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ife-1

C. elegans

Eukaryotic translation initiation factor 4E-1;eIF-4F 25 kDa subunit

What the model saw

Gene: ife-1
Organism: Caenorhabditis elegans
Known functions: Eukaryotic translation initiation factor 4E-1;eIF-4F 25 kDa subunit. 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-1;eIF-4F 25 kDa subunit. RNA 7-methylguanosine cap binding. RNA binding. RNA trimethylguanosine cap binding. protein binding. translation initiation factor activity.

Solver output

Predicted influence
Unclear
Confidence
45%
Mechanism
Deregulated nutrient sensing
Reasoning

ife-1 encodes one of five eIF4E paralogs in C. elegans, functioning as the cap-binding subunit of the eIF4F translation initiation complex. Reduced global translation is a well-established pro-longevity mechanism in C. elegans (e.g., knockdown of ife-2 extends lifespan), operating downstream of nutrient-sensing pathways such as TOR/TORC1, which phosphorylates 4E-BP to release eIF4E and promote cap-dependent translation. However, ife-1 is a specific paralog with preferential expression in the germline and distinct substrate specificity compared to ife-2 or ife-3; its loss does not consistently extend lifespan in the same manner as ife-2 knockdown. Because the longevity effect of eIF4E paralogs in C. elegans is highly paralog-specific, and ife-1's primary role appears germline-restricted rather than somatic, the net influence on organismal longevity is genuinely ambiguous without additional context.

Key pathways
eIF4F cap-dependent translation initiationTOR/TORC1 nutrient sensinggermline translation regulation
Longevity influence
Anti-longevity
Lifespan effect
Increase

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

Answer
Incorrect
Mechanism
Incorrect
Reasoning quality
3/5
Failure mode
Appropriately uncertain
Notes

The model predicted "unclear" while the ground truth is "anti_longevity" (meaning ife-1 promotes longevity when lost, i.e., its normal function shortens lifespan). The model correctly identified that ife-1 is a germline-expressed eIF4E paralog and that different paralogs have different longevity effects, but it failed to commit to the correct answer. The model's reasoning about paralog-specificity is sound but incomplete - it knew ife-2 knockdown extends lifespan but didn't extend this logic to conclude ife-1 is likely also anti-longevity. The mechanism class of "deregulated_nutrient_sensing" is partially relevant (TOR pathway connection) but not the most precise framing. The model's uncertainty was somewhat reasonable given the paralog complexity, but the ground truth indicates ife-1 is clearly anti-longevity, suggesting the model should have leaned more toward that conclusion given the general principle that translation initiation factors tend to be anti-longevity in C. elegans.

Raw API responses

solver

{
  "reasoning": "ife-1 encodes one of five eIF4E paralogs in C. elegans, functioning as the cap-binding subunit of the eIF4F translation initiation complex. Reduced global translation is a well-established pro-longevity mechanism in C. elegans (e.g., knockdown of ife-2 extends lifespan), operating downstream of nutrient-sensing pathways such as TOR/TORC1, which phosphorylates 4E-BP to release eIF4E and promote cap-dependent translation. However, ife-1 is a specific paralog with preferential expression in the germline and distinct substrate specificity compared to ife-2 or ife-3; its loss does not consistently extend lifespan in the same manner as ife-2 knockdown. Because the longevity effect of eIF4E paralogs in C. elegans is highly paralog-specific, and ife-1's primary role appears germline-restricted rather than somatic, the net influence on organismal longevity is genuinely ambiguous without additional context.",
  "confidence": 0.45,
  "key_pathways": [
    "eIF4F cap-dependent translation initiation",
    "TOR/TORC1 nutrient sensing",
    "germline translation regulation"
  ],
  "mechanism_class": "deregulated_nutrient_sensing",
  "longevity_influence": "unclear"
}

advisor

{
  "notes": "The model predicted \"unclear\" while the ground truth is \"anti_longevity\" (meaning ife-1 promotes longevity when lost, i.e., its normal function shortens lifespan). The model correctly identified that ife-1 is a germline-expressed eIF4E paralog and that different paralogs have different longevity effects, but it failed to commit to the correct answer. The model's reasoning about paralog-specificity is sound but incomplete - it knew ife-2 knockdown extends lifespan but didn't extend this logic to conclude ife-1 is likely also anti-longevity. The mechanism class of \"deregulated_nutrient_sensing\" is partially relevant (TOR pathway connection) but not the most precise framing. The model's uncertainty was somewhat reasonable given the paralog complexity, but the ground truth indicates ife-1 is clearly anti-longevity, suggesting the model should have leaned more toward that conclusion given the general principle that translation initiation factors tend to be anti-longevity in C. elegans.",
  "failure_mode": "appropriately_uncertain",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 3,
  "ground_truth_questionable": false
}