sem-5
C. elegans
Sex muscle abnormal protein 5
What the model saw
Gene: sem-5 Organism: Caenorhabditis elegans Known functions: Sex muscle abnormal protein 5. epidermal growth factor receptor binding. phosphotyrosine residue binding. protein binding.
View unredacted entry
Sex muscle abnormal protein 5. epidermal growth factor receptor binding. phosphotyrosine residue binding. protein binding.
Solver output
SEM-5 is the C. elegans ortholog of the mammalian GRB2 adaptor protein, which couples activated receptor tyrosine kinases (RTKs) to downstream RAS/MAPK signaling. Its molecular functions — EGF receptor binding and phosphotyrosine residue binding — place it as a critical adaptor that transduces growth factor signals from the EGF receptor (LET-23 in C. elegans) into RAS-ERK pathway activation. Hyperactivation of RTK/RAS/MAPK signaling is well established to oppose longevity in C. elegans, as it antagonizes the DAF-16/FOXO transcription factor indirectly and promotes growth and proliferation at the expense of stress resistance and lifespan extension. Loss-of-function in the EGF/RAS pathway components generally extends lifespan, meaning the normal pro-growth function of SEM-5 is anti-longevity. This places SEM-5 in the deregulated nutrient/growth-factor sensing hallmark, analogous to insulin/IGF-1-like signaling dysregulation.
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 sem-5. The mechanistic reasoning is solid: SEM-5 is indeed the GRB2 ortholog that couples EGF receptor (LET-23) signaling to RAS/MAPK pathway, and loss-of-function in this pathway generally extends lifespan, making SEM-5 anti-longevity. The mechanism class of "deregulated_nutrient_sensing" is slightly imprecise — SEM-5 operates more in EGF/RAS-MAPK signaling than insulin/nutrient sensing per se — but the model acknowledges this distinction and the overall reasoning is well-grounded. The confidence of 0.72 is appropriate given the indirect nature of the evidence.
Raw API responses
solver
{
"reasoning": "SEM-5 is the C. elegans ortholog of the mammalian GRB2 adaptor protein, which couples activated receptor tyrosine kinases (RTKs) to downstream RAS/MAPK signaling. Its molecular functions — EGF receptor binding and phosphotyrosine residue binding — place it as a critical adaptor that transduces growth factor signals from the EGF receptor (LET-23 in C. elegans) into RAS-ERK pathway activation. Hyperactivation of RTK/RAS/MAPK signaling is well established to oppose longevity in C. elegans, as it antagonizes the DAF-16/FOXO transcription factor indirectly and promotes growth and proliferation at the expense of stress resistance and lifespan extension. Loss-of-function in the EGF/RAS pathway components generally extends lifespan, meaning the normal pro-growth function of SEM-5 is anti-longevity. This places SEM-5 in the deregulated nutrient/growth-factor sensing hallmark, analogous to insulin/IGF-1-like signaling dysregulation.",
"confidence": 0.72,
"key_pathways": [
"EGF receptor / RAS-MAPK signaling",
"RTK adaptor (GRB2 ortholog) phosphotyrosine coupling",
"DAF-16/FOXO antagonism via growth factor signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for sem-5. The mechanistic reasoning is solid: SEM-5 is indeed the GRB2 ortholog that couples EGF receptor (LET-23) signaling to RAS/MAPK pathway, and loss-of-function in this pathway generally extends lifespan, making SEM-5 anti-longevity. The mechanism class of \"deregulated_nutrient_sensing\" is slightly imprecise — SEM-5 operates more in EGF/RAS-MAPK signaling than insulin/nutrient sensing per se — but the model acknowledges this distinction and the overall reasoning is well-grounded. The confidence of 0.72 is appropriate given the indirect nature of the evidence.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}