atg-18
C. elegans
Autophagy-related protein 18
What the model saw
Gene: atg-18 Organism: Caenorhabditis elegans Known functions: Autophagy-related protein 18. phosphatidylinositol-3,5-bisphosphate binding. phosphatidylinositol-3-phosphate binding. phosphatidylinositol-4-phosphate binding. phosphatidylinositol-5-phosphate binding. protein-macromolecule adaptor activity.
View unredacted entry
Autophagy-related protein 18. phosphatidylinositol-3,5-bisphosphate binding. phosphatidylinositol-3-phosphate binding. phosphatidylinositol-4-phosphate binding. phosphatidylinositol-5-phosphate binding. protein-macromolecule adaptor activity.
Solver output
ATG-18 is a WIPI (WD repeat protein interacting with phosphoinositides) family protein that is an essential component of the autophagy machinery in C. elegans. Its binding to phosphatidylinositol-3-phosphate (PI3P) and phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2] recruits it to the phagophore assembly site, where it acts as a scaffold/adaptor to promote autophagosome formation. Functional autophagy via ATG-18 is required for lifespan extension in multiple longevity pathways in C. elegans, including daf-2/insulin signaling mutants, dietary restriction, and germline-less glp-1 mutants. Loss of atg-18 suppresses longevity in these contexts, demonstrating that its normal function is pro-longevity by enabling macroautophagy-mediated clearance of damaged proteins and organelles.
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" with high confidence (0.92), but the ground truth is "unclear." The mechanistic reasoning is scientifically sound — ATG-18/WIPI is indeed a key autophagy component, and autophagy is generally required for lifespan extension in multiple C. elegans longevity pathways. However, the GenAge database classifies atg-18's longevity influence as "unclear," suggesting the evidence is mixed or insufficient to definitively classify it as pro-longevity. The model was overconfident in its classification despite the ambiguity in the literature. The mechanism described is plausible and largely correct, but the conclusion drawn (definitively pro-longevity) does not match the curated ground truth.
Raw API responses
solver
{
"reasoning": "ATG-18 is a WIPI (WD repeat protein interacting with phosphoinositides) family protein that is an essential component of the autophagy machinery in C. elegans. Its binding to phosphatidylinositol-3-phosphate (PI3P) and phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2] recruits it to the phagophore assembly site, where it acts as a scaffold/adaptor to promote autophagosome formation. Functional autophagy via ATG-18 is required for lifespan extension in multiple longevity pathways in C. elegans, including daf-2/insulin signaling mutants, dietary restriction, and germline-less glp-1 mutants. Loss of atg-18 suppresses longevity in these contexts, demonstrating that its normal function is pro-longevity by enabling macroautophagy-mediated clearance of damaged proteins and organelles.",
"confidence": 0.92,
"key_pathways": [
"macroautophagy / autophagosome biogenesis",
"PI3P/PI(3,5)P2 phosphoinositide signaling",
"daf-2/insulin-IGF-1 longevity pathway"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" with high confidence (0.92), but the ground truth is \"unclear.\" The mechanistic reasoning is scientifically sound — ATG-18/WIPI is indeed a key autophagy component, and autophagy is generally required for lifespan extension in multiple C. elegans longevity pathways. However, the GenAge database classifies atg-18's longevity influence as \"unclear,\" suggesting the evidence is mixed or insufficient to definitively classify it as pro-longevity. The model was overconfident in its classification despite the ambiguity in the literature. The mechanism described is plausible and largely correct, but the conclusion drawn (definitively pro-longevity) does not match the curated ground truth.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}