mans-1
C. elegans
alpha-1,2-Mannosidase
What the model saw
Gene: mans-1 Organism: Caenorhabditis elegans Known functions: alpha-1,2-Mannosidase. calcium ion binding. mannosyl-oligosaccharide 1,2-alpha-mannosidase activity.
View unredacted entry
alpha-1,2-Mannosidase. calcium ion binding. mannosyl-oligosaccharide 1,2-alpha-mannosidase activity.
Solver output
mans-1 encodes an alpha-1,2-mannosidase that trims mannose residues from N-linked glycan precursors in the endoplasmic reticulum (ER), a critical step in the N-glycan processing pathway. Proper N-glycan trimming by ER mannosidases is required for correct glycoprotein folding, quality control, and ER-associated degradation (ERAD) of misfolded proteins. By facilitating the maturation and quality control of glycoproteins, mans-1 supports proteostasis. Loss of this activity would impair glycoprotein folding fidelity, increase ER stress, and compromise ERAD, all of which are associated with accelerated aging and reduced lifespan in C. elegans. The calcium ion binding activity is consistent with the known calcium dependence of ER-resident mannosidases, reinforcing its role in the ER proteostasis network.
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 assumes that mans-1 supports proteostasis and that loss of function would be harmful (implying the gene is pro-longevity). However, the ground truth indicates mans-1 is anti_longevity, meaning its activity actually reduces lifespan (or its loss extends lifespan). The mechanistic reasoning is plausible in general terms about N-glycan processing, but the model drew the wrong directional conclusion about the gene's effect on longevity. The model was moderately confident (0.62) in the wrong direction. The mechanism class of "loss_of_proteostasis" is also incorrect given the anti_longevity classification.
Raw API responses
solver
{
"reasoning": "mans-1 encodes an alpha-1,2-mannosidase that trims mannose residues from N-linked glycan precursors in the endoplasmic reticulum (ER), a critical step in the N-glycan processing pathway. Proper N-glycan trimming by ER mannosidases is required for correct glycoprotein folding, quality control, and ER-associated degradation (ERAD) of misfolded proteins. By facilitating the maturation and quality control of glycoproteins, mans-1 supports proteostasis. Loss of this activity would impair glycoprotein folding fidelity, increase ER stress, and compromise ERAD, all of which are associated with accelerated aging and reduced lifespan in C. elegans. The calcium ion binding activity is consistent with the known calcium dependence of ER-resident mannosidases, reinforcing its role in the ER proteostasis network.",
"confidence": 0.62,
"key_pathways": [
"N-glycan processing / ER quality control",
"ER-associated degradation (ERAD)",
"Unfolded protein response (UPR)"
],
"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 assumes that mans-1 supports proteostasis and that loss of function would be harmful (implying the gene is pro-longevity). However, the ground truth indicates mans-1 is anti_longevity, meaning its activity actually reduces lifespan (or its loss extends lifespan). The mechanistic reasoning is plausible in general terms about N-glycan processing, but the model drew the wrong directional conclusion about the gene's effect on longevity. The model was moderately confident (0.62) in the wrong direction. The mechanism class of \"loss_of_proteostasis\" is also incorrect given the anti_longevity classification.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}