rpn-6.1
C. elegans
putative 26S proteasome regulatory subunit rpn-6.1
What the model saw
Gene: rpn-6.1 Organism: Caenorhabditis elegans Known functions: putative 26S proteasome regulatory subunit rpn-6.1. structural molecule activity.
View unredacted entry
putative 26S proteasome regulatory subunit rpn-6.1. structural molecule activity.
Solver output
rpn-6.1 encodes a structural subunit of the 19S regulatory particle (lid) of the 26S proteasome in C. elegans. The 26S proteasome is the central machinery for ubiquitin-dependent protein degradation, and its activity is essential for maintaining proteostasis by clearing misfolded, damaged, and aggregated proteins. Upregulation of rpn-6.1 has been shown to enhance proteasome assembly and activity, which is a downstream effector of DAF-16/FOXO transcription factor in the insulin/IGF-1 signaling pathway, directly linking it to longevity. Increased proteasome capacity reduces the accumulation of proteotoxic aggregates that drive aging pathology. Loss of rpn-6.1 function impairs proteasome activity and accelerates aging phenotypes, while overexpression extends lifespan in C. elegans. Thus, the normal function of rpn-6.1 in sustaining 26S proteasome integrity promotes proteostasis and longevity.
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 rpn-6.1. The mechanistic reasoning is accurate and detailed: rpn-6.1 is indeed a 19S regulatory particle subunit of the 26S proteasome, its overexpression extends lifespan in C. elegans, it is a downstream target of DAF-16/FOXO, and it promotes proteostasis. The model correctly identifies the key pathways involved. High confidence (0.82) is appropriate given the well-established literature on this gene. The reasoning is thorough and mechanistically sound.
Raw API responses
solver
{
"reasoning": "rpn-6.1 encodes a structural subunit of the 19S regulatory particle (lid) of the 26S proteasome in C. elegans. The 26S proteasome is the central machinery for ubiquitin-dependent protein degradation, and its activity is essential for maintaining proteostasis by clearing misfolded, damaged, and aggregated proteins. Upregulation of rpn-6.1 has been shown to enhance proteasome assembly and activity, which is a downstream effector of DAF-16/FOXO transcription factor in the insulin/IGF-1 signaling pathway, directly linking it to longevity. Increased proteasome capacity reduces the accumulation of proteotoxic aggregates that drive aging pathology. Loss of rpn-6.1 function impairs proteasome activity and accelerates aging phenotypes, while overexpression extends lifespan in C. elegans. Thus, the normal function of rpn-6.1 in sustaining 26S proteasome integrity promotes proteostasis and longevity.",
"confidence": 0.82,
"key_pathways": [
"26S proteasome assembly and activity",
"DAF-16/FOXO insulin/IGF-1 signaling",
"ubiquitin-proteasome proteostasis"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for rpn-6.1. The mechanistic reasoning is accurate and detailed: rpn-6.1 is indeed a 19S regulatory particle subunit of the 26S proteasome, its overexpression extends lifespan in C. elegans, it is a downstream target of DAF-16/FOXO, and it promotes proteostasis. The model correctly identifies the key pathways involved. High confidence (0.82) is appropriate given the well-established literature on this gene. The reasoning is thorough and mechanistically sound.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}