nhr-8
C. elegans
Nuclear hormone receptor family member nhr-8
What the model saw
Gene: nhr-8 Organism: Caenorhabditis elegans Known functions: Nuclear hormone receptor family member nhr-8. DNA-binding transcription factor activity. RNA polymerase II cis-regulatory region sequence-specific DNA binding. nuclear receptor activity. sequence-specific DNA binding. zinc ion binding.
View unredacted entry
Nuclear hormone receptor family member nhr-8. DNA-binding transcription factor activity. RNA polymerase II cis-regulatory region sequence-specific DNA binding. nuclear receptor activity. sequence-specific DNA binding. zinc ion binding.
Solver output
NHR-8 is a C. elegans nuclear hormone receptor orthologous to vertebrate liver X receptor (LXR) and vitamin D receptor family members, functioning as a ligand-activated transcription factor that binds DNA via zinc finger domains. Nuclear hormone receptors in C. elegans, particularly those in the NHR superfamily, are central regulators of lipid metabolism, cholesterol homeostasis, and xenobiotic detoxification — processes tightly linked to nutrient sensing and metabolic fitness. Loss of nhr-8 in C. elegans has been shown to impair cholesterol and lipid homeostasis, reduce stress resistance, and shorten lifespan, indicating that its normal transcriptional activity supports longevity. Its role in coordinating metabolic gene expression programs places it within the deregulated nutrient-sensing hallmark, as nuclear receptors integrate hormonal and dietary signals to maintain anabolic/catabolic balance. The zinc ion binding activity is consistent with its C4 zinc finger DNA-binding domain, which is the canonical structural feature enabling sequence-specific binding at hormone response elements in target gene promoters.
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 nhr-8 as pro_longevity. The mechanistic reasoning is well-grounded: nhr-8 is indeed a nuclear hormone receptor involved in cholesterol/lipid homeostasis and xenobiotic detoxification in C. elegans, and loss of nhr-8 has been shown to shorten lifespan. The mechanism class of "deregulated_nutrient_sensing" is reasonable given the role of nuclear hormone receptors in integrating metabolic and hormonal signals. The model correctly identified the zinc finger DNA-binding domain and the orthology to vertebrate LXR/VDR family members. Confidence of 0.62 is appropriately calibrated given the specificity of the gene.
Raw API responses
solver
{
"reasoning": "NHR-8 is a C. elegans nuclear hormone receptor orthologous to vertebrate liver X receptor (LXR) and vitamin D receptor family members, functioning as a ligand-activated transcription factor that binds DNA via zinc finger domains. Nuclear hormone receptors in C. elegans, particularly those in the NHR superfamily, are central regulators of lipid metabolism, cholesterol homeostasis, and xenobiotic detoxification — processes tightly linked to nutrient sensing and metabolic fitness. Loss of nhr-8 in C. elegans has been shown to impair cholesterol and lipid homeostasis, reduce stress resistance, and shorten lifespan, indicating that its normal transcriptional activity supports longevity. Its role in coordinating metabolic gene expression programs places it within the deregulated nutrient-sensing hallmark, as nuclear receptors integrate hormonal and dietary signals to maintain anabolic/catabolic balance. The zinc ion binding activity is consistent with its C4 zinc finger DNA-binding domain, which is the canonical structural feature enabling sequence-specific binding at hormone response elements in target gene promoters.",
"confidence": 0.62,
"key_pathways": [
"nuclear hormone receptor / lipid homeostasis signaling",
"cholesterol and sterol metabolism",
"xenobiotic detoxification transcriptional regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted nhr-8 as pro_longevity. The mechanistic reasoning is well-grounded: nhr-8 is indeed a nuclear hormone receptor involved in cholesterol/lipid homeostasis and xenobiotic detoxification in C. elegans, and loss of nhr-8 has been shown to shorten lifespan. The mechanism class of \"deregulated_nutrient_sensing\" is reasonable given the role of nuclear hormone receptors in integrating metabolic and hormonal signals. The model correctly identified the zinc finger DNA-binding domain and the orthology to vertebrate LXR/VDR family members. Confidence of 0.62 is appropriately calibrated given the specificity of the gene.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}