ife-2
C. elegans
Eukaryotic translation initiation factor 4E-2
What the model saw
Gene: ife-2 Organism: Caenorhabditis elegans Known functions: Eukaryotic translation initiation factor 4E-2. RNA 7-methylguanosine cap binding. RNA binding. RNA trimethylguanosine cap binding. protein binding. translation initiation factor activity.
View unredacted entry
Eukaryotic translation initiation factor 4E-2. RNA 7-methylguanosine cap binding. RNA binding. RNA trimethylguanosine cap binding. protein binding. translation initiation factor activity.
Solver output
ife-2 encodes the C. elegans eIF4E-2 isoform, a cap-binding translation initiation factor that recognizes the 7-methylguanosine (m7G) and trimethylguanosine (TMG) caps on mRNAs to recruit the ribosome. Reduction of global translational activity via downregulation of eIF4E family members is a well-established pro-longevity intervention in C. elegans; loss-of-function of ife-2 specifically extends lifespan by reducing overall protein synthesis rates. This connects to the nutrient-sensing/TOR signaling axis, as mTORC1 promotes cap-dependent translation through 4E-BP and S6K, and reducing eIF4E activity phenocopies mTOR inhibition. Decreased translational output reduces the burden on proteostasis machinery and dampens anabolic signaling, both of which are associated with lifespan extension. The pro-longevity effect here is paradoxical in that the gene's normal function (promoting translation) is anti-longevity, but the gene itself, when functioning normally at reduced levels or when knocked down, extends life — consistent with the classification that its normal activity opposes longevity.
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 is internally contradictory and confused. It correctly notes that loss-of-function of ife-2 extends lifespan, but then classifies the gene as "pro_longevity" — which is backwards. In GenAge's classification system, a gene is "anti_longevity" when its normal function opposes longevity (i.e., loss-of-function extends lifespan). The model even acknowledges this in its reasoning ("the gene's normal function (promoting translation) is anti-longevity") but then incorrectly labels the gene as "pro_longevity." The model confused the effect of the gene's activity with the classification of the gene itself. The mechanistic description of ife-2 as a cap-binding translation initiation factor connected to mTOR/TOR signaling is broadly correct, but the final classification is wrong and the reasoning is self-contradictory. High confidence (0.82) on a wrong answer makes this a confident_wrong failure.
Raw API responses
solver
{
"reasoning": "ife-2 encodes the C. elegans eIF4E-2 isoform, a cap-binding translation initiation factor that recognizes the 7-methylguanosine (m7G) and trimethylguanosine (TMG) caps on mRNAs to recruit the ribosome. Reduction of global translational activity via downregulation of eIF4E family members is a well-established pro-longevity intervention in C. elegans; loss-of-function of ife-2 specifically extends lifespan by reducing overall protein synthesis rates. This connects to the nutrient-sensing/TOR signaling axis, as mTORC1 promotes cap-dependent translation through 4E-BP and S6K, and reducing eIF4E activity phenocopies mTOR inhibition. Decreased translational output reduces the burden on proteostasis machinery and dampens anabolic signaling, both of which are associated with lifespan extension. The pro-longevity effect here is paradoxical in that the gene's normal function (promoting translation) is anti-longevity, but the gene itself, when functioning normally at reduced levels or when knocked down, extends life — consistent with the classification that its normal activity opposes longevity.",
"confidence": 0.82,
"key_pathways": [
"cap-dependent translation initiation (eIF4E/mTOR axis)",
"TOR nutrient-sensing signaling",
"global protein synthesis rate regulation"
],
"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 is internally contradictory and confused. It correctly notes that loss-of-function of ife-2 extends lifespan, but then classifies the gene as \"pro_longevity\" — which is backwards. In GenAge's classification system, a gene is \"anti_longevity\" when its normal function opposes longevity (i.e., loss-of-function extends lifespan). The model even acknowledges this in its reasoning (\"the gene's normal function (promoting translation) is anti-longevity\") but then incorrectly labels the gene as \"pro_longevity.\" The model confused the effect of the gene's activity with the classification of the gene itself. The mechanistic description of ife-2 as a cap-binding translation initiation factor connected to mTOR/TOR signaling is broadly correct, but the final classification is wrong and the reasoning is self-contradictory. High confidence (0.82) on a wrong answer makes this a confident_wrong failure.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}