nhr-14
C. elegans
Nuclear hormone receptor family member nhr-14
What the model saw
Gene: nhr-14 Organism: Caenorhabditis elegans Known functions: Nuclear hormone receptor family member nhr-14. DNA-binding transcription factor activity. RNA polymerase II cis-regulatory region sequence-specific DNA binding. nuclear receptor activity. sequence-specific DNA binding. steroid hormone binding. zinc ion binding.
View unredacted entry
Nuclear hormone receptor family member nhr-14. DNA-binding transcription factor activity. RNA polymerase II cis-regulatory region sequence-specific DNA binding. nuclear receptor activity. sequence-specific DNA binding. steroid hormone binding. zinc ion binding.
Solver output
nhr-14 is a C. elegans nuclear hormone receptor (NHR) family member with steroid hormone binding, zinc ion binding (zinc finger DNA-binding domain), and sequence-specific DNA binding at RNA Pol II cis-regulatory regions. NHRs in C. elegans are orthologous to mammalian nuclear receptors involved in lipid/metabolic sensing; nhr-14 is the closest homolog of the human thyroid hormone receptor (TR/THRA). Thyroid hormone receptor signaling modulates metabolic rate, mitochondrial biogenesis, and energy homeostasis — pathways tightly linked to the deregulated nutrient-sensing hallmark of aging. In C. elegans, nuclear hormone receptors in this subfamily (e.g., nhr-49, nhr-80) that regulate fatty acid metabolism and mitochondrial function tend to promote longevity when active. As a transcriptional regulator of steroid/hormone-responsive metabolic gene networks, nhr-14's normal function is most consistent with maintaining metabolic homeostasis, which would support longevity. However, the specific downstream targets of nhr-14 are not fully characterized, introducing some uncertainty.
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 relied on analogies to related NHRs (nhr-49, nhr-80) that promote longevity, but nhr-14 has the opposite effect. The model acknowledged uncertainty (confidence 0.52) but still got the direction wrong. The mechanistic reasoning about thyroid hormone receptor homology and metabolic homeostasis was speculative and ultimately incorrect. The model's low confidence is appropriate given the uncertainty, but the prediction itself was wrong.
Raw API responses
solver
{
"reasoning": "nhr-14 is a C. elegans nuclear hormone receptor (NHR) family member with steroid hormone binding, zinc ion binding (zinc finger DNA-binding domain), and sequence-specific DNA binding at RNA Pol II cis-regulatory regions. NHRs in C. elegans are orthologous to mammalian nuclear receptors involved in lipid/metabolic sensing; nhr-14 is the closest homolog of the human thyroid hormone receptor (TR/THRA). Thyroid hormone receptor signaling modulates metabolic rate, mitochondrial biogenesis, and energy homeostasis — pathways tightly linked to the deregulated nutrient-sensing hallmark of aging. In C. elegans, nuclear hormone receptors in this subfamily (e.g., nhr-49, nhr-80) that regulate fatty acid metabolism and mitochondrial function tend to promote longevity when active. As a transcriptional regulator of steroid/hormone-responsive metabolic gene networks, nhr-14's normal function is most consistent with maintaining metabolic homeostasis, which would support longevity. However, the specific downstream targets of nhr-14 are not fully characterized, introducing some uncertainty.",
"confidence": 0.52,
"key_pathways": [
"nuclear hormone receptor / steroid hormone signaling",
"deregulated nutrient and metabolic sensing",
"RNA Pol II transcriptional regulation of metabolic genes"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning relied on analogies to related NHRs (nhr-49, nhr-80) that promote longevity, but nhr-14 has the opposite effect. The model acknowledged uncertainty (confidence 0.52) but still got the direction wrong. The mechanistic reasoning about thyroid hormone receptor homology and metabolic homeostasis was speculative and ultimately incorrect. The model's low confidence is appropriate given the uncertainty, but the prediction itself was wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}