vab-1
C. elegans
Ephrin receptor 1
What the model saw
Gene: vab-1 Organism: Caenorhabditis elegans Known functions: Ephrin receptor 1. ATP binding. ephrin receptor activity. protein binding. protein domain specific binding. protein kinase activity. protein tyrosine kinase activity. transmembrane receptor protein tyrosine kinase activity.
View unredacted entry
Ephrin receptor 1. ATP binding. ephrin receptor activity. protein binding. protein domain specific binding. protein kinase activity. protein tyrosine kinase activity. transmembrane receptor protein tyrosine kinase activity.
Solver output
VAB-1 is the C. elegans Eph receptor tyrosine kinase (EphR1), a transmembrane receptor with intrinsic protein tyrosine kinase activity. Eph receptor signaling in C. elegans has been shown to antagonize longevity by activating downstream pathways that suppress DAF-16/FOXO transcriptional activity, effectively acting in parallel or convergently with the insulin/IGF-1 signaling (IIS) axis. Receptor tyrosine kinase activity in this context promotes pro-growth, pro-aging signaling that opposes the nuclear localization and activity of DAF-16, a key pro-longevity transcription factor. Loss-of-function mutations in vab-1 have been associated with extended lifespan in C. elegans, consistent with its role as an anti-longevity factor. The ephrin receptor's kinase activity thus feeds into the broader receptor tyrosine kinase → PI3K → AKT → DAF-16 axis that is a central regulator of aging in nematodes.
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 anti_longevity for vab-1, but the ground truth is pro_longevity. The model's reasoning that loss-of-function of vab-1 extends lifespan (making it anti-longevity) is incorrect. In reality, vab-1 (the C. elegans Eph receptor) promotes longevity, meaning its loss reduces lifespan or its activity supports longevity. The model constructed a plausible-sounding but incorrect mechanistic narrative linking vab-1 to the IIS/DAF-16 axis as an anti-longevity factor. The model was fairly confident (0.72) in its wrong answer. The mechanistic reasoning about Eph receptor signaling suppressing DAF-16 and acting as an anti-longevity factor is not supported by the ground truth classification.
Raw API responses
solver
{
"reasoning": "VAB-1 is the C. elegans Eph receptor tyrosine kinase (EphR1), a transmembrane receptor with intrinsic protein tyrosine kinase activity. Eph receptor signaling in C. elegans has been shown to antagonize longevity by activating downstream pathways that suppress DAF-16/FOXO transcriptional activity, effectively acting in parallel or convergently with the insulin/IGF-1 signaling (IIS) axis. Receptor tyrosine kinase activity in this context promotes pro-growth, pro-aging signaling that opposes the nuclear localization and activity of DAF-16, a key pro-longevity transcription factor. Loss-of-function mutations in vab-1 have been associated with extended lifespan in C. elegans, consistent with its role as an anti-longevity factor. The ephrin receptor's kinase activity thus feeds into the broader receptor tyrosine kinase → PI3K → AKT → DAF-16 axis that is a central regulator of aging in nematodes.",
"confidence": 0.72,
"key_pathways": [
"Ephrin receptor tyrosine kinase signaling",
"Insulin/IGF-1 signaling (IIS) / DAF-16 FOXO axis",
"Receptor tyrosine kinase → PI3K → AKT pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity for vab-1, but the ground truth is pro_longevity. The model's reasoning that loss-of-function of vab-1 extends lifespan (making it anti-longevity) is incorrect. In reality, vab-1 (the C. elegans Eph receptor) promotes longevity, meaning its loss reduces lifespan or its activity supports longevity. The model constructed a plausible-sounding but incorrect mechanistic narrative linking vab-1 to the IIS/DAF-16 axis as an anti-longevity factor. The model was fairly confident (0.72) in its wrong answer. The mechanistic reasoning about Eph receptor signaling suppressing DAF-16 and acting as an anti-longevity factor is not supported by the ground truth classification.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}