nhr-25
C. elegans
Nuclear hormone receptor family member nhr-25
What the model saw
Gene: nhr-25 Organism: Caenorhabditis elegans Known functions: Nuclear hormone receptor family member nhr-25. DNA binding. DNA-binding transcription factor activity. RNA polymerase II cis-regulatory region sequence-specific DNA binding. armadillo repeat domain binding. nuclear receptor activity. protein binding. sequence-specific DNA binding. zinc ion binding.
View unredacted entry
Nuclear hormone receptor family member nhr-25. DNA binding. DNA-binding transcription factor activity. RNA polymerase II cis-regulatory region sequence-specific DNA binding. armadillo repeat domain binding. nuclear receptor activity. protein binding. sequence-specific DNA binding. zinc ion binding.
Solver output
NHR-25 is the C. elegans ortholog of mammalian NR5A (SF-1/LRH-1) nuclear hormone receptors, which act as ligand-activated transcription factors regulating developmental and metabolic gene programs. As a nuclear receptor with sequence-specific DNA binding and RNA Pol II cis-regulatory activity, NHR-25 modulates transcriptional programs governing molting, lipid metabolism, and steroid hormone signaling. Its armadillo repeat domain binding suggests interaction with Wnt/β-catenin pathway components, linking it to stem cell maintenance and tissue homeostasis. Nuclear hormone receptors in C. elegans, particularly those in the NR5A family, have been implicated in DAF-16/FOXO-adjacent transcriptional regulation and lipid homeostasis pathways that influence lifespan. The zinc ion binding is consistent with its C4 zinc finger DNA-binding domain, a hallmark of nuclear receptors that coordinate transcriptional reprogramming relevant to aging; proper NHR-25 activity supports epigenetic and transcriptional homeostasis that generally favors longevity.
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 pro_longevity for nhr-25. However, the mechanistic reasoning is speculative and partially incorrect. The model classifies the mechanism as "epigenetic_alterations," which is not well-supported. NHR-25 is primarily known for its role in molting, cuticle development, and lipid metabolism as a transcription factor — not epigenetic alterations per se. The reasoning about "DAF-16/FOXO-adjacent transcriptional regulation" is vague and not well-established for NHR-25 specifically. The connection to Wnt/β-catenin via armadillo repeat domain binding is plausible but speculative. The model's confidence of 0.55 is appropriately modest. The correct answer was reached, but the mechanistic reasoning is largely inferential and not grounded in specific experimental evidence about nhr-25's role in longevity.
Raw API responses
solver
{
"reasoning": "NHR-25 is the C. elegans ortholog of mammalian NR5A (SF-1/LRH-1) nuclear hormone receptors, which act as ligand-activated transcription factors regulating developmental and metabolic gene programs. As a nuclear receptor with sequence-specific DNA binding and RNA Pol II cis-regulatory activity, NHR-25 modulates transcriptional programs governing molting, lipid metabolism, and steroid hormone signaling. Its armadillo repeat domain binding suggests interaction with Wnt/β-catenin pathway components, linking it to stem cell maintenance and tissue homeostasis. Nuclear hormone receptors in C. elegans, particularly those in the NR5A family, have been implicated in DAF-16/FOXO-adjacent transcriptional regulation and lipid homeostasis pathways that influence lifespan. The zinc ion binding is consistent with its C4 zinc finger DNA-binding domain, a hallmark of nuclear receptors that coordinate transcriptional reprogramming relevant to aging; proper NHR-25 activity supports epigenetic and transcriptional homeostasis that generally favors longevity.",
"confidence": 0.55,
"key_pathways": [
"nuclear hormone receptor / steroid signaling",
"lipid metabolism and homeostasis",
"Wnt/armadillo transcriptional regulation"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for nhr-25. However, the mechanistic reasoning is speculative and partially incorrect. The model classifies the mechanism as \"epigenetic_alterations,\" which is not well-supported. NHR-25 is primarily known for its role in molting, cuticle development, and lipid metabolism as a transcription factor — not epigenetic alterations per se. The reasoning about \"DAF-16/FOXO-adjacent transcriptional regulation\" is vague and not well-established for NHR-25 specifically. The connection to Wnt/β-catenin via armadillo repeat domain binding is plausible but speculative. The model's confidence of 0.55 is appropriately modest. The correct answer was reached, but the mechanistic reasoning is largely inferential and not grounded in specific experimental evidence about nhr-25's role in longevity.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}