OST3
S. cerevisiae
dolichyl-diphosphooligosaccharide--protein glycotransferase OST3
What the model saw
Gene: OST3 Organism: Saccharomyces cerevisiae Known functions: dolichyl-diphosphooligosaccharide--protein glycotransferase OST3. dolichyl-diphosphooligosaccharide-protein glycotransferase activity. protein binding. protein-disulfide reductase activity.
View unredacted entry
dolichyl-diphosphooligosaccharide--protein glycotransferase OST3. dolichyl-diphosphooligosaccharide-protein glycotransferase activity. protein binding. protein-disulfide reductase activity.
Solver output
OST3 encodes a subunit of the oligosaccharyltransferase (OST) complex in yeast, which catalyzes N-linked glycosylation of nascent proteins in the ER. Proper N-glycosylation is essential for correct protein folding, stability, and quality control — core components of proteostasis. OST3 also possesses a thioredoxin-like domain with protein-disulfide reductase activity, which facilitates disulfide bond rearrangement in substrate glycoproteins, further supporting proper folding in the ER lumen. Loss of OST3 function leads to hypoglycosylation, ER stress, and accumulation of misfolded proteins, which are hallmarks of proteostasis collapse associated with aging. By maintaining efficient N-glycosylation and redox-assisted folding in the secretory pathway, OST3 supports proteostasis and is therefore expected to be pro-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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is logically coherent but leads to the wrong conclusion. OST3 is anti-longevity in yeast, meaning its deletion extends lifespan. The model assumed that because OST3 supports proteostasis and proper glycosylation, it must be pro-longevity, but this is incorrect. In yeast chronological or replicative lifespan studies, deletion of OST3 can extend lifespan, possibly because reduced glycosylation activity triggers beneficial stress responses or reduces ER burden in ways that promote longevity. The model's mechanistic reasoning about proteostasis support is plausible in isolation but fails to account for the actual experimental outcome. The confidence of 0.65 is somewhat moderate but still wrong.
Raw API responses
solver
{
"reasoning": "OST3 encodes a subunit of the oligosaccharyltransferase (OST) complex in yeast, which catalyzes N-linked glycosylation of nascent proteins in the ER. Proper N-glycosylation is essential for correct protein folding, stability, and quality control — core components of proteostasis. OST3 also possesses a thioredoxin-like domain with protein-disulfide reductase activity, which facilitates disulfide bond rearrangement in substrate glycoproteins, further supporting proper folding in the ER lumen. Loss of OST3 function leads to hypoglycosylation, ER stress, and accumulation of misfolded proteins, which are hallmarks of proteostasis collapse associated with aging. By maintaining efficient N-glycosylation and redox-assisted folding in the secretory pathway, OST3 supports proteostasis and is therefore expected to be pro-longevity.",
"confidence": 0.65,
"key_pathways": [
"N-linked glycosylation / oligosaccharyltransferase complex",
"ER protein quality control and proteostasis",
"Protein-disulfide reductase / thioredoxin-like folding assistance"
],
"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 is logically coherent but leads to the wrong conclusion. OST3 is anti-longevity in yeast, meaning its deletion extends lifespan. The model assumed that because OST3 supports proteostasis and proper glycosylation, it must be pro-longevity, but this is incorrect. In yeast chronological or replicative lifespan studies, deletion of OST3 can extend lifespan, possibly because reduced glycosylation activity triggers beneficial stress responses or reduces ER burden in ways that promote longevity. The model's mechanistic reasoning about proteostasis support is plausible in isolation but fails to account for the actual experimental outcome. The confidence of 0.65 is somewhat moderate but still wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}