rheb-1
C. elegans
GTP-binding protein Rheb homolog 1
What the model saw
Gene: rheb-1 Organism: Caenorhabditis elegans Known functions: GTP-binding protein Rheb homolog 1. GTP binding. GTPase activity. protein serine/threonine kinase activator activity.
View unredacted entry
GTP-binding protein Rheb homolog 1. GTP binding. GTPase activity. protein serine/threonine kinase activator activity.
Solver output
RHEB-1 is a Ras-family GTPase that, in its GTP-bound active state, directly binds to and activates TORC1 (Target of Rapamycin Complex 1) via its protein serine/threonine kinase activator activity — specifically stimulating the kinase activity of LET-363/TOR. TORC1 is the central hub of nutrient-sensing signaling; its activation promotes anabolic processes (protein synthesis, growth) and suppresses autophagy, both of which are associated with shortened lifespan in C. elegans. Loss-of-function in the TOR pathway (e.g., reduced let-363/TOR or rsks-1/S6K) extends lifespan in C. elegans, placing rheb-1 as a pro-aging activator of this pathway. RHEB-1 is itself negatively regulated by the TSC1/TSC2 GAP complex, which integrates upstream signals (insulin/IGF-1, energy status) to modulate TORC1 activity. Thus, the normal function of rheb-1 — activating TORC1 — opposes longevity by suppressing autophagy and promoting nutrient-driven growth signaling.
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 rheb-1 in C. elegans with high confidence (0.88). The mechanistic reasoning is excellent and accurate: RHEB-1 is a GTPase that activates TORC1/TOR signaling, which promotes growth and suppresses autophagy, thereby shortening lifespan. The model correctly identifies the TSC1/TSC2 regulatory axis, the downstream effects on S6K and autophagy, and correctly places rheb-1 as a pro-aging gene in the nutrient-sensing pathway. The reasoning is detailed, biologically accurate, and well-supported by the known literature on TOR signaling in C. elegans longevity.
Raw API responses
solver
{
"reasoning": "RHEB-1 is a Ras-family GTPase that, in its GTP-bound active state, directly binds to and activates TORC1 (Target of Rapamycin Complex 1) via its protein serine/threonine kinase activator activity — specifically stimulating the kinase activity of LET-363/TOR. TORC1 is the central hub of nutrient-sensing signaling; its activation promotes anabolic processes (protein synthesis, growth) and suppresses autophagy, both of which are associated with shortened lifespan in C. elegans. Loss-of-function in the TOR pathway (e.g., reduced let-363/TOR or rsks-1/S6K) extends lifespan in C. elegans, placing rheb-1 as a pro-aging activator of this pathway. RHEB-1 is itself negatively regulated by the TSC1/TSC2 GAP complex, which integrates upstream signals (insulin/IGF-1, energy status) to modulate TORC1 activity. Thus, the normal function of rheb-1 — activating TORC1 — opposes longevity by suppressing autophagy and promoting nutrient-driven growth signaling.",
"confidence": 0.88,
"key_pathways": [
"TOR/TORC1 signaling",
"Nutrient sensing (RHEB-TSC-mTOR axis)",
"Autophagy suppression"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for rheb-1 in C. elegans with high confidence (0.88). The mechanistic reasoning is excellent and accurate: RHEB-1 is a GTPase that activates TORC1/TOR signaling, which promotes growth and suppresses autophagy, thereby shortening lifespan. The model correctly identifies the TSC1/TSC2 regulatory axis, the downstream effects on S6K and autophagy, and correctly places rheb-1 as a pro-aging gene in the nutrient-sensing pathway. The reasoning is detailed, biologically accurate, and well-supported by the known literature on TOR signaling in C. elegans longevity.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}