pha-4
C. elegans
Defective pharyngeal development protein 4
What the model saw
Gene: pha-4 Organism: Caenorhabditis elegans Known functions: Defective pharyngeal development protein 4. 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. sequence-specific DNA binding.
View unredacted entry
Defective pharyngeal development protein 4. 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. sequence-specific DNA binding.
Solver output
pha-4 encodes the C. elegans FOXA (forkhead box A) transcription factor, which functions as a sequence-specific DNA-binding transcription factor acting via RNA Pol II-dependent cis-regulatory elements. It is the master regulator of the transcriptional response to dietary restriction (DR) in C. elegans: pha-4 is required for the lifespan extension conferred by dietary restriction, acting downstream of the TOR/nutrient-sensing pathway to upregulate autophagy genes and stress-response targets. Loss of pha-4 abolishes DR-mediated longevity, while its activity promotes expression of autophagy and metabolic adaptation genes that extend lifespan. This places pha-4 squarely within the deregulated nutrient-sensing hallmark, specifically as a transcriptional effector of the DR–TOR axis.
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 identified pha-4 as pro_longevity with high confidence (0.93). The mechanistic reasoning is accurate and detailed: pha-4 encodes the C. elegans FOXA transcription factor, is required for dietary restriction-mediated lifespan extension, acts downstream of TOR/nutrient-sensing, and regulates autophagy and stress-response genes. The mechanism class of "deregulated_nutrient_sensing" is appropriate. The reasoning aligns well with published literature on pha-4's role in longevity.
Raw API responses
solver
{
"reasoning": "pha-4 encodes the C. elegans FOXA (forkhead box A) transcription factor, which functions as a sequence-specific DNA-binding transcription factor acting via RNA Pol II-dependent cis-regulatory elements. It is the master regulator of the transcriptional response to dietary restriction (DR) in C. elegans: pha-4 is required for the lifespan extension conferred by dietary restriction, acting downstream of the TOR/nutrient-sensing pathway to upregulate autophagy genes and stress-response targets. Loss of pha-4 abolishes DR-mediated longevity, while its activity promotes expression of autophagy and metabolic adaptation genes that extend lifespan. This places pha-4 squarely within the deregulated nutrient-sensing hallmark, specifically as a transcriptional effector of the DR–TOR axis.",
"confidence": 0.93,
"key_pathways": [
"dietary restriction / TOR nutrient-sensing pathway",
"FOXA transcription factor-mediated autophagy gene regulation",
"RNA polymerase II transcriptional response to caloric restriction"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified pha-4 as pro_longevity with high confidence (0.93). The mechanistic reasoning is accurate and detailed: pha-4 encodes the C. elegans FOXA transcription factor, is required for dietary restriction-mediated lifespan extension, acts downstream of TOR/nutrient-sensing, and regulates autophagy and stress-response genes. The mechanism class of \"deregulated_nutrient_sensing\" is appropriate. The reasoning aligns well with published literature on pha-4's role in longevity.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}