daf-18
C. elegans
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase daf-18
What the model saw
Gene: daf-18 Organism: Caenorhabditis elegans Known functions: Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase daf-18. phosphatase activity. phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity. protein binding. protein serine/threonine phosphatase activity. protein tyrosine phosphatase activity.
View unredacted entry
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase daf-18. phosphatase activity. phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity. protein binding. protein serine/threonine phosphatase activity. protein tyrosine phosphatase activity.
Solver output
daf-18 is the C. elegans ortholog of the tumor suppressor PTEN, a dual-specificity phosphatase that dephosphorylates phosphatidylinositol-3,4,5-trisphosphate (PIP3) back to PIP2. By reducing PIP3 levels, daf-18 antagonizes AGE-1 (PI3K) activity, thereby suppressing PDK-1 and AKT-1/AKT-2 kinase signaling. This inhibition of the insulin/IGF-1 signaling (IIS) pathway allows the FOXO transcription factor DAF-16 to translocate to the nucleus and activate longevity-promoting gene expression programs. Loss of daf-18 function leads to constitutive AKT activation, nuclear exclusion of DAF-16, and shortened lifespan, while its activity is required for the extended longevity seen in daf-2 mutants.
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 identified daf-18 as pro_longevity with high confidence (0.93). The mechanistic reasoning is excellent and accurate: daf-18 is indeed the C. elegans PTEN ortholog that dephosphorylates PIP3 to PIP2, antagonizing AGE-1/PI3K signaling, suppressing AKT-1/AKT-2, and allowing DAF-16/FOXO nuclear localization to promote longevity. The model correctly notes that loss of daf-18 shortens lifespan and that daf-18 activity is required for extended longevity in daf-2 mutants. All key pathways identified are correct and relevant.
Raw API responses
solver
{
"reasoning": "daf-18 is the C. elegans ortholog of the tumor suppressor PTEN, a dual-specificity phosphatase that dephosphorylates phosphatidylinositol-3,4,5-trisphosphate (PIP3) back to PIP2. By reducing PIP3 levels, daf-18 antagonizes AGE-1 (PI3K) activity, thereby suppressing PDK-1 and AKT-1/AKT-2 kinase signaling. This inhibition of the insulin/IGF-1 signaling (IIS) pathway allows the FOXO transcription factor DAF-16 to translocate to the nucleus and activate longevity-promoting gene expression programs. Loss of daf-18 function leads to constitutive AKT activation, nuclear exclusion of DAF-16, and shortened lifespan, while its activity is required for the extended longevity seen in daf-2 mutants.",
"confidence": 0.93,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) pathway",
"PI3K-AKT-FOXO (DAF-16) axis",
"PIP3 dephosphorylation / PTEN tumor suppressor pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified daf-18 as pro_longevity with high confidence (0.93). The mechanistic reasoning is excellent and accurate: daf-18 is indeed the C. elegans PTEN ortholog that dephosphorylates PIP3 to PIP2, antagonizing AGE-1/PI3K signaling, suppressing AKT-1/AKT-2, and allowing DAF-16/FOXO nuclear localization to promote longevity. The model correctly notes that loss of daf-18 shortens lifespan and that daf-18 activity is required for extended longevity in daf-2 mutants. All key pathways identified are correct and relevant.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}