aha-1
C. elegans
Aryl hydrocarbon receptor nuclear translocator homolog
What the model saw
Gene: aha-1 Organism: Caenorhabditis elegans Known functions: Aryl hydrocarbon receptor nuclear translocator homolog. DNA binding. DNA-binding transcription factor activity. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II-specific DNA-binding transcription factor binding. protein binding. protein dimerization activity. sequence-specific DNA binding.
View unredacted entry
Aryl hydrocarbon receptor nuclear translocator homolog. DNA binding. DNA-binding transcription factor activity. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II-specific DNA-binding transcription factor binding. protein binding. protein dimerization activity. sequence-specific DNA binding.
Solver output
AHA-1 is the C. elegans homolog of ARNT (Aryl Hydrocarbon Receptor Nuclear Translocator), a bHLH-PAS domain transcription factor that acts as an obligate dimerization partner for HIF-1 (hypoxia-inducible factor) and AHR-1 (aryl hydrocarbon receptor). In C. elegans, the AHA-1/HIF-1 heterodimer regulates transcriptional responses to hypoxia and metabolic stress, pathways closely linked to nutrient sensing and mitochondrial function. HIF-1 signaling in C. elegans has been shown to interact with the DAF-2/insulin-IGF-1 pathway; loss of hif-1 can extend lifespan in certain genetic backgrounds, but aha-1 as the ARNT partner also supports transcriptional programs that promote stress adaptation. The protein dimerization activity is essential for forming functional transcription factor complexes that drive expression of cytoprotective and metabolic genes. Because AHA-1 is required for HIF-1-dependent transcription, and HIF-1 activity in C. elegans can promote longevity under certain conditions (e.g., mild hypoxia or interaction with DAF-16), AHA-1 is tentatively pro-longevity, though context-dependency introduces 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 correctly predicted pro_longevity for aha-1. The mechanistic reasoning is sound - AHA-1 as the ARNT homolog dimerizes with HIF-1 to regulate hypoxia-responsive transcription, and this pathway is linked to longevity in C. elegans. The model appropriately notes context-dependency and uncertainty (confidence 0.62). The mechanism class "deregulated_nutrient_sensing" is a reasonable but imperfect fit - hypoxia/HIF signaling is more directly relevant than nutrient sensing per se, though the two pathways do interact. The reasoning about HIF-1/AHA-1 heterodimer formation and its role in stress adaptation and longevity is mechanistically plausible and well-articulated.
Raw API responses
solver
{
"reasoning": "AHA-1 is the C. elegans homolog of ARNT (Aryl Hydrocarbon Receptor Nuclear Translocator), a bHLH-PAS domain transcription factor that acts as an obligate dimerization partner for HIF-1 (hypoxia-inducible factor) and AHR-1 (aryl hydrocarbon receptor). In C. elegans, the AHA-1/HIF-1 heterodimer regulates transcriptional responses to hypoxia and metabolic stress, pathways closely linked to nutrient sensing and mitochondrial function. HIF-1 signaling in C. elegans has been shown to interact with the DAF-2/insulin-IGF-1 pathway; loss of hif-1 can extend lifespan in certain genetic backgrounds, but aha-1 as the ARNT partner also supports transcriptional programs that promote stress adaptation. The protein dimerization activity is essential for forming functional transcription factor complexes that drive expression of cytoprotective and metabolic genes. Because AHA-1 is required for HIF-1-dependent transcription, and HIF-1 activity in C. elegans can promote longevity under certain conditions (e.g., mild hypoxia or interaction with DAF-16), AHA-1 is tentatively pro-longevity, though context-dependency introduces uncertainty.",
"confidence": 0.62,
"key_pathways": [
"HIF-1/AHA-1 hypoxia signaling",
"DAF-2/insulin-IGF-1 nutrient sensing pathway",
"bHLH-PAS transcription factor dimerization"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for aha-1. The mechanistic reasoning is sound - AHA-1 as the ARNT homolog dimerizes with HIF-1 to regulate hypoxia-responsive transcription, and this pathway is linked to longevity in C. elegans. The model appropriately notes context-dependency and uncertainty (confidence 0.62). The mechanism class \"deregulated_nutrient_sensing\" is a reasonable but imperfect fit - hypoxia/HIF signaling is more directly relevant than nutrient sensing per se, though the two pathways do interact. The reasoning about HIF-1/AHA-1 heterodimer formation and its role in stress adaptation and longevity is mechanistically plausible and well-articulated.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}