egl-8
C. elegans
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase;1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta egl-8;Phosphoinositide phospholipase C
What the model saw
Gene: egl-8 Organism: Caenorhabditis elegans Known functions: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase;1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta egl-8;Phosphoinositide phospholipase C. calcium ion binding. phosphatidylinositol-4,5-bisphosphate phospholipase C activity. phosphoric diester hydrolase activity.
View unredacted entry
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase;1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta egl-8;Phosphoinositide phospholipase C. calcium ion binding. phosphatidylinositol-4,5-bisphosphate phospholipase C activity. phosphoric diester hydrolase activity.
Solver output
EGL-8 is the C. elegans phospholipase C-beta (PLCβ), which hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP2) to generate diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP3). DAG activates protein kinase C (PKC), while IP3 triggers intracellular calcium release. In C. elegans, this PLCβ signaling axis operates downstream of Gαq (EGL-30), a pathway known to antagonize longevity by promoting neuronal activity and counteracting the pro-longevity effects of reduced insulin/IGF-1 signaling and DAF-16/FOXO. Elevated Gαq-PLCβ-DAG signaling shortens lifespan, while loss-of-function in this pathway (including egl-8 mutants) extends lifespan, placing EGL-8's normal function in opposition to longevity. The calcium-dependent signaling downstream of EGL-8 also intersects with mitochondrial and metabolic regulation in ways that tend to promote aging rather than oppose it.
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 egl-8 as anti_longevity. The mechanistic reasoning is accurate and well-detailed: EGL-8 is PLCβ acting downstream of Gαq (EGL-30), generating DAG and IP3, promoting neuronal activity and opposing pro-longevity pathways. Loss-of-function of egl-8 extends lifespan in C. elegans, making it anti-longevity in its normal function. The mechanism class "deregulated_nutrient_sensing" is a slight oversimplification (it's more of a neuromodulatory/Gαq signaling pathway), but the detailed reasoning correctly identifies the actual pathway. Confidence of 0.68 is appropriately calibrated.
Raw API responses
solver
{
"reasoning": "EGL-8 is the C. elegans phospholipase C-beta (PLCβ), which hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP2) to generate diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP3). DAG activates protein kinase C (PKC), while IP3 triggers intracellular calcium release. In C. elegans, this PLCβ signaling axis operates downstream of Gαq (EGL-30), a pathway known to antagonize longevity by promoting neuronal activity and counteracting the pro-longevity effects of reduced insulin/IGF-1 signaling and DAF-16/FOXO. Elevated Gαq-PLCβ-DAG signaling shortens lifespan, while loss-of-function in this pathway (including egl-8 mutants) extends lifespan, placing EGL-8's normal function in opposition to longevity. The calcium-dependent signaling downstream of EGL-8 also intersects with mitochondrial and metabolic regulation in ways that tend to promote aging rather than oppose it.",
"confidence": 0.68,
"key_pathways": [
"Gαq-PLCβ (EGL-30/EGL-8) signaling",
"DAG/PKC signaling",
"IP3-mediated calcium release"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted egl-8 as anti_longevity. The mechanistic reasoning is accurate and well-detailed: EGL-8 is PLCβ acting downstream of Gαq (EGL-30), generating DAG and IP3, promoting neuronal activity and opposing pro-longevity pathways. Loss-of-function of egl-8 extends lifespan in C. elegans, making it anti-longevity in its normal function. The mechanism class \"deregulated_nutrient_sensing\" is a slight oversimplification (it's more of a neuromodulatory/Gαq signaling pathway), but the detailed reasoning correctly identifies the actual pathway. Confidence of 0.68 is appropriately calibrated.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}