daf-4
C. elegans
Cell surface receptor daf-4;Serine/threonine-protein kinase receptor;receptor protein serine/threonine kinase
What the model saw
Gene: daf-4 Organism: Caenorhabditis elegans Known functions: Cell surface receptor daf-4;Serine/threonine-protein kinase receptor;receptor protein serine/threonine kinase. ATP binding. BMP binding. protein binding. protein kinase activity. transforming growth factor beta receptor activity. transmembrane receptor protein serine/threonine kinase activity.
View unredacted entry
Cell surface receptor daf-4;Serine/threonine-protein kinase receptor;receptor protein serine/threonine kinase. ATP binding. BMP binding. protein binding. protein kinase activity. transforming growth factor beta receptor activity. transmembrane receptor protein serine/threonine kinase activity.
Solver output
DAF-4 is the type II BMP/TGF-β receptor serine/threonine kinase in C. elegans, functioning as the obligate co-receptor for the DAF-7 TGF-β ligand signaling pathway. DAF-4 partners with the type I receptor DAF-1 to transduce signals through SMAD proteins (DAF-8/DAF-14), which antagonize the transcription factor DAF-3/SMAD and its co-factor DAF-5. This TGF-β/DAF-7 branch regulates dauer formation, feeding behavior, and stress responses in parallel to the insulin/IGF-1 pathway. Active DAF-4 signaling suppresses dauer entry and promotes reproductive growth; however, the TGF-β pathway also modulates lifespan by influencing nutrient sensing and metabolic state. Loss of daf-4 promotes constitutive dauer-like physiology, which is associated with extended lifespan, suggesting that normal DAF-4 activity opposes longevity. Nonetheless, DAF-4 also participates in the DBL-1/BMP branch regulating body size and innate immunity, where its activity can be pro-longevity through immune homeostasis. On balance, the dominant role of DAF-4 in the DAF-7 pathway—where its activity suppresses dauer and stress resistance—places it as a net pro-longevity signal under normal conditions, though the dauer-promoting loss-of-function phenotype complicates this classification.
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 identifies DAF-4 as the type II BMP/TGF-β receptor and accurately describes the mechanistic pathways (DAF-7/TGF-β branch, DBL-1/BMP branch, dauer formation, SMAD signaling). The model even correctly notes that "loss of daf-4 promotes constitutive dauer-like physiology, which is associated with extended lifespan, suggesting that normal DAF-4 activity opposes longevity" — which is exactly the anti_longevity classification in the ground truth. However, the model then contradicts itself and concludes that DAF-4 is "pro_longevity" with 0.72 confidence, citing the immune homeostasis role as the dominant factor. The ground truth classifies daf-4 as anti_longevity, meaning its normal activity shortens lifespan (loss-of-function extends lifespan). The model's mechanistic reasoning was largely correct but it drew the wrong final conclusion despite having the right information available in its reasoning.
Raw API responses
solver
{
"reasoning": "DAF-4 is the type II BMP/TGF-β receptor serine/threonine kinase in C. elegans, functioning as the obligate co-receptor for the DAF-7 TGF-β ligand signaling pathway. DAF-4 partners with the type I receptor DAF-1 to transduce signals through SMAD proteins (DAF-8/DAF-14), which antagonize the transcription factor DAF-3/SMAD and its co-factor DAF-5. This TGF-β/DAF-7 branch regulates dauer formation, feeding behavior, and stress responses in parallel to the insulin/IGF-1 pathway. Active DAF-4 signaling suppresses dauer entry and promotes reproductive growth; however, the TGF-β pathway also modulates lifespan by influencing nutrient sensing and metabolic state. Loss of daf-4 promotes constitutive dauer-like physiology, which is associated with extended lifespan, suggesting that normal DAF-4 activity opposes longevity. Nonetheless, DAF-4 also participates in the DBL-1/BMP branch regulating body size and innate immunity, where its activity can be pro-longevity through immune homeostasis. On balance, the dominant role of DAF-4 in the DAF-7 pathway—where its activity suppresses dauer and stress resistance—places it as a net pro-longevity signal under normal conditions, though the dauer-promoting loss-of-function phenotype complicates this classification.",
"confidence": 0.72,
"key_pathways": [
"TGF-β/DAF-7 signaling (DAF-4/DAF-1 receptor complex → DAF-8/DAF-14 SMADs → DAF-3 repression)",
"BMP/DBL-1 signaling pathway (body size and innate immunity)",
"Dauer formation and stress resistance regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identifies DAF-4 as the type II BMP/TGF-β receptor and accurately describes the mechanistic pathways (DAF-7/TGF-β branch, DBL-1/BMP branch, dauer formation, SMAD signaling). The model even correctly notes that \"loss of daf-4 promotes constitutive dauer-like physiology, which is associated with extended lifespan, suggesting that normal DAF-4 activity opposes longevity\" — which is exactly the anti_longevity classification in the ground truth. However, the model then contradicts itself and concludes that DAF-4 is \"pro_longevity\" with 0.72 confidence, citing the immune homeostasis role as the dominant factor. The ground truth classifies daf-4 as anti_longevity, meaning its normal activity shortens lifespan (loss-of-function extends lifespan). The model's mechanistic reasoning was largely correct but it drew the wrong final conclusion despite having the right information available in its reasoning.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}