nhr-23
C. elegans
Nuclear hormone receptor family member nhr-23
What the model saw
Gene: nhr-23 Organism: Caenorhabditis elegans Known functions: Nuclear hormone receptor family member nhr-23. DNA-binding transcription factor activity. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II transcription 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-23. DNA-binding transcription factor activity. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II transcription regulatory region sequence-specific DNA binding. nuclear receptor activity. sequence-specific DNA binding. zinc ion binding.
Solver output
nhr-23 is the C. elegans ortholog of mammalian ROR (RAR-related orphan receptor) nuclear hormone receptors, which act as ligand-regulated transcription factors binding RNA Pol II cis-regulatory elements via zinc finger DNA-binding domains. Nuclear hormone receptors in C. elegans are key regulators of developmental timing, molting, and metabolic homeostasis; nhr-23 in particular controls molting cycles and epithelial integrity through transcriptional programs analogous to ROR-mediated gene regulation. ROR/NHR-23 activity modulates lipid metabolism and stress-response gene expression, pathways tightly linked to lifespan regulation in C. elegans. Reduced nhr-23 function disrupts molting and developmental progression, but its role as a transcriptional activator of homeostatic programs suggests its normal activity supports organismal fitness and longevity. The zinc ion binding and sequence-specific DNA binding activities place it as a direct transcriptional regulator of downstream longevity-relevant targets, most closely mapping to epigenetic/transcriptional reprogramming hallmarks of aging.
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 acknowledges that nhr-23 controls molting and that reduced function disrupts development, but then incorrectly concludes that its normal activity supports longevity. In reality, nhr-23 is anti-longevity, meaning its reduction or loss extends lifespan. The model's mechanistic reasoning is also questionable - it classifies the mechanism as "epigenetic_alterations" when nhr-23 is primarily a transcription factor involved in developmental timing/molting, not epigenetic reprogramming per se. The model had moderate confidence (0.62) but still got the direction wrong. The reasoning shows some awareness of nhr-23's role in molting but fails to connect this to the known finding that reducing nhr-23 activity extends lifespan in C. elegans.
Raw API responses
solver
{
"reasoning": "nhr-23 is the C. elegans ortholog of mammalian ROR (RAR-related orphan receptor) nuclear hormone receptors, which act as ligand-regulated transcription factors binding RNA Pol II cis-regulatory elements via zinc finger DNA-binding domains. Nuclear hormone receptors in C. elegans are key regulators of developmental timing, molting, and metabolic homeostasis; nhr-23 in particular controls molting cycles and epithelial integrity through transcriptional programs analogous to ROR-mediated gene regulation. ROR/NHR-23 activity modulates lipid metabolism and stress-response gene expression, pathways tightly linked to lifespan regulation in C. elegans. Reduced nhr-23 function disrupts molting and developmental progression, but its role as a transcriptional activator of homeostatic programs suggests its normal activity supports organismal fitness and longevity. The zinc ion binding and sequence-specific DNA binding activities place it as a direct transcriptional regulator of downstream longevity-relevant targets, most closely mapping to epigenetic/transcriptional reprogramming hallmarks of aging.",
"confidence": 0.62,
"key_pathways": [
"nuclear hormone receptor transcription",
"molting and developmental timing",
"lipid metabolism and metabolic homeostasis"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning acknowledges that nhr-23 controls molting and that reduced function disrupts development, but then incorrectly concludes that its normal activity supports longevity. In reality, nhr-23 is anti-longevity, meaning its reduction or loss extends lifespan. The model's mechanistic reasoning is also questionable - it classifies the mechanism as \"epigenetic_alterations\" when nhr-23 is primarily a transcription factor involved in developmental timing/molting, not epigenetic reprogramming per se. The model had moderate confidence (0.62) but still got the direction wrong. The reasoning shows some awareness of nhr-23's role in molting but fails to connect this to the known finding that reducing nhr-23 activity extends lifespan in C. elegans.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}