osm-6
C. elegans
Intraflagellar transport protein 52 C-terminal domain-containing protein
What the model saw
Gene: osm-6 Organism: Caenorhabditis elegans Known functions: Intraflagellar transport protein 52 C-terminal domain-containing protein.
View unredacted entry
Intraflagellar transport protein 52 C-terminal domain-containing protein.
Solver output
osm-6 encodes an intraflagellar transport (IFT) protein (IFT52 homolog) essential for the assembly and maintenance of sensory cilia in C. elegans amphid and phasmid neurons. Functional cilia in chemosensory neurons are required for proper neuroendocrine signaling; loss of ciliary function disrupts sensory input to the DAF-2/insulin-IGF-1 pathway, reducing insulin-like peptide signaling and thereby promoting DAF-16/FOXO nuclear localization. Reduced IIS (insulin/IGF-1 signaling) is one of the most robust pro-longevity mechanisms in C. elegans, and osm-6 mutants with defective cilia are known to be long-lived through this mechanism. The IFT complex is specifically required for ciliary axoneme construction, and its loss phenocopies other cilia-defective mutants (e.g., daf-19, osm-5) that extend lifespan via dampened nutrient/insulin sensing.
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 osm-6 as pro_longevity (loss of function extends lifespan via reduced IIS), but the ground truth classifies it as anti_longevity. The model's reasoning follows a commonly cited but oversimplified narrative: that cilia-defective mutants are long-lived due to reduced insulin signaling. However, the actual experimental evidence for osm-6 is more nuanced — osm-6 mutants are not consistently long-lived, and the gene is classified as anti_longevity in GenAge, meaning its loss shortens lifespan or its presence promotes longevity. The model was fairly confident (0.72) in the wrong direction. The mechanistic reasoning about IFT → reduced IIS → DAF-16 activation is a plausible but incorrect application to this specific gene, making both the answer and the mechanism wrong.
Raw API responses
solver
{
"reasoning": "osm-6 encodes an intraflagellar transport (IFT) protein (IFT52 homolog) essential for the assembly and maintenance of sensory cilia in C. elegans amphid and phasmid neurons. Functional cilia in chemosensory neurons are required for proper neuroendocrine signaling; loss of ciliary function disrupts sensory input to the DAF-2/insulin-IGF-1 pathway, reducing insulin-like peptide signaling and thereby promoting DAF-16/FOXO nuclear localization. Reduced IIS (insulin/IGF-1 signaling) is one of the most robust pro-longevity mechanisms in C. elegans, and osm-6 mutants with defective cilia are known to be long-lived through this mechanism. The IFT complex is specifically required for ciliary axoneme construction, and its loss phenocopies other cilia-defective mutants (e.g., daf-19, osm-5) that extend lifespan via dampened nutrient/insulin sensing.",
"confidence": 0.72,
"key_pathways": [
"Intraflagellar transport (IFT) / ciliogenesis",
"DAF-2/insulin-IGF-1 signaling pathway",
"DAF-16/FOXO transcription factor activation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted osm-6 as pro_longevity (loss of function extends lifespan via reduced IIS), but the ground truth classifies it as anti_longevity. The model's reasoning follows a commonly cited but oversimplified narrative: that cilia-defective mutants are long-lived due to reduced insulin signaling. However, the actual experimental evidence for osm-6 is more nuanced — osm-6 mutants are not consistently long-lived, and the gene is classified as anti_longevity in GenAge, meaning its loss shortens lifespan or its presence promotes longevity. The model was fairly confident (0.72) in the wrong direction. The mechanistic reasoning about IFT → reduced IIS → DAF-16 activation is a plausible but incorrect application to this specific gene, making both the answer and the mechanism wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": true
}