unc-31
C. elegans
Calcium-dependent secretion activator
What the model saw
Gene: unc-31 Organism: Caenorhabditis elegans Known functions: Calcium-dependent secretion activator. calcium ion binding. phosphatidylinositol-4,5-bisphosphate binding.
View unredacted entry
Calcium-dependent secretion activator. calcium ion binding. phosphatidylinositol-4,5-bisphosphate binding.
Solver output
UNC-31 is the C. elegans ortholog of CAPS (Calcium-dependent Activator Protein for Secretion), which primes dense-core vesicles (DCVs) for calcium-triggered exocytosis. In C. elegans, UNC-31/CAPS is required for the secretion of neuropeptides and insulin-like peptides (ILPs) from neurons and other tissues. Several ILPs secreted via this pathway (e.g., DAF-28, INS-7) act as agonists of the DAF-2/insulin-IGF-1 receptor, thereby activating the PI3K-AKT axis and suppressing the FOXO transcription factor DAF-16. Loss of unc-31 reduces ILP secretion, which phenocopies reduced insulin/IGF-1 signaling and leads to DAF-16 nuclear localization and extended lifespan. Its PIP2-binding activity further supports membrane docking of DCVs, reinforcing its role in promoting pro-aging insulin-like signaling. Thus, normal UNC-31 function sustains a secretory tone that drives DAF-2 activation and opposes longevity.
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 unc-31. The mechanistic reasoning is excellent and well-supported: UNC-31/CAPS promotes dense-core vesicle exocytosis of insulin-like peptides (ILPs) that activate DAF-2/insulin-IGF-1 signaling, suppressing DAF-16/FOXO. Loss of unc-31 reduces ILP secretion, phenocopying reduced insulin signaling and extending lifespan. The model correctly identifies the key pathway (insulin/IGF-1 signaling via DAF-2/DAF-16), the molecular mechanism (DCV exocytosis, neuropeptide secretion), and the calcium/PIP2 binding functions. The confidence of 0.68 is appropriately calibrated given the complexity of the pathway.
Raw API responses
solver
{
"reasoning": "UNC-31 is the C. elegans ortholog of CAPS (Calcium-dependent Activator Protein for Secretion), which primes dense-core vesicles (DCVs) for calcium-triggered exocytosis. In C. elegans, UNC-31/CAPS is required for the secretion of neuropeptides and insulin-like peptides (ILPs) from neurons and other tissues. Several ILPs secreted via this pathway (e.g., DAF-28, INS-7) act as agonists of the DAF-2/insulin-IGF-1 receptor, thereby activating the PI3K-AKT axis and suppressing the FOXO transcription factor DAF-16. Loss of unc-31 reduces ILP secretion, which phenocopies reduced insulin/IGF-1 signaling and leads to DAF-16 nuclear localization and extended lifespan. Its PIP2-binding activity further supports membrane docking of DCVs, reinforcing its role in promoting pro-aging insulin-like signaling. Thus, normal UNC-31 function sustains a secretory tone that drives DAF-2 activation and opposes longevity.",
"confidence": 0.68,
"key_pathways": [
"insulin/IGF-1 signaling (DAF-2/DAF-16 axis)",
"dense-core vesicle exocytosis / neuropeptide secretion",
"calcium-dependent secretion activation"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for unc-31. The mechanistic reasoning is excellent and well-supported: UNC-31/CAPS promotes dense-core vesicle exocytosis of insulin-like peptides (ILPs) that activate DAF-2/insulin-IGF-1 signaling, suppressing DAF-16/FOXO. Loss of unc-31 reduces ILP secretion, phenocopying reduced insulin signaling and extending lifespan. The model correctly identifies the key pathway (insulin/IGF-1 signaling via DAF-2/DAF-16), the molecular mechanism (DCV exocytosis, neuropeptide secretion), and the calcium/PIP2 binding functions. The confidence of 0.68 is appropriately calibrated given the complexity of the pathway.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}