rab-10
C. elegans
Ras-related protein Rab-10
What the model saw
Gene: rab-10 Organism: Caenorhabditis elegans Known functions: Ras-related protein Rab-10. G protein activity. GTP binding. GTPase activating protein binding. GTPase activity. ankyrin repeat binding. myosin V binding. protein binding.
View unredacted entry
Ras-related protein Rab-10. G protein activity. GTP binding. GTPase activating protein binding. GTPase activity. ankyrin repeat binding. myosin V binding. protein binding.
Solver output
RAB-10 is a Rab GTPase that cycles between GTP- and GDP-bound states to regulate vesicular trafficking, particularly in recycling endosome pathways and basolateral membrane trafficking. In C. elegans, RAB-10 has been shown to mediate insulin/IGF-1 receptor (DAF-2) trafficking and recycling at the plasma membrane; loss of rab-10 reduces surface DAF-2 levels, thereby dampening PI3K-AKT signaling and promoting nuclear localization of the FOXO transcription factor DAF-16, which extends lifespan. By facilitating DAF-2 receptor recycling, RAB-10 normally sustains pro-aging insulin/IGF-1 signaling, meaning its normal function is anti-longevity in effect — however, the gene's role in maintaining proper vesicular trafficking and intercellular communication is broadly important. The myosin V binding and ankyrin repeat binding activities support its role in cytoskeletal-dependent vesicle transport. Because RAB-10's primary documented role in aging contexts is sustaining DAF-2/insulin receptor surface availability and thus suppressing DAF-16/FOXO, its normal function opposes longevity by promoting the pro-aging insulin signaling axis.
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." Interestingly, the model's reasoning actually arrives at the correct mechanistic conclusion (RAB-10 sustains pro-aging insulin signaling, so its normal function opposes longevity = anti_longevity), but then contradicts itself by outputting "pro_longevity" as the final answer. The reasoning explicitly states "its normal function opposes longevity by promoting the pro-aging insulin signaling axis," which aligns with anti_longevity, yet the model selected the wrong label. This is a case of internally inconsistent reasoning leading to a wrong final answer. The mechanism described (DAF-2 receptor recycling via RAB-10) is plausible but not well-established in the literature as the primary aging mechanism for rab-10 in C. elegans. The model appears confused between the effect of the gene's activity (anti-longevity) and the effect of its loss-of-function (pro-longevity), ultimately selecting the wrong category despite partially correct reasoning.
Raw API responses
solver
{
"reasoning": "RAB-10 is a Rab GTPase that cycles between GTP- and GDP-bound states to regulate vesicular trafficking, particularly in recycling endosome pathways and basolateral membrane trafficking. In C. elegans, RAB-10 has been shown to mediate insulin/IGF-1 receptor (DAF-2) trafficking and recycling at the plasma membrane; loss of rab-10 reduces surface DAF-2 levels, thereby dampening PI3K-AKT signaling and promoting nuclear localization of the FOXO transcription factor DAF-16, which extends lifespan. By facilitating DAF-2 receptor recycling, RAB-10 normally sustains pro-aging insulin/IGF-1 signaling, meaning its normal function is anti-longevity in effect — however, the gene's role in maintaining proper vesicular trafficking and intercellular communication is broadly important. The myosin V binding and ankyrin repeat binding activities support its role in cytoskeletal-dependent vesicle transport. Because RAB-10's primary documented role in aging contexts is sustaining DAF-2/insulin receptor surface availability and thus suppressing DAF-16/FOXO, its normal function opposes longevity by promoting the pro-aging insulin signaling axis.",
"confidence": 0.62,
"key_pathways": [
"Insulin/IGF-1 signaling (DAF-2 receptor recycling)",
"Rab GTPase vesicular trafficking / recycling endosome pathway",
"DAF-16/FOXO transcription factor regulation"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" Interestingly, the model's reasoning actually arrives at the correct mechanistic conclusion (RAB-10 sustains pro-aging insulin signaling, so its normal function opposes longevity = anti_longevity), but then contradicts itself by outputting \"pro_longevity\" as the final answer. The reasoning explicitly states \"its normal function opposes longevity by promoting the pro-aging insulin signaling axis,\" which aligns with anti_longevity, yet the model selected the wrong label. This is a case of internally inconsistent reasoning leading to a wrong final answer. The mechanism described (DAF-2 receptor recycling via RAB-10) is plausible but not well-established in the literature as the primary aging mechanism for rab-10 in C. elegans. The model appears confused between the effect of the gene's activity (anti-longevity) and the effect of its loss-of-function (pro-longevity), ultimately selecting the wrong category despite partially correct reasoning.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}