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nhr-154

C. elegans

Nuclear hormone receptor family member nhr-154

What the model saw

Gene: nhr-154
Organism: Caenorhabditis elegans
Known functions: Nuclear hormone receptor family member nhr-154. 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-154. 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

Predicted influence
Unclear
Confidence
35%
Mechanism
Deregulated nutrient sensing
Reasoning

NHR-154 is a member of the nuclear hormone receptor (NHR) superfamily in C. elegans, which encompasses a large and functionally diverse family of ligand-activated transcription factors. While some NHRs in C. elegans (e.g., DAF-12, NHR-49) are well-characterized regulators of longevity through lipid metabolism and nutrient sensing pathways, NHR-154 is a poorly characterized family member. Its molecular functions — sequence-specific DNA binding via zinc finger domains, nuclear receptor activity, and RNA Pol II cis-regulatory region binding — are consistent with transcriptional regulation, but without knowledge of its specific target genes or ligands, the direction of its effect on lifespan cannot be confidently determined. Nuclear hormone receptors can act as either pro- or anti-longevity factors depending on their downstream transcriptional programs, making this prediction genuinely ambiguous based solely on the available annotations.

Key pathways
nuclear hormone receptor signalingRNA polymerase II transcriptional regulationzinc finger DNA binding
Longevity influence
Anti-longevity
Lifespan effect
Increase

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

Answer
Incorrect
Mechanism
Incorrect
Reasoning quality
3/5
Failure mode
Appropriately uncertain
Notes

The model predicted "unclear" while the ground truth is "anti_longevity." The model's reasoning is sound given the limited information provided — NHR-154 is indeed a poorly characterized nuclear hormone receptor, and the model correctly notes that NHRs can be either pro- or anti-longevity. The model's uncertainty is genuine and well-reasoned, but it still got the answer wrong. The mechanism class of "deregulated_nutrient_sensing" is speculative and not confirmed. This is a case of appropriate uncertainty rather than a confident wrong answer, but the prediction still fails to match the ground truth.

Raw API responses

solver

{
  "reasoning": "NHR-154 is a member of the nuclear hormone receptor (NHR) superfamily in C. elegans, which encompasses a large and functionally diverse family of ligand-activated transcription factors. While some NHRs in C. elegans (e.g., DAF-12, NHR-49) are well-characterized regulators of longevity through lipid metabolism and nutrient sensing pathways, NHR-154 is a poorly characterized family member. Its molecular functions — sequence-specific DNA binding via zinc finger domains, nuclear receptor activity, and RNA Pol II cis-regulatory region binding — are consistent with transcriptional regulation, but without knowledge of its specific target genes or ligands, the direction of its effect on lifespan cannot be confidently determined. Nuclear hormone receptors can act as either pro- or anti-longevity factors depending on their downstream transcriptional programs, making this prediction genuinely ambiguous based solely on the available annotations.",
  "confidence": 0.35,
  "key_pathways": [
    "nuclear hormone receptor signaling",
    "RNA polymerase II transcriptional regulation",
    "zinc finger DNA binding"
  ],
  "mechanism_class": "deregulated_nutrient_sensing",
  "longevity_influence": "unclear"
}

advisor

{
  "notes": "The model predicted \"unclear\" while the ground truth is \"anti_longevity.\" The model's reasoning is sound given the limited information provided — NHR-154 is indeed a poorly characterized nuclear hormone receptor, and the model correctly notes that NHRs can be either pro- or anti-longevity. The model's uncertainty is genuine and well-reasoned, but it still got the answer wrong. The mechanism class of \"deregulated_nutrient_sensing\" is speculative and not confirmed. This is a case of appropriate uncertainty rather than a confident wrong answer, but the prediction still fails to match the ground truth.",
  "failure_mode": "appropriately_uncertain",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 3,
  "ground_truth_questionable": false
}