nhr-49
C. elegans
NR LBD domain-containing protein;Nuclear hormone receptor family member nhr-49
What the model saw
Gene: nhr-49 Organism: Caenorhabditis elegans Known functions: NR LBD domain-containing protein;Nuclear hormone receptor family member nhr-49. DNA-binding transcription factor activity. DNA-binding transcription factor binding. RNA polymerase II cis-regulatory region sequence-specific DNA binding. nuclear receptor activity. protein binding. sequence-specific DNA binding. zinc ion binding.
View unredacted entry
NR LBD domain-containing protein;Nuclear hormone receptor family member nhr-49. DNA-binding transcription factor activity. DNA-binding transcription factor binding. RNA polymerase II cis-regulatory region sequence-specific DNA binding. nuclear receptor activity. protein binding. sequence-specific DNA binding. zinc ion binding.
Solver output
NHR-49 is the C. elegans ortholog of mammalian HNF4α/PPARα, a nuclear hormone receptor that functions as a master transcriptional regulator of fatty acid metabolism and mitochondrial β-oxidation. By binding DNA at cis-regulatory elements via its zinc finger domain and interacting with co-regulators, NHR-49 activates genes involved in fatty acid desaturation and oxidation, maintaining lipid homeostasis. Loss of nhr-49 in C. elegans leads to fat accumulation, reduced expression of β-oxidation genes, and shortened lifespan, while its activity is required for the lifespan extension seen under dietary restriction and in certain mitochondrial mutants. NHR-49 also cooperates with NHR-80 to regulate oleic acid desaturation, a pathway linked to membrane fluidity and longevity. Its role in coordinating nutrient-sensing transcriptional programs places it squarely within the deregulated nutrient-sensing hallmark 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 correctly predicted nhr-49 as pro_longevity with high confidence (0.82). The mechanistic reasoning is excellent and accurate: NHR-49 is indeed the C. elegans ortholog of HNF4α/PPARα, functions as a master transcriptional regulator of fatty acid metabolism and β-oxidation, loss leads to fat accumulation and shortened lifespan, and it is required for dietary restriction-mediated lifespan extension. The cooperation with NHR-80 for oleic acid desaturation is also correctly noted. The mechanism class of "deregulated_nutrient_sensing" is appropriate given NHR-49's role in lipid metabolism and nutrient-sensing transcriptional programs. All key pathways identified are relevant and accurate.
Raw API responses
solver
{
"reasoning": "NHR-49 is the C. elegans ortholog of mammalian HNF4α/PPARα, a nuclear hormone receptor that functions as a master transcriptional regulator of fatty acid metabolism and mitochondrial β-oxidation. By binding DNA at cis-regulatory elements via its zinc finger domain and interacting with co-regulators, NHR-49 activates genes involved in fatty acid desaturation and oxidation, maintaining lipid homeostasis. Loss of nhr-49 in C. elegans leads to fat accumulation, reduced expression of β-oxidation genes, and shortened lifespan, while its activity is required for the lifespan extension seen under dietary restriction and in certain mitochondrial mutants. NHR-49 also cooperates with NHR-80 to regulate oleic acid desaturation, a pathway linked to membrane fluidity and longevity. Its role in coordinating nutrient-sensing transcriptional programs places it squarely within the deregulated nutrient-sensing hallmark of aging.",
"confidence": 0.82,
"key_pathways": [
"fatty acid beta-oxidation / lipid homeostasis",
"dietary restriction-mediated lifespan extension",
"nuclear hormone receptor / PPAR-alpha signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted nhr-49 as pro_longevity with high confidence (0.82). The mechanistic reasoning is excellent and accurate: NHR-49 is indeed the C. elegans ortholog of HNF4α/PPARα, functions as a master transcriptional regulator of fatty acid metabolism and β-oxidation, loss leads to fat accumulation and shortened lifespan, and it is required for dietary restriction-mediated lifespan extension. The cooperation with NHR-80 for oleic acid desaturation is also correctly noted. The mechanism class of \"deregulated_nutrient_sensing\" is appropriate given NHR-49's role in lipid metabolism and nutrient-sensing transcriptional programs. All key pathways identified are relevant and accurate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}