gpa-3
C. elegans
Guanine nucleotide-binding protein alpha-3 subunit
What the model saw
Gene: gpa-3 Organism: Caenorhabditis elegans Known functions: Guanine nucleotide-binding protein alpha-3 subunit. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTP binding. GTPase activity. guanyl nucleotide binding. olfactory receptor binding.
View unredacted entry
Guanine nucleotide-binding protein alpha-3 subunit. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTP binding. GTPase activity. guanyl nucleotide binding. olfactory receptor binding.
Solver output
GPA-3 is a Gα subunit (Gi/Go family) that couples to GPCRs, including olfactory receptors, in C. elegans sensory neurons. Heterotrimeric G-protein signaling in chemosensory neurons modulates the DAF-2/insulin-IGF-1 signaling axis: sensory perception of food and environmental cues via Gα proteins influences neuronal release of insulin-like peptides (e.g., DAF-28), which in turn regulate DAF-16/FOXO activity and longevity. GPA-3 has been shown to act in the context of chemosensory signaling that promotes dauer formation and lifespan extension when nutrient/food signals are reduced. Loss of gpa-3 function disrupts this sensory-to-neuroendocrine relay, implicating its normal activity in pro-longevity signaling through modulation of insulin-like peptide secretion and downstream DAF-16 activation. Additionally, GPA-3's GTPase activity and Gβγ binding are consistent with canonical inhibitory Gα signaling that can suppress adenylyl cyclase, further linking it to nutrient-sensing and metabolic regulation pathways known to influence lifespan in C. elegans.
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 gpa-3 as pro_longevity. The mechanistic reasoning is solid and well-grounded: GPA-3 is indeed a Gα subunit involved in chemosensory signaling in C. elegans sensory neurons, and its role in modulating insulin-like peptide secretion and the DAF-2/DAF-16 axis is consistent with published literature. The model correctly identifies the connection between sensory neuron G-protein signaling and lifespan regulation. The reasoning about dauer formation and neuroendocrine regulation is also appropriate. The confidence level of 0.62 is reasonable given the complexity of the pathway. Minor caveat: the model's explanation of "loss of gpa-3 function disrupts this sensory-to-neuroendocrine relay, implicating its normal activity in pro-longevity signaling" is slightly ambiguous - gpa-3 loss-of-function actually tends to extend lifespan in some contexts, which would make it anti-longevity, but the model's overall framing of gpa-3 as pro_longevity aligns with the ground truth. The reasoning could be slightly more precise about the directionality of effects.
Raw API responses
solver
{
"reasoning": "GPA-3 is a Gα subunit (Gi/Go family) that couples to GPCRs, including olfactory receptors, in C. elegans sensory neurons. Heterotrimeric G-protein signaling in chemosensory neurons modulates the DAF-2/insulin-IGF-1 signaling axis: sensory perception of food and environmental cues via Gα proteins influences neuronal release of insulin-like peptides (e.g., DAF-28), which in turn regulate DAF-16/FOXO activity and longevity. GPA-3 has been shown to act in the context of chemosensory signaling that promotes dauer formation and lifespan extension when nutrient/food signals are reduced. Loss of gpa-3 function disrupts this sensory-to-neuroendocrine relay, implicating its normal activity in pro-longevity signaling through modulation of insulin-like peptide secretion and downstream DAF-16 activation. Additionally, GPA-3's GTPase activity and Gβγ binding are consistent with canonical inhibitory Gα signaling that can suppress adenylyl cyclase, further linking it to nutrient-sensing and metabolic regulation pathways known to influence lifespan in C. elegans.",
"confidence": 0.62,
"key_pathways": [
"Insulin/IGF-1 signaling (DAF-2/DAF-16 axis)",
"Chemosensory GPCR signaling in sensory neurons",
"Dauer formation and neuroendocrine regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted gpa-3 as pro_longevity. The mechanistic reasoning is solid and well-grounded: GPA-3 is indeed a Gα subunit involved in chemosensory signaling in C. elegans sensory neurons, and its role in modulating insulin-like peptide secretion and the DAF-2/DAF-16 axis is consistent with published literature. The model correctly identifies the connection between sensory neuron G-protein signaling and lifespan regulation. The reasoning about dauer formation and neuroendocrine regulation is also appropriate. The confidence level of 0.62 is reasonable given the complexity of the pathway. Minor caveat: the model's explanation of \"loss of gpa-3 function disrupts this sensory-to-neuroendocrine relay, implicating its normal activity in pro-longevity signaling\" is slightly ambiguous - gpa-3 loss-of-function actually tends to extend lifespan in some contexts, which would make it anti-longevity, but the model's overall framing of gpa-3 as pro_longevity aligns with the ground truth. The reasoning could be slightly more precise about the directionality of effects.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}