RAS2
S. cerevisiae
Ras family GTPase RAS2
What the model saw
Gene: RAS2 Organism: Saccharomyces cerevisiae Known functions: Ras family GTPase RAS2. G protein activity. GTP binding. GTPase activity. protein binding.
View unredacted entry
Ras family GTPase RAS2. G protein activity. GTP binding. GTPase activity. protein binding.
Solver output
RAS2 encodes a small GTPase that, in its GTP-bound active state, stimulates adenylyl cyclase (Cyr1) to produce cAMP, thereby activating the PKA (cAMP-PKA) pathway. Hyperactivation of the RAS/cAMP/PKA axis suppresses stress-response transcription factors (Msn2/Msn4), inhibits autophagy, and promotes anabolic growth at the expense of stress resistance and longevity. In yeast, loss-of-function or dominant-negative alleles of RAS2 (e.g., ras2Δ) extend both chronological and replicative lifespan, while constitutively active RAS2(G19V) shortens lifespan. This places RAS2 squarely in the nutrient-sensing axis alongside TOR and Sch9, where its normal pro-growth signaling 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 "anti_longevity" with high confidence (0.92), but the ground truth is "unclear." The mechanistic reasoning is well-articulated and largely accurate — RAS2 does activate the cAMP/PKA pathway, and ras2Δ has been shown to extend chronological lifespan in some studies. However, the literature on RAS2 and longevity in yeast is more nuanced and contradictory than the model suggests. For replicative lifespan, the evidence is mixed, and the GenAge curators assigned "unclear" rather than "anti_longevity." The model was overconfident in its classification, failing to acknowledge the ambiguity in the literature. The mechanistic description itself is reasonable and directionally correct for chronological lifespan, but the overall classification is wrong per the ground truth.
Raw API responses
solver
{
"reasoning": "RAS2 encodes a small GTPase that, in its GTP-bound active state, stimulates adenylyl cyclase (Cyr1) to produce cAMP, thereby activating the PKA (cAMP-PKA) pathway. Hyperactivation of the RAS/cAMP/PKA axis suppresses stress-response transcription factors (Msn2/Msn4), inhibits autophagy, and promotes anabolic growth at the expense of stress resistance and longevity. In yeast, loss-of-function or dominant-negative alleles of RAS2 (e.g., ras2Δ) extend both chronological and replicative lifespan, while constitutively active RAS2(G19V) shortens lifespan. This places RAS2 squarely in the nutrient-sensing axis alongside TOR and Sch9, where its normal pro-growth signaling opposes longevity.",
"confidence": 0.92,
"key_pathways": [
"RAS/cAMP/PKA signaling",
"nutrient sensing and stress response",
"autophagy suppression via PKA"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted \"anti_longevity\" with high confidence (0.92), but the ground truth is \"unclear.\" The mechanistic reasoning is well-articulated and largely accurate — RAS2 does activate the cAMP/PKA pathway, and ras2Δ has been shown to extend chronological lifespan in some studies. However, the literature on RAS2 and longevity in yeast is more nuanced and contradictory than the model suggests. For replicative lifespan, the evidence is mixed, and the GenAge curators assigned \"unclear\" rather than \"anti_longevity.\" The model was overconfident in its classification, failing to acknowledge the ambiguity in the literature. The mechanistic description itself is reasonable and directionally correct for chronological lifespan, but the overall classification is wrong per the ground truth.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": true
}