gpa-1
C. elegans
Guanine nucleotide-binding protein alpha-1 subunit
What the model saw
Gene: gpa-1 Organism: Caenorhabditis elegans Known functions: Guanine nucleotide-binding protein alpha-1 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-1 subunit. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTPase activity. guanyl nucleotide binding.
Solver output
GPA-1 is a Gα subunit that couples G protein-coupled receptors to downstream signaling cascades. In C. elegans, Gα proteins modulate nutrient-sensing and neuroendocrine pathways, including those that regulate the insulin/IGF-1-like signaling (IIS) axis and cAMP-dependent pathways. Active Gα signaling (GTP-bound state via its GTPase activity) typically promotes growth and metabolic activity by stimulating downstream effectors, which can suppress DAF-16/FOXO transcriptional activity and reduce stress resistance. Loss-of-function in inhibitory Gα subunits or gain-of-function in stimulatory ones generally shortens lifespan in C. elegans by antagonizing the longevity-promoting effects of reduced IIS or dietary restriction pathways. GPA-1's binding to Gβγ complexes and GPCRs positions it as an upstream activator of pro-growth, anti-longevity signaling, analogous to the role of Gαs/Gαi proteins in nutrient and chemosensory circuits that modulate lifespan.
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 anti_longevity for gpa-1. However, the mechanistic reasoning is speculative and not well-grounded in the specific literature on gpa-1. The model invokes a generic framework about Gα proteins modulating IIS/DAF-16 and cAMP/PKA pathways, but gpa-1 in C. elegans is actually known to function in chemosensory/olfactory signaling (specifically in AWA neurons) and its role in longevity is more directly tied to sensory neuron signaling affecting lifespan rather than the IIS axis or nutrient sensing per se. The reasoning is largely generic and hand-wavy, applying broad G-protein biology rather than gpa-1-specific mechanisms. The confidence (0.62) is reasonable given the uncertainty, but the mechanistic class of 'deregulated_nutrient_sensing' is not the most accurate description of gpa-1's known function in longevity regulation.
Raw API responses
solver
{
"reasoning": "GPA-1 is a Gα subunit that couples G protein-coupled receptors to downstream signaling cascades. In C. elegans, Gα proteins modulate nutrient-sensing and neuroendocrine pathways, including those that regulate the insulin/IGF-1-like signaling (IIS) axis and cAMP-dependent pathways. Active Gα signaling (GTP-bound state via its GTPase activity) typically promotes growth and metabolic activity by stimulating downstream effectors, which can suppress DAF-16/FOXO transcriptional activity and reduce stress resistance. Loss-of-function in inhibitory Gα subunits or gain-of-function in stimulatory ones generally shortens lifespan in C. elegans by antagonizing the longevity-promoting effects of reduced IIS or dietary restriction pathways. GPA-1's binding to Gβγ complexes and GPCRs positions it as an upstream activator of pro-growth, anti-longevity signaling, analogous to the role of Gαs/Gαi proteins in nutrient and chemosensory circuits that modulate lifespan.",
"confidence": 0.62,
"key_pathways": [
"Insulin/IGF-1-like signaling (IIS) / DAF-2–DAF-16 axis",
"G protein-coupled receptor (GPCR) neuroendocrine signaling",
"cAMP/PKA nutrient-sensing pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for gpa-1. However, the mechanistic reasoning is speculative and not well-grounded in the specific literature on gpa-1. The model invokes a generic framework about Gα proteins modulating IIS/DAF-16 and cAMP/PKA pathways, but gpa-1 in C. elegans is actually known to function in chemosensory/olfactory signaling (specifically in AWA neurons) and its role in longevity is more directly tied to sensory neuron signaling affecting lifespan rather than the IIS axis or nutrient sensing per se. The reasoning is largely generic and hand-wavy, applying broad G-protein biology rather than gpa-1-specific mechanisms. The confidence (0.62) is reasonable given the uncertainty, but the mechanistic class of 'deregulated_nutrient_sensing' is not the most accurate description of gpa-1's known function in longevity regulation.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}