loco
D. melanogaster
locomotion defects
What the model saw
Gene: loco Organism: Drosophila melanogaster Known functions: locomotion defects. G-protein alpha-subunit binding. GDP-dissociation inhibitor activity. GTPase activator activity. GTPase regulator activity. protein binding.
View unredacted entry
locomotion defects. G-protein alpha-subunit binding. GDP-dissociation inhibitor activity. GTPase activator activity. GTPase regulator activity. protein binding.
Solver output
The loco (locomotion defects) gene encodes a RGS (Regulator of G-protein Signaling) domain protein in Drosophila that acts as a GTPase-activating protein (GAP) for Gα subunits, accelerating GTP hydrolysis and thereby attenuating G-protein coupled receptor (GPCR) signaling. By functioning as a GDP-dissociation inhibitor and GTPase activator for Gαi, loco negatively regulates G-protein signaling cascades that feed into nutrient-sensing and growth pathways, including those linked to insulin/IGF-like signaling (IIS). Dampening Gαi-coupled GPCR signaling through loco's GAP activity would be expected to reduce downstream PI3K/Akt/TOR pathway activation, mimicking the pro-longevity effects of reduced IIS. Loss of loco in Drosophila leads to hyperactivated G-protein signaling and is associated with neurological and metabolic defects, consistent with dysregulated nutrient sensing. Thus, the normal function of loco—restraining Gα-mediated signaling—aligns with pro-longevity mechanisms that reduce anabolic/growth 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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about loco's RGS/GAP activity is mechanistically plausible in isolation, but it drew the wrong conclusion about the direction of longevity influence. The model speculated that loco's dampening of G-protein signaling would reduce IIS/TOR pathway activation and thus extend lifespan, but the actual GenAge classification is anti_longevity, meaning loco normally promotes longevity loss (i.e., its loss or reduction extends lifespan, or its presence shortens it). The model's mechanistic framing—connecting Gαi GAP activity to reduced IIS—is speculative and not well-supported, and the final prediction is incorrect. Confidence of 0.62 is moderate but still wrong.
Raw API responses
solver
{
"reasoning": "The loco (locomotion defects) gene encodes a RGS (Regulator of G-protein Signaling) domain protein in Drosophila that acts as a GTPase-activating protein (GAP) for Gα subunits, accelerating GTP hydrolysis and thereby attenuating G-protein coupled receptor (GPCR) signaling. By functioning as a GDP-dissociation inhibitor and GTPase activator for Gαi, loco negatively regulates G-protein signaling cascades that feed into nutrient-sensing and growth pathways, including those linked to insulin/IGF-like signaling (IIS). Dampening Gαi-coupled GPCR signaling through loco's GAP activity would be expected to reduce downstream PI3K/Akt/TOR pathway activation, mimicking the pro-longevity effects of reduced IIS. Loss of loco in Drosophila leads to hyperactivated G-protein signaling and is associated with neurological and metabolic defects, consistent with dysregulated nutrient sensing. Thus, the normal function of loco—restraining Gα-mediated signaling—aligns with pro-longevity mechanisms that reduce anabolic/growth signaling.",
"confidence": 0.62,
"key_pathways": [
"G-protein signaling (Gαi GAP activity)",
"Insulin/IGF-like signaling (IIS) pathway modulation",
"GPCR-coupled nutrient sensing"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about loco's RGS/GAP activity is mechanistically plausible in isolation, but it drew the wrong conclusion about the direction of longevity influence. The model speculated that loco's dampening of G-protein signaling would reduce IIS/TOR pathway activation and thus extend lifespan, but the actual GenAge classification is anti_longevity, meaning loco normally promotes longevity loss (i.e., its loss or reduction extends lifespan, or its presence shortens it). The model's mechanistic framing—connecting Gαi GAP activity to reduced IIS—is speculative and not well-supported, and the final prediction is incorrect. Confidence of 0.62 is moderate but still wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}