mdt-15
C. elegans
Mediator of RNA polymerase II transcription subunit 15
What the model saw
Gene: mdt-15 Organism: Caenorhabditis elegans Known functions: Mediator of RNA polymerase II transcription subunit 15. nuclear receptor binding. protein binding. transcription coactivator activity. transcription coregulator activity.
View unredacted entry
Mediator of RNA polymerase II transcription subunit 15. nuclear receptor binding. protein binding. transcription coactivator activity. transcription coregulator activity.
Solver output
MDT-15 is a subunit of the Mediator complex that acts as a transcriptional coactivator by binding nuclear receptors, including NHR-49 (the C. elegans HNF4α ortholog) and SKN-1 (Nrf ortholog). Through these interactions, MDT-15 co-activates transcription of genes involved in fatty acid desaturation, β-oxidation, and xenobiotic/oxidative stress responses. Loss of mdt-15 impairs lipid homeostasis and reduces stress resistance, both of which are associated with shortened lifespan in C. elegans. Its role as a coactivator of SKN-1 target genes links it directly to the IIS/DAF-16 and oxidative stress response pathways that are central to longevity regulation. Because MDT-15 enables adaptive transcriptional responses to nutrient and metabolic signals, its normal function supports healthspan and lifespan extension rather than opposing it.
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 mdt-15 in C. elegans. The mechanistic reasoning is detailed and accurate: MDT-15 is indeed a Mediator complex subunit that co-activates NHR-49 and SKN-1 target genes involved in fatty acid metabolism and oxidative stress responses. The model correctly identifies that loss of mdt-15 impairs lipid homeostasis and stress resistance, leading to shortened lifespan, making it pro-longevity in its normal function. The mechanism classification of "deregulated_nutrient_sensing" is reasonable given MDT-15's role in metabolic/nutrient-responsive transcription. Confidence of 0.72 is appropriate.
Raw API responses
solver
{
"reasoning": "MDT-15 is a subunit of the Mediator complex that acts as a transcriptional coactivator by binding nuclear receptors, including NHR-49 (the C. elegans HNF4α ortholog) and SKN-1 (Nrf ortholog). Through these interactions, MDT-15 co-activates transcription of genes involved in fatty acid desaturation, β-oxidation, and xenobiotic/oxidative stress responses. Loss of mdt-15 impairs lipid homeostasis and reduces stress resistance, both of which are associated with shortened lifespan in C. elegans. Its role as a coactivator of SKN-1 target genes links it directly to the IIS/DAF-16 and oxidative stress response pathways that are central to longevity regulation. Because MDT-15 enables adaptive transcriptional responses to nutrient and metabolic signals, its normal function supports healthspan and lifespan extension rather than opposing it.",
"confidence": 0.72,
"key_pathways": [
"NHR-49/fatty acid metabolism and lipid homeostasis",
"SKN-1/Nrf oxidative stress response",
"Mediator complex transcriptional coactivation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for mdt-15 in C. elegans. The mechanistic reasoning is detailed and accurate: MDT-15 is indeed a Mediator complex subunit that co-activates NHR-49 and SKN-1 target genes involved in fatty acid metabolism and oxidative stress responses. The model correctly identifies that loss of mdt-15 impairs lipid homeostasis and stress resistance, leading to shortened lifespan, making it pro-longevity in its normal function. The mechanism classification of \"deregulated_nutrient_sensing\" is reasonable given MDT-15's role in metabolic/nutrient-responsive transcription. Confidence of 0.72 is appropriate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}