gpa-11
C. elegans
Guanine nucleotide-binding protein alpha-11 subunit
What the model saw
Gene: gpa-11 Organism: Caenorhabditis elegans Known functions: Guanine nucleotide-binding protein alpha-11 subunit. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTPase activity. guanyl nucleotide binding.
View unredacted entry
Guanine nucleotide-binding protein alpha-11 subunit. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTPase activity. guanyl nucleotide binding.
Solver output
gpa-11 encodes a Gα subunit that couples GPCRs to downstream effectors via GTPase activity and guanyl nucleotide binding. In C. elegans, Gα subunits can modulate longevity through multiple competing pathways: some Gα proteins (e.g., gpa-2, gpa-3) feed into the cAMP/PKA axis or the insulin/IGF-1-like signaling pathway (IIS), which is a major nutrient-sensing longevity regulator, while others act through chemosensory neurons to influence daf-16/FOXO activity. However, gpa-11 specifically has not been well-characterized in the context of longevity, and the directionality of its downstream signaling (pro- vs. anti-longevity effectors) cannot be confidently inferred from the available molecular function annotations alone. The GTPase activity and GPCR coupling are consistent with nutrient/chemosensory signal transduction, but without knowing which specific GPCR(s) and downstream effectors gpa-11 couples to, the net effect on lifespan remains ambiguous.
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 "pro_longevity." The model's uncertainty is understandable given limited annotation, but it still got the answer wrong. The mechanistic reasoning is generic and non-specific to gpa-11 — the model correctly identifies relevant pathways (IIS, chemosensory signaling) but explicitly acknowledges it cannot determine directionality. The model's low confidence (0.38) reflects appropriate epistemic humility, but the prediction is still incorrect. No specific mechanistic insight about gpa-11's pro-longevity role was provided.
Raw API responses
solver
{
"reasoning": "gpa-11 encodes a Gα subunit that couples GPCRs to downstream effectors via GTPase activity and guanyl nucleotide binding. In C. elegans, Gα subunits can modulate longevity through multiple competing pathways: some Gα proteins (e.g., gpa-2, gpa-3) feed into the cAMP/PKA axis or the insulin/IGF-1-like signaling pathway (IIS), which is a major nutrient-sensing longevity regulator, while others act through chemosensory neurons to influence daf-16/FOXO activity. However, gpa-11 specifically has not been well-characterized in the context of longevity, and the directionality of its downstream signaling (pro- vs. anti-longevity effectors) cannot be confidently inferred from the available molecular function annotations alone. The GTPase activity and GPCR coupling are consistent with nutrient/chemosensory signal transduction, but without knowing which specific GPCR(s) and downstream effectors gpa-11 couples to, the net effect on lifespan remains ambiguous.",
"confidence": 0.38,
"key_pathways": [
"GPCR signaling / cAMP-PKA axis",
"Insulin/IGF-1-like signaling (IIS) / daf-16 FOXO",
"Chemosensory neuron-mediated longevity signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" while the ground truth is \"pro_longevity.\" The model's uncertainty is understandable given limited annotation, but it still got the answer wrong. The mechanistic reasoning is generic and non-specific to gpa-11 — the model correctly identifies relevant pathways (IIS, chemosensory signaling) but explicitly acknowledges it cannot determine directionality. The model's low confidence (0.38) reflects appropriate epistemic humility, but the prediction is still incorrect. No specific mechanistic insight about gpa-11's pro-longevity role was provided.",
"failure_mode": "appropriately_uncertain",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}