che-3
C. elegans
Cytoplasmic dynein 2 heavy chain 1
What the model saw
Gene: che-3 Organism: Caenorhabditis elegans Known functions: Cytoplasmic dynein 2 heavy chain 1. ATP binding. dynein intermediate chain binding. dynein light intermediate chain binding. microtubule motor activity. minus-end-directed microtubule motor activity.
View unredacted entry
Cytoplasmic dynein 2 heavy chain 1. ATP binding. dynein intermediate chain binding. dynein light intermediate chain binding. microtubule motor activity. minus-end-directed microtubule motor activity.
Solver output
che-3 encodes the cytoplasmic dynein 2 heavy chain, which is the core motor subunit responsible for retrograde intraflagellar transport (IFT) in cilia. In C. elegans, functional cilia on sensory neurons (amphid and phasmid neurons) are required for the animal to sense environmental signals, including food/nutrient cues that activate insulin/IGF-1 signaling (IIS) through DAF-28 and other insulin-like peptides secreted from ciliated neurons. Loss of che-3 disrupts cilia structure and retrograde IFT, impairing sensory neuron function. This ciliary dysfunction reduces the activation of the DAF-2/insulin receptor pathway, thereby de-repressing the FOXO transcription factor DAF-16, which promotes stress resistance and longevity. Consistent with this, many cilia-defective mutants in C. elegans (including che-3) are long-lived, meaning the normal function of che-3 (maintaining cilia integrity and thus promoting IIS activation) acts to suppress DAF-16 and shorten 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 che-3. The mechanistic reasoning is excellent and accurate: che-3 encodes cytoplasmic dynein 2 heavy chain required for retrograde intraflagellar transport (IFT) in cilia; loss of che-3 disrupts cilia structure in sensory neurons, reducing insulin/IGF-1 signaling activation, thereby de-repressing DAF-16/FOXO and extending lifespan. This is well-established biology for cilia-defective mutants in C. elegans. The mechanism class "deregulated_nutrient_sensing" is a reasonable categorization, though "sensory neuron signaling" might be more precise. The key pathways identified are all correct and relevant. Confidence of 0.72 is appropriate given the complexity of the reasoning chain.
Raw API responses
solver
{
"reasoning": "che-3 encodes the cytoplasmic dynein 2 heavy chain, which is the core motor subunit responsible for retrograde intraflagellar transport (IFT) in cilia. In C. elegans, functional cilia on sensory neurons (amphid and phasmid neurons) are required for the animal to sense environmental signals, including food/nutrient cues that activate insulin/IGF-1 signaling (IIS) through DAF-28 and other insulin-like peptides secreted from ciliated neurons. Loss of che-3 disrupts cilia structure and retrograde IFT, impairing sensory neuron function. This ciliary dysfunction reduces the activation of the DAF-2/insulin receptor pathway, thereby de-repressing the FOXO transcription factor DAF-16, which promotes stress resistance and longevity. Consistent with this, many cilia-defective mutants in C. elegans (including che-3) are long-lived, meaning the normal function of che-3 (maintaining cilia integrity and thus promoting IIS activation) acts to suppress DAF-16 and shorten lifespan.",
"confidence": 0.72,
"key_pathways": [
"intraflagellar transport / cilia maintenance",
"insulin/IGF-1 signaling (DAF-2/DAF-16 axis)",
"sensory neuron-mediated neuroendocrine regulation of lifespan"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for che-3. The mechanistic reasoning is excellent and accurate: che-3 encodes cytoplasmic dynein 2 heavy chain required for retrograde intraflagellar transport (IFT) in cilia; loss of che-3 disrupts cilia structure in sensory neurons, reducing insulin/IGF-1 signaling activation, thereby de-repressing DAF-16/FOXO and extending lifespan. This is well-established biology for cilia-defective mutants in C. elegans. The mechanism class \"deregulated_nutrient_sensing\" is a reasonable categorization, though \"sensory neuron signaling\" might be more precise. The key pathways identified are all correct and relevant. Confidence of 0.72 is appropriate given the complexity of the reasoning chain.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}