gpa-6
C. elegans
Guanine nucleotide-binding protein alpha-6 subunit
What the model saw
Gene: gpa-6 Organism: Caenorhabditis elegans Known functions: Guanine nucleotide-binding protein alpha-6 subunit. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTPase activity. guanyl nucleotide binding. protein binding.
View unredacted entry
Guanine nucleotide-binding protein alpha-6 subunit. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTPase activity. guanyl nucleotide binding. protein binding.
Solver output
GPA-6 is a Gα subunit in C. elegans that couples GPCRs to downstream signaling cascades. In C. elegans, sensory neuron G-protein signaling (particularly through chemosensory GPCRs) modulates the DAF-2/insulin-IGF-1 pathway by regulating neuronal release of insulin-like peptides; reduced sensory signaling typically extends lifespan by dampening systemic insulin/IGF-1 signaling and promoting DAF-16/FOXO nuclear activity. GPA-6 is expressed in sensory neurons (e.g., ASI, AWA) and its GTPase activity transduces GPCR signals that can promote release of pro-aging insulin-like peptides. Loss-of-function in sensory Gα subunits in C. elegans generally extends lifespan, implying the normal (wild-type) function of gpa-6 is to promote insulin-like peptide secretion and thus oppose longevity; however, the specific peptide cargo (pro- vs. anti-aging) of GPA-6-coupled neurons is not fully resolved. Given the predominant paradigm that sensory neuron Gα activity promotes aging via insulin signaling, the wild-type function of gpa-6 is tentatively anti-longevity, but uncertainty remains due to possible coupling to daf-28-like vs. ins-7-like peptides.
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 "anti_longevity." Interestingly, the model's own reasoning actually concludes that gpa-6 is "anti-longevity" (stating "the wild-type function of gpa-6 is tentatively anti-longevity"), yet the final prediction field says "pro_longevity." This is a self-contradictory response where the reasoning points toward the correct answer but the final answer is wrong. The mechanistic reasoning about sensory neuron Gα signaling promoting insulin-like peptide secretion and thus opposing longevity is actually consistent with the ground truth (anti_longevity), but the model submitted the opposite label. This appears to be a failure in translating the reasoning into the correct classification. The model's confidence of 0.55 reflects some uncertainty, but the final answer is still wrong.
Raw API responses
solver
{
"reasoning": "GPA-6 is a Gα subunit in C. elegans that couples GPCRs to downstream signaling cascades. In C. elegans, sensory neuron G-protein signaling (particularly through chemosensory GPCRs) modulates the DAF-2/insulin-IGF-1 pathway by regulating neuronal release of insulin-like peptides; reduced sensory signaling typically extends lifespan by dampening systemic insulin/IGF-1 signaling and promoting DAF-16/FOXO nuclear activity. GPA-6 is expressed in sensory neurons (e.g., ASI, AWA) and its GTPase activity transduces GPCR signals that can promote release of pro-aging insulin-like peptides. Loss-of-function in sensory Gα subunits in C. elegans generally extends lifespan, implying the normal (wild-type) function of gpa-6 is to promote insulin-like peptide secretion and thus oppose longevity; however, the specific peptide cargo (pro- vs. anti-aging) of GPA-6-coupled neurons is not fully resolved. Given the predominant paradigm that sensory neuron Gα activity promotes aging via insulin signaling, the wild-type function of gpa-6 is tentatively anti-longevity, but uncertainty remains due to possible coupling to daf-28-like vs. ins-7-like peptides.",
"confidence": 0.55,
"key_pathways": [
"insulin/IGF-1 signaling (DAF-2/DAF-16 axis)",
"GPCR-coupled sensory neuron signaling",
"G-protein GTPase cycle"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" Interestingly, the model's own reasoning actually concludes that gpa-6 is \"anti-longevity\" (stating \"the wild-type function of gpa-6 is tentatively anti-longevity\"), yet the final prediction field says \"pro_longevity.\" This is a self-contradictory response where the reasoning points toward the correct answer but the final answer is wrong. The mechanistic reasoning about sensory neuron Gα signaling promoting insulin-like peptide secretion and thus opposing longevity is actually consistent with the ground truth (anti_longevity), but the model submitted the opposite label. This appears to be a failure in translating the reasoning into the correct classification. The model's confidence of 0.55 reflects some uncertainty, but the final answer is still wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}