osm-5
C. elegans
Intraflagellar transport protein 88 homolog
What the model saw
Gene: osm-5 Organism: Caenorhabditis elegans Known functions: Intraflagellar transport protein 88 homolog. kinesin binding.
View unredacted entry
Intraflagellar transport protein 88 homolog. kinesin binding.
Solver output
OSM-5 is the C. elegans homolog of IFT88, a core component of the intraflagellar transport (IFT) complex B required for cilia assembly and maintenance. In C. elegans, functional cilia on sensory neurons (amphid and phasmid neurons) are essential for proper chemosensory signaling. Loss-of-function mutations in osm-5 disrupt cilia structure, impairing sensory neuron function and reducing the uptake of lipophilic dyes (Dil-filling defect). Critically, ciliary sensory neurons in C. elegans modulate neuroendocrine signaling—including insulin/IGF-1-like signaling (IIS) and DAF-7/TGF-β pathways—that regulate DAF-16/FOXO activity and longevity. Mutations that ablate specific sensory neurons (e.g., ASI, ASJ) or disrupt cilia extend lifespan by reducing pro-aging neuroendocrine signals, suggesting that intact cilia-dependent sensory signaling normally promotes aging. However, osm-5 loss-of-function mutants themselves are reported to have extended lifespan, indicating that the normal function of osm-5 (maintaining cilia and thus pro-aging sensory signaling) is anti-longevity in net effect—meaning osm-5's normal function opposes longevity. The kinesin-binding activity of OSM-5/IFT88 is required for anterograde IFT particle transport along the ciliary axoneme, directly enabling cilia-dependent neuroendocrine communication that shortens lifespan.
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 identified the mechanism (osm-5 loss disrupts cilia, which reduces pro-aging sensory signaling, extending lifespan) and even explicitly stated that "osm-5 loss-of-function mutants themselves are reported to have extended lifespan, indicating that the normal function of osm-5 (maintaining cilia and thus pro-aging sensory signaling) is anti-longevity in net effect." This reasoning correctly leads to the conclusion that osm-5 is anti_longevity. However, the model then contradicted itself by outputting "pro_longevity" as the final prediction. The reasoning was internally consistent and correct, but the final answer label was wrong. This is a case where the model's reasoning correctly identified the gene as anti_longevity but the final classification was flipped to pro_longevity, possibly due to confusion about the directionality of the terminology (anti_longevity gene = gene whose loss extends lifespan = gene whose normal function promotes aging).
Raw API responses
solver
{
"reasoning": "OSM-5 is the C. elegans homolog of IFT88, a core component of the intraflagellar transport (IFT) complex B required for cilia assembly and maintenance. In C. elegans, functional cilia on sensory neurons (amphid and phasmid neurons) are essential for proper chemosensory signaling. Loss-of-function mutations in osm-5 disrupt cilia structure, impairing sensory neuron function and reducing the uptake of lipophilic dyes (Dil-filling defect). Critically, ciliary sensory neurons in C. elegans modulate neuroendocrine signaling—including insulin/IGF-1-like signaling (IIS) and DAF-7/TGF-β pathways—that regulate DAF-16/FOXO activity and longevity. Mutations that ablate specific sensory neurons (e.g., ASI, ASJ) or disrupt cilia extend lifespan by reducing pro-aging neuroendocrine signals, suggesting that intact cilia-dependent sensory signaling normally promotes aging. However, osm-5 loss-of-function mutants themselves are reported to have extended lifespan, indicating that the normal function of osm-5 (maintaining cilia and thus pro-aging sensory signaling) is anti-longevity in net effect—meaning osm-5's normal function opposes longevity. The kinesin-binding activity of OSM-5/IFT88 is required for anterograde IFT particle transport along the ciliary axoneme, directly enabling cilia-dependent neuroendocrine communication that shortens lifespan.",
"confidence": 0.72,
"key_pathways": [
"Intraflagellar transport (IFT) / cilia assembly",
"Insulin/IGF-1 signaling (IIS) / DAF-16 regulation via sensory neurons",
"DAF-7/TGF-β neuroendocrine signaling"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified the mechanism (osm-5 loss disrupts cilia, which reduces pro-aging sensory signaling, extending lifespan) and even explicitly stated that \"osm-5 loss-of-function mutants themselves are reported to have extended lifespan, indicating that the normal function of osm-5 (maintaining cilia and thus pro-aging sensory signaling) is anti-longevity in net effect.\" This reasoning correctly leads to the conclusion that osm-5 is anti_longevity. However, the model then contradicted itself by outputting \"pro_longevity\" as the final prediction. The reasoning was internally consistent and correct, but the final answer label was wrong. This is a case where the model's reasoning correctly identified the gene as anti_longevity but the final classification was flipped to pro_longevity, possibly due to confusion about the directionality of the terminology (anti_longevity gene = gene whose loss extends lifespan = gene whose normal function promotes aging).",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}