goa-1
C. elegans
Guanine nucleotide-binding protein G(o) subunit alpha
What the model saw
Gene: goa-1 Organism: Caenorhabditis elegans Known functions: Guanine nucleotide-binding protein G(o) subunit alpha. G protein activity. G protein-coupled acetylcholine receptor activity. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTP binding. GTPase activity. guanyl nucleotide binding. protein binding. protein kinase binding. protein-membrane adaptor activity.
View unredacted entry
Guanine nucleotide-binding protein G(o) subunit alpha. G protein activity. G protein-coupled acetylcholine receptor activity. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTP binding. GTPase activity. guanyl nucleotide binding. protein binding. protein kinase binding. protein-membrane adaptor activity.
Solver output
GOA-1 is the C. elegans Gαo subunit that couples inhibitory G protein-coupled receptors (including acetylcholine receptors) to downstream effectors. In C. elegans, GOA-1 acts as a major negative regulator of locomotion and feeding behavior by inhibiting the EGL-30 (Gαq) pathway, which reduces pharyngeal pumping and food intake. Reduced GOA-1 signaling (loss-of-function) leads to hyperactive feeding and enhanced insulin/IGF-1-like signaling, while overactivation of GOA-1 suppresses feeding. Critically, GOA-1 activity antagonizes the DAF-2/insulin-IGF-1 pathway indirectly through modulation of neurotransmitter release and nutrient-sensing circuits; reduced GOA-1 function has been associated with increased lifespan in some contexts by dampening pro-aging signaling. However, GOA-1's primary role as an inhibitor of feeding and locomotion means its normal (wild-type) activity suppresses the hyperactive signaling states that can shorten lifespan, yet it also suppresses DAF-16/FOXO-activating pathways. The net effect of normal GOA-1 function is to dampen neuronal activity and feeding, which in the context of nutrient-sensing hallmarks of aging places it as a modulator that, when overactive, reduces food intake signaling and may limit pro-longevity signals through the insulin/IGF-1 axis.
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 confused and contradictory - it correctly identifies GOA-1 as a Gαo subunit that inhibits feeding/locomotion, but then incorrectly concludes it is anti-longevity. In C. elegans, GOA-1 (Gαo) is actually pro-longevity because it inhibits EGL-30 (Gαq) signaling, which reduces insulin/IGF-1-like signaling and promotes DAF-16/FOXO nuclear localization, thereby extending lifespan. Loss of goa-1 leads to hyperactive EGL-30 signaling, increased insulin-like peptide release, and shortened lifespan. The model even mentions some of these facts but then reaches the wrong conclusion. The reasoning is internally inconsistent and ultimately wrong on both the answer and the mechanism.
Raw API responses
solver
{
"reasoning": "GOA-1 is the C. elegans Gαo subunit that couples inhibitory G protein-coupled receptors (including acetylcholine receptors) to downstream effectors. In C. elegans, GOA-1 acts as a major negative regulator of locomotion and feeding behavior by inhibiting the EGL-30 (Gαq) pathway, which reduces pharyngeal pumping and food intake. Reduced GOA-1 signaling (loss-of-function) leads to hyperactive feeding and enhanced insulin/IGF-1-like signaling, while overactivation of GOA-1 suppresses feeding. Critically, GOA-1 activity antagonizes the DAF-2/insulin-IGF-1 pathway indirectly through modulation of neurotransmitter release and nutrient-sensing circuits; reduced GOA-1 function has been associated with increased lifespan in some contexts by dampening pro-aging signaling. However, GOA-1's primary role as an inhibitor of feeding and locomotion means its normal (wild-type) activity suppresses the hyperactive signaling states that can shorten lifespan, yet it also suppresses DAF-16/FOXO-activating pathways. The net effect of normal GOA-1 function is to dampen neuronal activity and feeding, which in the context of nutrient-sensing hallmarks of aging places it as a modulator that, when overactive, reduces food intake signaling and may limit pro-longevity signals through the insulin/IGF-1 axis.",
"confidence": 0.65,
"key_pathways": [
"Gαo/GOA-1 inhibitory GPCR signaling",
"EGL-30 (Gαq) / DAF-2 insulin-IGF-1 nutrient sensing axis",
"Cholinergic neurotransmission and pharyngeal pumping regulation"
],
"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 confused and contradictory - it correctly identifies GOA-1 as a Gαo subunit that inhibits feeding/locomotion, but then incorrectly concludes it is anti-longevity. In C. elegans, GOA-1 (Gαo) is actually pro-longevity because it inhibits EGL-30 (Gαq) signaling, which reduces insulin/IGF-1-like signaling and promotes DAF-16/FOXO nuclear localization, thereby extending lifespan. Loss of goa-1 leads to hyperactive EGL-30 signaling, increased insulin-like peptide release, and shortened lifespan. The model even mentions some of these facts but then reaches the wrong conclusion. The reasoning is internally inconsistent and ultimately wrong on both the answer and the mechanism.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}