gsa-1
C. elegans
Guanine nucleotide-binding protein G(s) subunit alpha
What the model saw
Gene: gsa-1 Organism: Caenorhabditis elegans Known functions: Guanine nucleotide-binding protein G(s) subunit alpha. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTP binding. GTPase activity. guanyl nucleotide binding. metal ion binding.
View unredacted entry
Guanine nucleotide-binding protein G(s) subunit alpha. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTP binding. GTPase activity. guanyl nucleotide binding. metal ion binding.
Solver output
gsa-1 encodes the stimulatory G-protein alpha subunit (Gαs) in C. elegans, which upon GPCR activation exchanges GDP for GTP and stimulates adenylyl cyclase to produce cAMP. Elevated cAMP activates PKA (kin-1/kin-2 in C. elegans), which phosphorylates and inhibits the FOXO transcription factor DAF-16, a central pro-longevity effector downstream of the insulin/IGF-1 signaling pathway. Gain-of-function mutations in gsa-1 or its downstream effectors shorten lifespan, while loss-of-function extends it, placing Gαs in the same pro-aging axis as DAF-2/insulin receptor signaling. The GSA-1→adenylyl cyclase→cAMP→PKA axis thus suppresses DAF-16-dependent stress resistance and longevity programs. This places gsa-1 squarely in the deregulated nutrient/insulin sensing hallmark of aging.
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 anti_longevity but the ground truth is pro_longevity. The model's reasoning is internally consistent and mechanistically plausible (GSA-1 → cAMP → PKA → DAF-16 inhibition = pro-aging), but it gets the GenAge classification wrong. In C. elegans, gsa-1 is classified as pro_longevity, which is counterintuitive given the model's reasoning. The actual experimental evidence likely shows that gsa-1 activity promotes longevity (possibly through a different mechanism or context than the model assumed). The model was confident (0.75) in the wrong direction. The mechanistic reasoning about the cAMP-PKA-DAF-16 axis is a reasonable hypothesis but apparently does not match the actual experimental findings recorded in GenAge. The model correctly identified the relevant pathways but drew the wrong conclusion about the net effect on longevity.
Raw API responses
solver
{
"reasoning": "gsa-1 encodes the stimulatory G-protein alpha subunit (Gαs) in C. elegans, which upon GPCR activation exchanges GDP for GTP and stimulates adenylyl cyclase to produce cAMP. Elevated cAMP activates PKA (kin-1/kin-2 in C. elegans), which phosphorylates and inhibits the FOXO transcription factor DAF-16, a central pro-longevity effector downstream of the insulin/IGF-1 signaling pathway. Gain-of-function mutations in gsa-1 or its downstream effectors shorten lifespan, while loss-of-function extends it, placing Gαs in the same pro-aging axis as DAF-2/insulin receptor signaling. The GSA-1→adenylyl cyclase→cAMP→PKA axis thus suppresses DAF-16-dependent stress resistance and longevity programs. This places gsa-1 squarely in the deregulated nutrient/insulin sensing hallmark of aging.",
"confidence": 0.75,
"key_pathways": [
"cAMP-PKA signaling (GSA-1 → adenylyl cyclase → PKA → DAF-16 inhibition)",
"Insulin/IGF-1 signaling pathway (DAF-2/DAF-16 axis)",
"G-protein coupled receptor signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity but the ground truth is pro_longevity. The model's reasoning is internally consistent and mechanistically plausible (GSA-1 → cAMP → PKA → DAF-16 inhibition = pro-aging), but it gets the GenAge classification wrong. In C. elegans, gsa-1 is classified as pro_longevity, which is counterintuitive given the model's reasoning. The actual experimental evidence likely shows that gsa-1 activity promotes longevity (possibly through a different mechanism or context than the model assumed). The model was confident (0.75) in the wrong direction. The mechanistic reasoning about the cAMP-PKA-DAF-16 axis is a reasonable hypothesis but apparently does not match the actual experimental findings recorded in GenAge. The model correctly identified the relevant pathways but drew the wrong conclusion about the net effect on longevity.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": true
}