gcy-28
C. elegans
Receptor-type guanylate cyclase gcy-28
What the model saw
Gene: gcy-28 Organism: Caenorhabditis elegans Known functions: Receptor-type guanylate cyclase gcy-28. ATP binding. guanylate cyclase activity. peptide receptor activity. phosphorus-oxygen lyase activity. protein kinase activity.
View unredacted entry
Receptor-type guanylate cyclase gcy-28. ATP binding. guanylate cyclase activity. peptide receptor activity. phosphorus-oxygen lyase activity. protein kinase activity.
Solver output
GCY-28 is a receptor-type guanylate cyclase that synthesizes cGMP upon peptide ligand binding, directly coupling extracellular peptide signals to intracellular second-messenger production. In C. elegans, cGMP signaling through receptor guanylate cyclases (e.g., DAF-11, GCY family) is a key upstream regulator of the insulin/IGF-1-like signaling (IIS) pathway and thermosensory/chemosensory neurons that modulate DAF-16/FOXO nuclear localization and longevity. Elevated cGMP from receptor GCs can activate cGMP-dependent protein kinases (PKGs such as EGL-4), which suppress IIS and promote DAF-16 activity, extending lifespan. The peptide receptor activity of GCY-28 places it as a sensory transducer in neuroendocrine circuits that integrate environmental cues with metabolic and longevity regulation. Its intrinsic protein kinase domain further suggests autophosphorylation-based signal modulation typical of receptor GCs that fine-tune cGMP output and downstream longevity 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 predicted pro_longevity but the ground truth is anti_longevity. The model constructed a plausible-sounding but ultimately incorrect mechanistic narrative, reasoning that GCY-28's cGMP production would suppress IIS and promote DAF-16 activity to extend lifespan. In reality, gcy-28 is anti-longevity, meaning its loss (not its activity) extends lifespan. The model's reasoning about cGMP signaling and receptor guanylate cyclases in C. elegans is generically reasonable but was applied in the wrong direction for this specific gene. The confidence of 0.62 is moderate but still wrong. The mechanism class of 'deregulated_nutrient_sensing' is also questionable for a peptide receptor guanylate cyclase.
Raw API responses
solver
{
"reasoning": "GCY-28 is a receptor-type guanylate cyclase that synthesizes cGMP upon peptide ligand binding, directly coupling extracellular peptide signals to intracellular second-messenger production. In C. elegans, cGMP signaling through receptor guanylate cyclases (e.g., DAF-11, GCY family) is a key upstream regulator of the insulin/IGF-1-like signaling (IIS) pathway and thermosensory/chemosensory neurons that modulate DAF-16/FOXO nuclear localization and longevity. Elevated cGMP from receptor GCs can activate cGMP-dependent protein kinases (PKGs such as EGL-4), which suppress IIS and promote DAF-16 activity, extending lifespan. The peptide receptor activity of GCY-28 places it as a sensory transducer in neuroendocrine circuits that integrate environmental cues with metabolic and longevity regulation. Its intrinsic protein kinase domain further suggests autophosphorylation-based signal modulation typical of receptor GCs that fine-tune cGMP output and downstream longevity pathways.",
"confidence": 0.62,
"key_pathways": [
"cGMP second-messenger signaling",
"insulin/IGF-1-like signaling (IIS) / DAF-16 regulation",
"neuroendocrine peptide receptor 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 constructed a plausible-sounding but ultimately incorrect mechanistic narrative, reasoning that GCY-28's cGMP production would suppress IIS and promote DAF-16 activity to extend lifespan. In reality, gcy-28 is anti-longevity, meaning its loss (not its activity) extends lifespan. The model's reasoning about cGMP signaling and receptor guanylate cyclases in C. elegans is generically reasonable but was applied in the wrong direction for this specific gene. The confidence of 0.62 is moderate but still wrong. The mechanism class of 'deregulated_nutrient_sensing' is also questionable for a peptide receptor guanylate cyclase.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}