Orco
D. melanogaster
Odorant receptor co-receptor
What the model saw
Gene: Orco Organism: Drosophila melanogaster Known functions: Odorant receptor co-receptor. odorant receptor co-receptor. calmodulin binding. coreceptor activity. intracellularly gated calcium channel activity. ionotropic olfactory receptor activity. odorant binding. olfactory receptor activity. protein binding. protein homodimerization activity.
View unredacted entry
Odorant receptor co-receptor. odorant receptor co-receptor. calmodulin binding. coreceptor activity. intracellularly gated calcium channel activity. ionotropic olfactory receptor activity. odorant binding. olfactory receptor activity. protein binding. protein homodimerization activity.
Solver output
Orco is the obligate co-receptor for all odorant receptors in Drosophila, forming heteromeric ionotropic receptor complexes that gate calcium influx in olfactory sensory neurons. Olfactory signaling in Drosophila is a key modality for detecting food-derived volatile cues (e.g., diacetyl, isoamyl acetate) that activate nutrient-sensing and neuroendocrine pathways. Loss of olfactory input via Orco disruption has been shown to extend lifespan in Drosophila, partly by mimicking dietary restriction signals through reduced insulin/IGF-1 signaling (IIS) — olfactory perception of food odors promotes IIS activity, which is anti-longevity. Orco's calmodulin-binding activity links olfactory calcium signaling to downstream neuromodulatory cascades that regulate systemic metabolic state. Thus, normal Orco function, by enabling food-odor detection and stimulating IIS, opposes longevity; however, since the question asks about the gene's normal function promoting or opposing longevity, Orco's activity is net anti-longevity (its presence shortens life relative to its absence). Nonetheless, framing it as "pro-longevity" would be incorrect — Orco's normal function promotes aging-accelerating neuroendocrine signaling.
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's reasoning is actually correct - it correctly identifies that Orco's normal function promotes aging-accelerating neuroendocrine signaling (via IIS), making it anti-longevity. The model even explicitly states "Orco's activity is net anti-longevity" and "Orco's normal function promotes aging-accelerating neuroendocrine signaling." However, the model then contradicts itself by outputting "pro_longevity" as the final prediction. This is a self-contradictory answer where the reasoning leads to the correct conclusion (anti_longevity) but the final label is wrong (pro_longevity). The model appears confused about the directionality convention - it seems to have mixed up whether the question asks about the gene's effect when present (anti_longevity) vs. when absent (pro_longevity for lifespan). The mechanism understanding is correct but the final answer is wrong.
Raw API responses
solver
{
"reasoning": "Orco is the obligate co-receptor for all odorant receptors in Drosophila, forming heteromeric ionotropic receptor complexes that gate calcium influx in olfactory sensory neurons. Olfactory signaling in Drosophila is a key modality for detecting food-derived volatile cues (e.g., diacetyl, isoamyl acetate) that activate nutrient-sensing and neuroendocrine pathways. Loss of olfactory input via Orco disruption has been shown to extend lifespan in Drosophila, partly by mimicking dietary restriction signals through reduced insulin/IGF-1 signaling (IIS) — olfactory perception of food odors promotes IIS activity, which is anti-longevity. Orco's calmodulin-binding activity links olfactory calcium signaling to downstream neuromodulatory cascades that regulate systemic metabolic state. Thus, normal Orco function, by enabling food-odor detection and stimulating IIS, opposes longevity; however, since the question asks about the gene's normal function promoting or opposing longevity, Orco's activity is net anti-longevity (its presence shortens life relative to its absence). Nonetheless, framing it as \"pro-longevity\" would be incorrect — Orco's normal function promotes aging-accelerating neuroendocrine signaling.",
"confidence": 0.62,
"key_pathways": [
"olfactory receptor signaling / ionotropic calcium channel gating",
"insulin/IGF-1 signaling (IIS) modulation via olfactory neuroendocrine axis",
"altered intercellular communication via sensory neuron-to-systemic signaling"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model's reasoning is actually correct - it correctly identifies that Orco's normal function promotes aging-accelerating neuroendocrine signaling (via IIS), making it anti-longevity. The model even explicitly states \"Orco's activity is net anti-longevity\" and \"Orco's normal function promotes aging-accelerating neuroendocrine signaling.\" However, the model then contradicts itself by outputting \"pro_longevity\" as the final prediction. This is a self-contradictory answer where the reasoning leads to the correct conclusion (anti_longevity) but the final label is wrong (pro_longevity). The model appears confused about the directionality convention - it seems to have mixed up whether the question asks about the gene's effect when present (anti_longevity) vs. when absent (pro_longevity for lifespan). The mechanism understanding is correct but the final answer is wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 2,
"ground_truth_questionable": false
}