TOM1
S. cerevisiae
E3 ubiquitin-protein ligase TOM1
What the model saw
Gene: TOM1 Organism: Saccharomyces cerevisiae Known functions: E3 ubiquitin-protein ligase TOM1. ubiquitin protein ligase activity. ubiquitin-protein transferase activity.
View unredacted entry
E3 ubiquitin-protein ligase TOM1. ubiquitin protein ligase activity. ubiquitin-protein transferase activity.
Solver output
TOM1 encodes an E3 ubiquitin-protein ligase in S. cerevisiae, responsible for ubiquitinating specific substrate proteins and targeting them for proteasomal degradation. E3 ligases are central to proteostasis maintenance by clearing misfolded, damaged, or excess proteins. In yeast, TOM1 has been shown to ubiquitinate excess histones and other substrates, preventing their toxic accumulation. Proper histone stoichiometry is critical for genomic stability and epigenetic regulation, both of which are linked to longevity. By maintaining proteostasis and preventing accumulation of proteotoxic species, TOM1's ubiquitin ligase activity is expected to support cellular health and promote 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 reasoned that TOM1's E3 ubiquitin ligase activity would support proteostasis and promote longevity, but in reality TOM1 is anti-longevity in yeast — meaning its deletion or loss extends lifespan. The model's reasoning about histone quality control and proteostasis is plausible in general terms but leads to the wrong conclusion. The model failed to consider that TOM1 may ubiquitinate substrates that are actually beneficial for longevity, or that TOM1 activity may promote aging through other mechanisms. The confidence of 0.62 is moderate but still clearly wrong.
Raw API responses
solver
{
"reasoning": "TOM1 encodes an E3 ubiquitin-protein ligase in S. cerevisiae, responsible for ubiquitinating specific substrate proteins and targeting them for proteasomal degradation. E3 ligases are central to proteostasis maintenance by clearing misfolded, damaged, or excess proteins. In yeast, TOM1 has been shown to ubiquitinate excess histones and other substrates, preventing their toxic accumulation. Proper histone stoichiometry is critical for genomic stability and epigenetic regulation, both of which are linked to longevity. By maintaining proteostasis and preventing accumulation of proteotoxic species, TOM1's ubiquitin ligase activity is expected to support cellular health and promote longevity.",
"confidence": 0.62,
"key_pathways": [
"ubiquitin-proteasome system",
"histone quality control",
"proteostasis maintenance"
],
"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 reasoned that TOM1's E3 ubiquitin ligase activity would support proteostasis and promote longevity, but in reality TOM1 is anti-longevity in yeast — meaning its deletion or loss extends lifespan. The model's reasoning about histone quality control and proteostasis is plausible in general terms but leads to the wrong conclusion. The model failed to consider that TOM1 may ubiquitinate substrates that are actually beneficial for longevity, or that TOM1 activity may promote aging through other mechanisms. The confidence of 0.62 is moderate but still clearly wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}