cdc-48.1
C. elegans
Transitional endoplasmic reticulum ATPase homolog 1
What the model saw
Gene: cdc-48.1 Organism: Caenorhabditis elegans Known functions: Transitional endoplasmic reticulum ATPase homolog 1. ATP binding. ATP hydrolysis activity. hydrolase activity. identical protein binding. polyubiquitin modification-dependent protein binding. protein binding. protein-containing complex binding.
View unredacted entry
Transitional endoplasmic reticulum ATPase homolog 1. ATP binding. ATP hydrolysis activity. hydrolase activity. identical protein binding. polyubiquitin modification-dependent protein binding. protein binding. protein-containing complex binding.
Solver output
CDC-48.1 is the C. elegans homolog of p97/VCP (transitional endoplasmic reticulum ATPase), a AAA+ ATPase central to ubiquitin-dependent protein quality control. Its polyubiquitin modification-dependent protein binding and ATP hydrolysis activity enable it to extract and unfold ubiquitinated substrates from membranes, chromatin, and protein complexes, routing them to the proteasome for degradation. This function is essential for ER-associated degradation (ERAD), mitophagy receptor extraction, and clearance of misfolded or aggregated proteins. By maintaining proteostasis and preventing accumulation of toxic protein aggregates—a hallmark of aging—CDC-48.1 activity is expected to promote longevity. Loss of p97/CDC-48 function in model organisms leads to accelerated proteotoxic stress and shortened lifespan, consistent with a pro-longevity role for the wild-type gene.
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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about CDC-48.1/p97/VCP's role in proteostasis, ERAD, and ubiquitin-dependent protein quality control is mechanistically plausible and well-articulated, but it led to the wrong conclusion. The model assumed that because p97/VCP maintains proteostasis, it must be pro-longevity. However, in C. elegans, cdc-48.1 is classified as anti_longevity, meaning its activity actually limits lifespan. This could be because CDC-48.1 may also extract and degrade proteins that are beneficial for longevity (e.g., stress response factors, autophagy components), or it may promote aging through other mechanisms. The model was fairly confident (0.78) in its wrong answer. The mechanistic reasoning, while coherent, was incomplete and missed the anti-longevity aspects of this gene's function in C. elegans.
Raw API responses
solver
{
"reasoning": "CDC-48.1 is the C. elegans homolog of p97/VCP (transitional endoplasmic reticulum ATPase), a AAA+ ATPase central to ubiquitin-dependent protein quality control. Its polyubiquitin modification-dependent protein binding and ATP hydrolysis activity enable it to extract and unfold ubiquitinated substrates from membranes, chromatin, and protein complexes, routing them to the proteasome for degradation. This function is essential for ER-associated degradation (ERAD), mitophagy receptor extraction, and clearance of misfolded or aggregated proteins. By maintaining proteostasis and preventing accumulation of toxic protein aggregates—a hallmark of aging—CDC-48.1 activity is expected to promote longevity. Loss of p97/CDC-48 function in model organisms leads to accelerated proteotoxic stress and shortened lifespan, consistent with a pro-longevity role for the wild-type gene.",
"confidence": 0.78,
"key_pathways": [
"ubiquitin-proteasome system (ERAD/p97-UFD1-NPL4 pathway)",
"protein quality control and proteostasis",
"autophagy receptor extraction and mitophagy"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about CDC-48.1/p97/VCP's role in proteostasis, ERAD, and ubiquitin-dependent protein quality control is mechanistically plausible and well-articulated, but it led to the wrong conclusion. The model assumed that because p97/VCP maintains proteostasis, it must be pro-longevity. However, in C. elegans, cdc-48.1 is classified as anti_longevity, meaning its activity actually limits lifespan. This could be because CDC-48.1 may also extract and degrade proteins that are beneficial for longevity (e.g., stress response factors, autophagy components), or it may promote aging through other mechanisms. The model was fairly confident (0.78) in its wrong answer. The mechanistic reasoning, while coherent, was incomplete and missed the anti-longevity aspects of this gene's function in C. elegans.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}