INP51
S. cerevisiae
phosphoinositide 5-phosphatase INP51
What the model saw
Gene: INP51 Organism: Saccharomyces cerevisiae Known functions: phosphoinositide 5-phosphatase INP51. inositol-1,4,5-trisphosphate 5-phosphatase activity. phosphatase activity. phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity. phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. protein binding.
View unredacted entry
phosphoinositide 5-phosphatase INP51. inositol-1,4,5-trisphosphate 5-phosphatase activity. phosphatase activity. phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity. phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. protein binding.
Solver output
INP51 encodes a phosphoinositide 5-phosphatase that dephosphorylates PI(4,5)P2 and PI(3,5)P2, reducing cellular levels of these phosphoinositides. PI(4,5)P2 is a key upstream activator of the TORC2-Ypk1 signaling axis and also feeds into PI(3,4,5)P3-like signaling contexts; by hydrolyzing these lipid second messengers, INP51 dampens pro-survival phosphoinositide signaling. Critically, PI(3,5)P2 is required for proper vacuolar/lysosomal function and autophagy flux in yeast — its degradation by INP51 would impair autophagic recycling, a process tightly linked to longevity. Additionally, phosphoinositide signaling through PI(4,5)P2 modulates nutrient-sensing pathways including TOR and PKA; excessive 5-phosphatase activity would reduce the lipid signals that support these pathways in a balanced manner. Loss of INP51 function has been associated with extended chronological lifespan in yeast screens, consistent with the idea that its normal activity is anti-longevity by limiting beneficial phosphoinositide-dependent signaling and autophagy.
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 for INP51. The mechanistic reasoning is plausible - INP51 as a phosphoinositide 5-phosphatase that degrades PI(4,5)P2 and PI(3,5)P2, thereby limiting beneficial phosphoinositide signaling and autophagy. The model correctly notes that loss of INP51 extends chronological lifespan, making it anti-longevity. However, the reasoning is somewhat convoluted and mixes multiple pathways without strong specificity. The model's confidence of 0.65 is appropriately moderate. The core logic (INP51 deletion extends lifespan → INP51 is anti-longevity) is sound, though the detailed mechanistic explanation about TORC2-Ypk1 and PI(3,5)P2/autophagy connections is speculative and not well-established for this specific gene.
Raw API responses
solver
{
"reasoning": "INP51 encodes a phosphoinositide 5-phosphatase that dephosphorylates PI(4,5)P2 and PI(3,5)P2, reducing cellular levels of these phosphoinositides. PI(4,5)P2 is a key upstream activator of the TORC2-Ypk1 signaling axis and also feeds into PI(3,4,5)P3-like signaling contexts; by hydrolyzing these lipid second messengers, INP51 dampens pro-survival phosphoinositide signaling. Critically, PI(3,5)P2 is required for proper vacuolar/lysosomal function and autophagy flux in yeast — its degradation by INP51 would impair autophagic recycling, a process tightly linked to longevity. Additionally, phosphoinositide signaling through PI(4,5)P2 modulates nutrient-sensing pathways including TOR and PKA; excessive 5-phosphatase activity would reduce the lipid signals that support these pathways in a balanced manner. Loss of INP51 function has been associated with extended chronological lifespan in yeast screens, consistent with the idea that its normal activity is anti-longevity by limiting beneficial phosphoinositide-dependent signaling and autophagy.",
"confidence": 0.65,
"key_pathways": [
"PI(4,5)P2/PI(3,5)P2 phosphoinositide signaling",
"TORC2-Ypk1 nutrient sensing",
"vacuolar autophagy flux (PI(3,5)P2-dependent)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for INP51. The mechanistic reasoning is plausible - INP51 as a phosphoinositide 5-phosphatase that degrades PI(4,5)P2 and PI(3,5)P2, thereby limiting beneficial phosphoinositide signaling and autophagy. The model correctly notes that loss of INP51 extends chronological lifespan, making it anti-longevity. However, the reasoning is somewhat convoluted and mixes multiple pathways without strong specificity. The model's confidence of 0.65 is appropriately moderate. The core logic (INP51 deletion extends lifespan → INP51 is anti-longevity) is sound, though the detailed mechanistic explanation about TORC2-Ypk1 and PI(3,5)P2/autophagy connections is speculative and not well-established for this specific gene.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}