npr-1
C. elegans
Neuropeptide receptor npr-1
What the model saw
Gene: npr-1 Organism: Caenorhabditis elegans Known functions: Neuropeptide receptor npr-1. G protein-coupled receptor activity. neuropeptide Y receptor activity. neuropeptide receptor activity.
View unredacted entry
Neuropeptide receptor npr-1. G protein-coupled receptor activity. neuropeptide Y receptor activity. neuropeptide receptor activity.
Solver output
NPR-1 is a neuropeptide Y-like G protein-coupled receptor in C. elegans that mediates intercellular neuropeptide signaling. The high-activity allele of NPR-1 (215V) is well established to suppress aerotaxis and social feeding behaviors, reducing oxidative stress exposure and promoting aggregation-independent survival. NPR-1 signaling modulates neuroendocrine circuits that intersect with the DAF-2/insulin-IGF-1 pathway and oxygen-sensing neurons (URX), thereby influencing systemic stress responses and metabolic homeostasis. Loss of npr-1 function leads to hyperactive aerotaxis, increased ROS exposure, and shortened lifespan, while high-activity NPR-1 dampens these detrimental signals. This places NPR-1's normal (high-activity) function as pro-longevity through regulation of neuroendocrine intercellular communication that buffers oxidative and metabolic stress.
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. The model's reasoning is internally coherent but reaches the wrong conclusion. The model argues that high-activity NPR-1 (215V allele) promotes longevity by suppressing aerotaxis and oxidative stress, and that loss of npr-1 shortens lifespan. However, GenAge classifies npr-1 as anti_longevity, meaning the gene's normal function works against longevity (i.e., loss or reduction of npr-1 activity extends lifespan). The model conflates the effect of a specific gain-of-function allele (215V) with the gene's general longevity classification. In GenAge's framework, anti_longevity means that the gene normally limits lifespan — consistent with findings that npr-1 loss-of-function or certain allelic variants can extend lifespan. The model's mechanistic discussion of aerotaxis, URX neurons, and neuropeptide signaling is relevant but the directional conclusion is wrong. The confidence of 0.72 makes this a notably confident wrong answer.
Raw API responses
solver
{
"reasoning": "NPR-1 is a neuropeptide Y-like G protein-coupled receptor in C. elegans that mediates intercellular neuropeptide signaling. The high-activity allele of NPR-1 (215V) is well established to suppress aerotaxis and social feeding behaviors, reducing oxidative stress exposure and promoting aggregation-independent survival. NPR-1 signaling modulates neuroendocrine circuits that intersect with the DAF-2/insulin-IGF-1 pathway and oxygen-sensing neurons (URX), thereby influencing systemic stress responses and metabolic homeostasis. Loss of npr-1 function leads to hyperactive aerotaxis, increased ROS exposure, and shortened lifespan, while high-activity NPR-1 dampens these detrimental signals. This places NPR-1's normal (high-activity) function as pro-longevity through regulation of neuroendocrine intercellular communication that buffers oxidative and metabolic stress.",
"confidence": 0.72,
"key_pathways": [
"neuropeptide Y-like GPCR signaling",
"oxygen/aerotaxis neuroendocrine circuit (URX neurons)",
"insulin/IGF-1 (DAF-2) pathway crosstalk"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is internally coherent but reaches the wrong conclusion. The model argues that high-activity NPR-1 (215V allele) promotes longevity by suppressing aerotaxis and oxidative stress, and that loss of npr-1 shortens lifespan. However, GenAge classifies npr-1 as anti_longevity, meaning the gene's normal function works against longevity (i.e., loss or reduction of npr-1 activity extends lifespan). The model conflates the effect of a specific gain-of-function allele (215V) with the gene's general longevity classification. In GenAge's framework, anti_longevity means that the gene normally limits lifespan — consistent with findings that npr-1 loss-of-function or certain allelic variants can extend lifespan. The model's mechanistic discussion of aerotaxis, URX neurons, and neuropeptide signaling is relevant but the directional conclusion is wrong. The confidence of 0.72 makes this a notably confident wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": true
}