y71h2ar.2
C. elegans
Peptidase C1A papain C-terminal domain-containing protein
What the model saw
Gene: Y71H2AR.2 Organism: Caenorhabditis elegans Known functions: Peptidase C1A papain C-terminal domain-containing protein. cysteine-type endopeptidase activity. cysteine-type peptidase activity.
View unredacted entry
Peptidase C1A papain C-terminal domain-containing protein. cysteine-type endopeptidase activity. cysteine-type peptidase activity.
Solver output
Y71H2AR.2 encodes a papain-family (C1A) cysteine protease, a class of lysosomal cathepsins that are essential effectors of autophagy and lysosomal protein degradation. In C. elegans, lysosomal cysteine proteases (e.g., CPL-1/cathepsin L) are required for autophagic flux and proteostasis maintenance, both of which are critical for normal lifespan. Loss of such proteases impairs the clearance of damaged proteins and organelles, accelerating aging phenotypes. The papain C-terminal domain is the hallmark of lysosomal cathepsins, placing this gene squarely in the autophagy-lysosome degradation axis. Functional activity of this protease therefore supports proteostasis and autophagic clearance, promoting longevity 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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumes that lysosomal cysteine proteases (cathepsins) are generally pro-longevity because they support autophagy and proteostasis. However, Y71H2AR.2 is actually anti-longevity, meaning its activity shortens lifespan (i.e., loss of function likely extends lifespan). This is consistent with some C. elegans cysteine proteases that, when knocked down, extend lifespan - possibly through mechanisms like reduced protein degradation that paradoxically benefits longevity, or through roles in pathways that limit lifespan. The model's mechanistic reasoning is plausible in general terms for cathepsin biology but is incorrect for this specific gene. The model was moderately confident (0.62) in the wrong direction. The mechanism class "disabled_macroautophagy" is also inconsistent with the model's own reasoning (which argues the gene promotes autophagy, not disables it), suggesting an internal inconsistency in the prediction.
Raw API responses
solver
{
"reasoning": "Y71H2AR.2 encodes a papain-family (C1A) cysteine protease, a class of lysosomal cathepsins that are essential effectors of autophagy and lysosomal protein degradation. In C. elegans, lysosomal cysteine proteases (e.g., CPL-1/cathepsin L) are required for autophagic flux and proteostasis maintenance, both of which are critical for normal lifespan. Loss of such proteases impairs the clearance of damaged proteins and organelles, accelerating aging phenotypes. The papain C-terminal domain is the hallmark of lysosomal cathepsins, placing this gene squarely in the autophagy-lysosome degradation axis. Functional activity of this protease therefore supports proteostasis and autophagic clearance, promoting longevity rather than opposing it.",
"confidence": 0.62,
"key_pathways": [
"lysosomal proteolysis / cathepsin activity",
"macroautophagy / autophagic flux",
"proteostasis maintenance"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumes that lysosomal cysteine proteases (cathepsins) are generally pro-longevity because they support autophagy and proteostasis. However, Y71H2AR.2 is actually anti-longevity, meaning its activity shortens lifespan (i.e., loss of function likely extends lifespan). This is consistent with some C. elegans cysteine proteases that, when knocked down, extend lifespan - possibly through mechanisms like reduced protein degradation that paradoxically benefits longevity, or through roles in pathways that limit lifespan. The model's mechanistic reasoning is plausible in general terms for cathepsin biology but is incorrect for this specific gene. The model was moderately confident (0.62) in the wrong direction. The mechanism class \"disabled_macroautophagy\" is also inconsistent with the model's own reasoning (which argues the gene promotes autophagy, not disables it), suggesting an internal inconsistency in the prediction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}