ROM2
S. cerevisiae
Rho family guanine nucleotide exchange factor ROM2
What the model saw
Gene: ROM2 Organism: Saccharomyces cerevisiae Known functions: Rho family guanine nucleotide exchange factor ROM2. guanyl-nucleotide exchange factor activity. phosphatidylinositol-4,5-bisphosphate binding. protein binding.
View unredacted entry
Rho family guanine nucleotide exchange factor ROM2. guanyl-nucleotide exchange factor activity. phosphatidylinositol-4,5-bisphosphate binding. protein binding.
Solver output
ROM2 is a guanine nucleotide exchange factor (GEF) for Rho1 GTPase in S. cerevisiae, activating Rho1 by catalyzing GDP-to-GTP exchange. Active Rho1 stimulates the cell wall integrity (CWI) pathway via PKC1/Slt2 MAPK signaling, and also directly activates the glucan synthase Fks1. Critically, Rho1/PKC1 signaling intersects with TORC1-mediated nutrient sensing: ROM2 is activated downstream of PIP2 binding at the plasma membrane and feeds into anabolic growth signaling. Hyperactivation of this axis promotes cell growth and proliferation at the expense of stress resistance and longevity, analogous to how excess TOR/PKC signaling shortens lifespan. Loss-of-function mutations in the Rho1-PKC pathway or its upstream activators have been associated with extended chronological and replicative lifespan in yeast, consistent with ROM2 acting as an anti-longevity factor by sustaining pro-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 ROM2 as anti_longevity. The mechanistic reasoning is sound and well-grounded: ROM2 as a GEF for Rho1, activating the CWI/PKC1 pathway, and its connection to pro-growth signaling that shortens lifespan is biologically plausible. The model also correctly notes ROM2's PIP2 binding activity (which matches the known functions listed). The reasoning about TORC1 intersection is somewhat speculative but not incorrect. Confidence of 0.62 is appropriately calibrated given the indirect evidence. Overall a strong prediction with good mechanistic support.
Raw API responses
solver
{
"reasoning": "ROM2 is a guanine nucleotide exchange factor (GEF) for Rho1 GTPase in S. cerevisiae, activating Rho1 by catalyzing GDP-to-GTP exchange. Active Rho1 stimulates the cell wall integrity (CWI) pathway via PKC1/Slt2 MAPK signaling, and also directly activates the glucan synthase Fks1. Critically, Rho1/PKC1 signaling intersects with TORC1-mediated nutrient sensing: ROM2 is activated downstream of PIP2 binding at the plasma membrane and feeds into anabolic growth signaling. Hyperactivation of this axis promotes cell growth and proliferation at the expense of stress resistance and longevity, analogous to how excess TOR/PKC signaling shortens lifespan. Loss-of-function mutations in the Rho1-PKC pathway or its upstream activators have been associated with extended chronological and replicative lifespan in yeast, consistent with ROM2 acting as an anti-longevity factor by sustaining pro-growth signaling.",
"confidence": 0.62,
"key_pathways": [
"Rho1-PKC1 cell wall integrity (CWI) signaling",
"TORC1-nutrient sensing axis",
"PIP2-mediated plasma membrane signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted ROM2 as anti_longevity. The mechanistic reasoning is sound and well-grounded: ROM2 as a GEF for Rho1, activating the CWI/PKC1 pathway, and its connection to pro-growth signaling that shortens lifespan is biologically plausible. The model also correctly notes ROM2's PIP2 binding activity (which matches the known functions listed). The reasoning about TORC1 intersection is somewhat speculative but not incorrect. Confidence of 0.62 is appropriately calibrated given the indirect evidence. Overall a strong prediction with good mechanistic support.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}