SNA3
S. cerevisiae
Sna3p
What the model saw
Gene: SNA3 Organism: Saccharomyces cerevisiae Known functions: Sna3p. protein binding. ubiquitin protein ligase binding.
View unredacted entry
Sna3p. protein binding. ubiquitin protein ligase binding.
Solver output
SNA3 encodes a small integral membrane protein (Sna3p) that functions as a ubiquitin ligase-binding adaptor, specifically interacting with the HECT-domain E3 ligase Rsp5. Sna3p is known to be sorted into multivesicular bodies (MVBs) via ubiquitin-dependent endosomal sorting (ESCRT pathway), and its binding to Rsp5 facilitates its own ubiquitination and cargo sorting. Dysregulation of ubiquitin-mediated protein quality control and endosomal trafficking can impair proteostasis and promote accumulation of damaged or misfolded proteins. Because Sna3p acts as a substrate/adaptor that engages the ubiquitin ligase machinery for its own degradative sorting rather than promoting proteostasis broadly, its normal function does not directly extend lifespan; instead, overactive or aberrant ubiquitin ligase engagement through Sna3p could titrate Rsp5 away from other pro-longevity substrates, potentially reducing replicative or chronological lifespan. The net effect is a modest anti-longevity prediction, though the evidence is indirect.
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 correctly predicted anti_longevity, matching the ground truth. However, the mechanistic reasoning is speculative and indirect. The model's explanation centers on Sna3p potentially "titrating" Rsp5 away from pro-longevity substrates, which is a hypothetical mechanism not well-supported by direct evidence. The actual anti-longevity effect of SNA3 in yeast is typically demonstrated through deletion studies showing extended lifespan when SNA3 is removed, but the model doesn't clearly articulate this. The mechanism_class of "cellular_senescence" is also questionable for a yeast gene - yeast doesn't undergo classical cellular senescence. The reasoning is largely speculative and indirect, and the confidence is appropriately low (0.52), suggesting the model was essentially guessing. The correct answer appears to have been reached more by process of elimination or general reasoning about ubiquitin pathway components rather than specific knowledge of SNA3's role in longevity.
Raw API responses
solver
{
"reasoning": "SNA3 encodes a small integral membrane protein (Sna3p) that functions as a ubiquitin ligase-binding adaptor, specifically interacting with the HECT-domain E3 ligase Rsp5. Sna3p is known to be sorted into multivesicular bodies (MVBs) via ubiquitin-dependent endosomal sorting (ESCRT pathway), and its binding to Rsp5 facilitates its own ubiquitination and cargo sorting. Dysregulation of ubiquitin-mediated protein quality control and endosomal trafficking can impair proteostasis and promote accumulation of damaged or misfolded proteins. Because Sna3p acts as a substrate/adaptor that engages the ubiquitin ligase machinery for its own degradative sorting rather than promoting proteostasis broadly, its normal function does not directly extend lifespan; instead, overactive or aberrant ubiquitin ligase engagement through Sna3p could titrate Rsp5 away from other pro-longevity substrates, potentially reducing replicative or chronological lifespan. The net effect is a modest anti-longevity prediction, though the evidence is indirect.",
"confidence": 0.52,
"key_pathways": [
"Rsp5/HECT E3 ubiquitin ligase pathway",
"ESCRT/multivesicular body sorting",
"ubiquitin-mediated protein quality control"
],
"mechanism_class": "cellular_senescence",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity, matching the ground truth. However, the mechanistic reasoning is speculative and indirect. The model's explanation centers on Sna3p potentially \"titrating\" Rsp5 away from pro-longevity substrates, which is a hypothetical mechanism not well-supported by direct evidence. The actual anti-longevity effect of SNA3 in yeast is typically demonstrated through deletion studies showing extended lifespan when SNA3 is removed, but the model doesn't clearly articulate this. The mechanism_class of \"cellular_senescence\" is also questionable for a yeast gene - yeast doesn't undergo classical cellular senescence. The reasoning is largely speculative and indirect, and the confidence is appropriately low (0.52), suggesting the model was essentially guessing. The correct answer appears to have been reached more by process of elimination or general reasoning about ubiquitin pathway components rather than specific knowledge of SNA3's role in longevity.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}