eif-2gamma
C. elegans
protein-synthesizing GTPase
What the model saw
Gene: eif-2gamma Organism: Caenorhabditis elegans Known functions: protein-synthesizing GTPase. GTP binding. GTPase activity. tRNA binding. translation initiation factor activity.
View unredacted entry
protein-synthesizing GTPase. GTP binding. GTPase activity. tRNA binding. translation initiation factor activity.
Solver output
eif-2gamma encodes the gamma subunit of eukaryotic initiation factor 2 (eIF2), a GTPase that is essential for the delivery of initiator Met-tRNA to the ribosome during translation initiation. Its GTP-binding and GTPase activities drive the formation of the ternary complex (eIF2·GTP·Met-tRNAi), a rate-limiting step in global protein synthesis. High translational activity is tightly coupled to nutrient-sensing pathways (mTORC1/TOR signaling), and elevated global translation is well-established as anti-longevity in C. elegans; reducing translation initiation—including via eIF2 pathway modulation—extends lifespan. Phosphorylation of the eIF2α subunit (integrated stress response) reduces ternary complex availability and globally attenuates translation, which is pro-longevity, meaning the active, unimpeded function of eIF2 (promoted by eif-2gamma) opposes this beneficial attenuation. Consistent with this, RNAi knockdown of translation initiation factors in C. elegans, including eIF2 subunits, extends lifespan, placing normal eif-2gamma function in the anti-longevity category.
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 correctly predicted anti_longevity for eif-2gamma. The mechanistic reasoning is sound: eif-2gamma promotes translation initiation via eIF2 ternary complex formation, and reducing global translation (including via RNAi knockdown of translation initiation factors) extends lifespan in C. elegans. The model correctly connects eIF2 function to anti-longevity through the well-established translation-longevity axis. The mechanism_class of "deregulated_nutrient_sensing" is somewhat imprecise — the more direct mechanism is translational control rather than nutrient sensing per se — but the overall reasoning is coherent and well-supported. Confidence of 0.75 is appropriate given the indirect nature of some of the evidence cited.
Raw API responses
solver
{
"reasoning": "eif-2gamma encodes the gamma subunit of eukaryotic initiation factor 2 (eIF2), a GTPase that is essential for the delivery of initiator Met-tRNA to the ribosome during translation initiation. Its GTP-binding and GTPase activities drive the formation of the ternary complex (eIF2·GTP·Met-tRNAi), a rate-limiting step in global protein synthesis. High translational activity is tightly coupled to nutrient-sensing pathways (mTORC1/TOR signaling), and elevated global translation is well-established as anti-longevity in C. elegans; reducing translation initiation—including via eIF2 pathway modulation—extends lifespan. Phosphorylation of the eIF2α subunit (integrated stress response) reduces ternary complex availability and globally attenuates translation, which is pro-longevity, meaning the active, unimpeded function of eIF2 (promoted by eif-2gamma) opposes this beneficial attenuation. Consistent with this, RNAi knockdown of translation initiation factors in C. elegans, including eIF2 subunits, extends lifespan, placing normal eif-2gamma function in the anti-longevity category.",
"confidence": 0.75,
"key_pathways": [
"eIF2 ternary complex formation / translation initiation",
"mTOR/nutrient-sensing translational control",
"integrated stress response (eIF2α phosphorylation)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for eif-2gamma. The mechanistic reasoning is sound: eif-2gamma promotes translation initiation via eIF2 ternary complex formation, and reducing global translation (including via RNAi knockdown of translation initiation factors) extends lifespan in C. elegans. The model correctly connects eIF2 function to anti-longevity through the well-established translation-longevity axis. The mechanism_class of \"deregulated_nutrient_sensing\" is somewhat imprecise — the more direct mechanism is translational control rather than nutrient sensing per se — but the overall reasoning is coherent and well-supported. Confidence of 0.75 is appropriate given the indirect nature of some of the evidence cited.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}