egl-45
C. elegans
Eukaryotic translation initiation factor 3 subunit A
What the model saw
Gene: egl-45 Organism: Caenorhabditis elegans Known functions: Eukaryotic translation initiation factor 3 subunit A. RNA binding. translation initiation factor activity. translation regulator activity.
View unredacted entry
Eukaryotic translation initiation factor 3 subunit A. RNA binding. translation initiation factor activity. translation regulator activity.
Solver output
egl-45 encodes the eIF3a subunit of the eukaryotic translation initiation factor 3 complex, a central regulator of cap-dependent mRNA translation. In the context of aging, global translational activity is tightly coupled to nutrient-sensing pathways, particularly TOR (mTORC1) signaling, which phosphorylates downstream effectors to promote ribosome biogenesis and translation initiation. Reduced translation initiation—through partial loss of eIF3 subunit function or TOR inhibition—is a well-established pro-longevity intervention in C. elegans and other organisms. However, egl-45/eIF3a is an essential scaffolding subunit of the eIF3 complex required for 43S pre-initiation complex assembly and start codon recognition; its normal (wild-type) function sustains high translational output, which is associated with accelerated aging via mTOR-driven anabolism. Therefore, the normal function of egl-45 promotes translation and opposes longevity, placing it in the anti-longevity category relative to reduced-translation longevity paradigms. The key pathway is mTORC1-driven translational control through eIF3 complex activity at the 43S pre-initiation complex.
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 own reasoning actually argues for anti_longevity (egl-45 promotes translation which is associated with accelerated aging), but then contradicts itself by outputting "pro_longevity" in the final answer. The reasoning is internally inconsistent - the model correctly identifies that eIF3a/egl-45 sustains high translational output associated with accelerated aging, which would make it anti_longevity, but then labels it pro_longevity in the output field. This appears to be a confusion between "the gene promotes longevity" vs "reducing the gene's activity promotes longevity." The mechanism discussion is partially correct (translation initiation and TOR signaling are relevant), but the final classification is wrong and contradicts the model's own reasoning.
Raw API responses
solver
{
"reasoning": "egl-45 encodes the eIF3a subunit of the eukaryotic translation initiation factor 3 complex, a central regulator of cap-dependent mRNA translation. In the context of aging, global translational activity is tightly coupled to nutrient-sensing pathways, particularly TOR (mTORC1) signaling, which phosphorylates downstream effectors to promote ribosome biogenesis and translation initiation. Reduced translation initiation—through partial loss of eIF3 subunit function or TOR inhibition—is a well-established pro-longevity intervention in C. elegans and other organisms. However, egl-45/eIF3a is an essential scaffolding subunit of the eIF3 complex required for 43S pre-initiation complex assembly and start codon recognition; its normal (wild-type) function sustains high translational output, which is associated with accelerated aging via mTOR-driven anabolism. Therefore, the normal function of egl-45 promotes translation and opposes longevity, placing it in the anti-longevity category relative to reduced-translation longevity paradigms. The key pathway is mTORC1-driven translational control through eIF3 complex activity at the 43S pre-initiation complex.",
"confidence": 0.62,
"key_pathways": [
"mTORC1-eIF3 translational control",
"cap-dependent translation initiation (43S pre-initiation complex)",
"TOR nutrient-sensing pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" Interestingly, the model's own reasoning actually argues for anti_longevity (egl-45 promotes translation which is associated with accelerated aging), but then contradicts itself by outputting \"pro_longevity\" in the final answer. The reasoning is internally inconsistent - the model correctly identifies that eIF3a/egl-45 sustains high translational output associated with accelerated aging, which would make it anti_longevity, but then labels it pro_longevity in the output field. This appears to be a confusion between \"the gene promotes longevity\" vs \"reducing the gene's activity promotes longevity.\" The mechanism discussion is partially correct (translation initiation and TOR signaling are relevant), but the final classification is wrong and contradicts the model's own reasoning.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}