IPK1
S. cerevisiae
inositol pentakisphosphate 2-kinase
What the model saw
Gene: IPK1 Organism: Saccharomyces cerevisiae Known functions: inositol pentakisphosphate 2-kinase. ATP binding. inositol-1,3,4,5,6-pentakisphosphate 2-kinase activity.
View unredacted entry
inositol pentakisphosphate 2-kinase. ATP binding. inositol-1,3,4,5,6-pentakisphosphate 2-kinase activity.
Solver output
IPK1 encodes inositol-1,3,4,5,6-pentakisphosphate 2-kinase, which catalyzes the final step in the synthesis of inositol hexakisphosphate (IP6) from IP5. IP6 and its downstream product IP7 (inositol pyrophosphate) are critical regulators of the Akt/PKB signaling pathway — IP7 directly inhibits Akt by competing with PIP3 for the pleckstrin homology domain, thereby attenuating insulin/IGF-1-like nutrient sensing signaling. In yeast, reduced Akt/TORC1 signaling is a well-established pro-longevity mechanism. By producing IP6 (the precursor to IP7), IPK1 activity supports the inositol pyrophosphate axis that dampens nutrient-sensing kinase activity. Additionally, IP6 plays roles in mRNA export and genome stability, which are ancillary pro-longevity functions. Loss of IPK1 would reduce IP6/IP7 levels, potentially derepressing nutrient-sensing pathways and shortening lifespan.
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. IPK1 is anti-longevity, meaning its deletion extends lifespan (or its presence shortens it). The model's reasoning about IP6/IP7 inhibiting Akt/PKB and thereby dampening nutrient sensing is plausible in principle, but it leads to the wrong conclusion. The model argues that IPK1 produces IP6 which leads to IP7 which inhibits Akt, making IPK1 pro-longevity. However, the actual experimental data shows IPK1 is anti-longevity in yeast. The mechanistic reasoning, while creative, is incorrect in its final conclusion and likely misapplies mammalian Akt/PH domain biology to yeast. The model had low-moderate confidence (0.55) but still got both the answer and the mechanism wrong.
Raw API responses
solver
{
"reasoning": "IPK1 encodes inositol-1,3,4,5,6-pentakisphosphate 2-kinase, which catalyzes the final step in the synthesis of inositol hexakisphosphate (IP6) from IP5. IP6 and its downstream product IP7 (inositol pyrophosphate) are critical regulators of the Akt/PKB signaling pathway — IP7 directly inhibits Akt by competing with PIP3 for the pleckstrin homology domain, thereby attenuating insulin/IGF-1-like nutrient sensing signaling. In yeast, reduced Akt/TORC1 signaling is a well-established pro-longevity mechanism. By producing IP6 (the precursor to IP7), IPK1 activity supports the inositol pyrophosphate axis that dampens nutrient-sensing kinase activity. Additionally, IP6 plays roles in mRNA export and genome stability, which are ancillary pro-longevity functions. Loss of IPK1 would reduce IP6/IP7 levels, potentially derepressing nutrient-sensing pathways and shortening lifespan.",
"confidence": 0.55,
"key_pathways": [
"inositol polyphosphate / IP6-IP7 synthesis",
"Akt/PKB nutrient sensing inhibition via inositol pyrophosphates",
"TOR signaling attenuation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. IPK1 is anti-longevity, meaning its deletion extends lifespan (or its presence shortens it). The model's reasoning about IP6/IP7 inhibiting Akt/PKB and thereby dampening nutrient sensing is plausible in principle, but it leads to the wrong conclusion. The model argues that IPK1 produces IP6 which leads to IP7 which inhibits Akt, making IPK1 pro-longevity. However, the actual experimental data shows IPK1 is anti-longevity in yeast. The mechanistic reasoning, while creative, is incorrect in its final conclusion and likely misapplies mammalian Akt/PH domain biology to yeast. The model had low-moderate confidence (0.55) but still got both the answer and the mechanism wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}