gcy-18
C. elegans
Receptor-type guanylate cyclase gcy-18
What the model saw
Gene: gcy-18 Organism: Caenorhabditis elegans Known functions: Receptor-type guanylate cyclase gcy-18. ATP binding. guanylate cyclase activity. peptide receptor activity. phosphorus-oxygen lyase activity. protein kinase activity.
View unredacted entry
Receptor-type guanylate cyclase gcy-18. ATP binding. guanylate cyclase activity. peptide receptor activity. phosphorus-oxygen lyase activity. protein kinase activity.
Solver output
GCY-18 is a receptor-type guanylate cyclase that catalyzes the conversion of GTP to cGMP, a second messenger that modulates downstream signaling cascades including cGMP-dependent protein kinases (PKGs such as EGL-4 in C. elegans). cGMP/PKG signaling in C. elegans intersects with chemosensory neuron function and has been linked to lifespan regulation via modulation of insulin/IGF-1-like signaling (IIS) and thermosensory pathways. However, gcy-18 is one of many receptor guanylate cyclases in C. elegans with partially redundant and context-dependent roles; its specific ligand and neuronal expression pattern determine whether it promotes or opposes longevity. The co-annotation of protein kinase activity and peptide receptor activity suggests it may act as a bifunctional receptor kinase, but the net effect on lifespan-relevant pathways (IIS, DAF-16/FOXO) is not clearly established for this particular paralog. Given the ambiguity in which downstream effectors dominate and the lack of a clear pro- or anti-longevity assignment for gcy-18 specifically, the prediction remains unclear.
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 "unclear" while the ground truth is "anti_longevity." The model's reasoning about cGMP/PKG signaling and its intersection with IIS and chemosensory pathways is plausible but generic - it applies to many receptor guanylate cyclases in C. elegans. The model correctly identified the relevant pathway class but failed to commit to a direction. The model's uncertainty was somewhat reasonable given the large family of GCY proteins, but it ultimately got the answer wrong. The confidence was appropriately low (0.38), reflecting genuine uncertainty, but the prediction still missed the anti-longevity classification. The mechanistic reasoning, while not incorrect per se, was too generic and non-committal to be considered correct.
Raw API responses
solver
{
"reasoning": "GCY-18 is a receptor-type guanylate cyclase that catalyzes the conversion of GTP to cGMP, a second messenger that modulates downstream signaling cascades including cGMP-dependent protein kinases (PKGs such as EGL-4 in C. elegans). cGMP/PKG signaling in C. elegans intersects with chemosensory neuron function and has been linked to lifespan regulation via modulation of insulin/IGF-1-like signaling (IIS) and thermosensory pathways. However, gcy-18 is one of many receptor guanylate cyclases in C. elegans with partially redundant and context-dependent roles; its specific ligand and neuronal expression pattern determine whether it promotes or opposes longevity. The co-annotation of protein kinase activity and peptide receptor activity suggests it may act as a bifunctional receptor kinase, but the net effect on lifespan-relevant pathways (IIS, DAF-16/FOXO) is not clearly established for this particular paralog. Given the ambiguity in which downstream effectors dominate and the lack of a clear pro- or anti-longevity assignment for gcy-18 specifically, the prediction remains unclear.",
"confidence": 0.38,
"key_pathways": [
"cGMP signaling / guanylate cyclase-PKG axis",
"insulin/IGF-1-like signaling (IIS) / DAF-16 modulation via chemosensory neurons",
"peptide ligand-receptor signaling in sensory neurons"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" while the ground truth is \"anti_longevity.\" The model's reasoning about cGMP/PKG signaling and its intersection with IIS and chemosensory pathways is plausible but generic - it applies to many receptor guanylate cyclases in C. elegans. The model correctly identified the relevant pathway class but failed to commit to a direction. The model's uncertainty was somewhat reasonable given the large family of GCY proteins, but it ultimately got the answer wrong. The confidence was appropriately low (0.38), reflecting genuine uncertainty, but the prediction still missed the anti-longevity classification. The mechanistic reasoning, while not incorrect per se, was too generic and non-committal to be considered correct.",
"failure_mode": "appropriately_uncertain",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}