophila could also be framed differently. Overall, the reasoning is logically coherent and well-supported.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}