gpa-2
C. elegans
Guanine nucleotide-binding protein alpha-2 subunit
What the model saw
Gene: gpa-2 Organism: Caenorhabditis elegans Known functions: Guanine nucleotide-binding protein alpha-2 subunit. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTP binding. GTPase activity. guanyl nucleotide binding.
View unredacted entry
Guanine nucleotide-binding protein alpha-2 subunit. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTP binding. GTPase activity. guanyl nucleotide binding.
Solver output
GPA-2 is a Gα subunit that couples GPCRs to downstream effectors in C. elegans. Gα subunits in the context of nutrient/chemosensory signaling in C. elegans modulate the insulin/IGF-1-like signaling (IIS) pathway indirectly through neuroendocrine circuits; reduced sensory neuron signaling (e.g., via chemosensory GPCRs) is well-established to extend lifespan in C. elegans by dampening IIS and activating DAF-16/FOXO. GPA-2 specifically functions in amphid sensory neurons and has been shown to act in the same pathway as GPA-3 to regulate dauer formation and longevity, where loss of function promotes longevity by reducing pro-aging neuroendocrine signals. Its GTPase activity cycles the Gα between active and inactive states, and its normal (active) function promotes signaling that suppresses DAF-16, thus the normal function of gpa-2 is anti-longevity; however, published data in C. elegans indicate gpa-2 loss-of-function extends lifespan, meaning the normal function of the gene opposes longevity. Therefore, the wild-type gpa-2 function is anti-longevity by sustaining sensory neuron-driven IIS activation and suppression of DAF-16/FOXO.
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 "pro_longevity" but the ground truth is also "pro_longevity," so the final answer label matches. However, the model's reasoning is internally contradictory and ultimately concludes the opposite of what it labeled. The model's reasoning explicitly states: "the wild-type gpa-2 function is anti-longevity" and "gpa-2 loss-of-function extends lifespan, meaning the normal function of the gene opposes longevity." This reasoning would lead to an "anti_longevity" classification, yet the model labeled it "pro_longevity." The model appears to have confused itself — the reasoning supports anti_longevity while the label says pro_longevity. The ground truth is pro_longevity, meaning gpa-2 promotes longevity (its presence/activity extends lifespan), which contradicts the model's mechanistic reasoning about loss-of-function extending lifespan. The answer label happens to match the ground truth, but the reasoning is wrong and contradicts the label given. This is a case of right answer with wrong reasoning (or possibly a labeling error by the model).
Raw API responses
solver
{
"reasoning": "GPA-2 is a Gα subunit that couples GPCRs to downstream effectors in C. elegans. Gα subunits in the context of nutrient/chemosensory signaling in C. elegans modulate the insulin/IGF-1-like signaling (IIS) pathway indirectly through neuroendocrine circuits; reduced sensory neuron signaling (e.g., via chemosensory GPCRs) is well-established to extend lifespan in C. elegans by dampening IIS and activating DAF-16/FOXO. GPA-2 specifically functions in amphid sensory neurons and has been shown to act in the same pathway as GPA-3 to regulate dauer formation and longevity, where loss of function promotes longevity by reducing pro-aging neuroendocrine signals. Its GTPase activity cycles the Gα between active and inactive states, and its normal (active) function promotes signaling that suppresses DAF-16, thus the normal function of gpa-2 is anti-longevity; however, published data in C. elegans indicate gpa-2 loss-of-function extends lifespan, meaning the normal function of the gene opposes longevity. Therefore, the wild-type gpa-2 function is anti-longevity by sustaining sensory neuron-driven IIS activation and suppression of DAF-16/FOXO.",
"confidence": 0.62,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) / DAF-16 FOXO suppression",
"GPCR-coupled chemosensory neuroendocrine signaling",
"dauer formation and lifespan regulation via Gα signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is also \"pro_longevity,\" so the final answer label matches. However, the model's reasoning is internally contradictory and ultimately concludes the opposite of what it labeled. The model's reasoning explicitly states: \"the wild-type gpa-2 function is anti-longevity\" and \"gpa-2 loss-of-function extends lifespan, meaning the normal function of the gene opposes longevity.\" This reasoning would lead to an \"anti_longevity\" classification, yet the model labeled it \"pro_longevity.\" The model appears to have confused itself — the reasoning supports anti_longevity while the label says pro_longevity. The ground truth is pro_longevity, meaning gpa-2 promotes longevity (its presence/activity extends lifespan), which contradicts the model's mechanistic reasoning about loss-of-function extending lifespan. The answer label happens to match the ground truth, but the reasoning is wrong and contradicts the label given. This is a case of right answer with wrong reasoning (or possibly a labeling error by the model).",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}