SNX3
S. cerevisiae
Snx3p
What the model saw
Gene: SNX3 Organism: Saccharomyces cerevisiae Known functions: Snx3p. phosphatidylinositol binding. phosphatidylinositol-3-phosphate binding.
View unredacted entry
Snx3p. phosphatidylinositol binding. phosphatidylinositol-3-phosphate binding.
Solver output
SNX3 (Snx3p) is a sorting nexin that binds phosphatidylinositol-3-phosphate (PI3P) via its PX domain, a lipid species generated by the Vps34 PI3-kinase complex on endosomal and autophagosomal membranes. PI3P binding by sorting nexins is essential for proper endosomal cargo sorting and retromer-mediated retrograde trafficking, which supports vacuolar/lysosomal function. In yeast, intact vacuolar function and endosomal trafficking are critical for autophagy flux and proteostasis. Loss of SNX3 function impairs retromer-dependent recycling and vacuolar homeostasis, which would compromise autophagic degradation capacity—a key pro-longevity pathway. Thus, the normal function of SNX3 in PI3P-dependent endosomal sorting supports macroautophagy and vacuolar integrity, promoting 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. SNX3 is anti-longevity in yeast, meaning its deletion extends lifespan rather than shortening it. The model's reasoning assumed that SNX3's role in PI3P-dependent endosomal sorting and retromer trafficking would support autophagy and vacuolar homeostasis, making it pro-longevity. However, the actual finding is the opposite — loss of SNX3 extends lifespan, making it anti-longevity. The mechanistic reasoning about retromer and autophagy support is plausible in general terms but leads to the wrong conclusion for this specific gene. The model had moderate confidence (0.62) but was still clearly wrong on both the answer and the mechanistic interpretation as applied to this gene.
Raw API responses
solver
{
"reasoning": "SNX3 (Snx3p) is a sorting nexin that binds phosphatidylinositol-3-phosphate (PI3P) via its PX domain, a lipid species generated by the Vps34 PI3-kinase complex on endosomal and autophagosomal membranes. PI3P binding by sorting nexins is essential for proper endosomal cargo sorting and retromer-mediated retrograde trafficking, which supports vacuolar/lysosomal function. In yeast, intact vacuolar function and endosomal trafficking are critical for autophagy flux and proteostasis. Loss of SNX3 function impairs retromer-dependent recycling and vacuolar homeostasis, which would compromise autophagic degradation capacity—a key pro-longevity pathway. Thus, the normal function of SNX3 in PI3P-dependent endosomal sorting supports macroautophagy and vacuolar integrity, promoting longevity.",
"confidence": 0.62,
"key_pathways": [
"PI3P-dependent endosomal sorting",
"retromer-mediated retrograde trafficking",
"vacuolar/lysosomal homeostasis and autophagy"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. SNX3 is anti-longevity in yeast, meaning its deletion extends lifespan rather than shortening it. The model's reasoning assumed that SNX3's role in PI3P-dependent endosomal sorting and retromer trafficking would support autophagy and vacuolar homeostasis, making it pro-longevity. However, the actual finding is the opposite — loss of SNX3 extends lifespan, making it anti-longevity. The mechanistic reasoning about retromer and autophagy support is plausible in general terms but leads to the wrong conclusion for this specific gene. The model had moderate confidence (0.62) but was still clearly wrong on both the answer and the mechanistic interpretation as applied to this gene.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}