shc-1
C. elegans
SHC-transforming protein homolog 1
What the model saw
Gene: shc-1 Organism: Caenorhabditis elegans Known functions: SHC-transforming protein homolog 1. insulin-like growth factor receptor binding. mitogen-activated protein kinase kinase binding. mitogen-activated protein kinase kinase kinase binding. protein binding.
View unredacted entry
SHC-transforming protein homolog 1. insulin-like growth factor receptor binding. mitogen-activated protein kinase kinase binding. mitogen-activated protein kinase kinase kinase binding. protein binding.
Solver output
SHC-1 is a SHC-transforming protein homolog that binds the insulin-like growth factor receptor (IGF-1R/DAF-2 in C. elegans), acting as an adaptor that couples receptor activation to downstream signaling. In the canonical IIS (insulin/IGF-1 signaling) pathway, SHC adaptor proteins recruit GRB2/SOS complexes to activated receptors, promoting RAS-MAPK cascade activation (consistent with its MAPKKK and MAPKK binding activities). Elevated IIS signaling suppresses DAF-16/FOXO nuclear localization, reducing expression of stress-resistance and longevity genes. Loss-of-function in IIS pathway components (e.g., daf-2) dramatically extends lifespan in C. elegans, meaning that shc-1, as a positive transducer of IIS, would normally act to shorten lifespan. Its dual role in both IIS and MAPK cascade activation further reinforces a pro-growth, anti-longevity signaling function.
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 (0.82), but the ground truth is pro_longevity. The model's reasoning follows a plausible but incorrect logic: it assumes SHC-1 acts as a positive transducer of IIS signaling (like mammalian SHC proteins), which would make it anti-longevity. However, in C. elegans, shc-1 actually promotes longevity. Research has shown that SHC-1 in C. elegans acts differently from its mammalian counterparts - it functions in a stress-response context and its loss reduces lifespan rather than extending it. The model's mechanistic reasoning about SHC proteins coupling IGF-1R to RAS-MAPK and suppressing DAF-16 is based on mammalian biology and does not correctly apply to C. elegans shc-1. The model was confidently wrong about both the direction of effect and the underlying mechanism.
Raw API responses
solver
{
"reasoning": "SHC-1 is a SHC-transforming protein homolog that binds the insulin-like growth factor receptor (IGF-1R/DAF-2 in C. elegans), acting as an adaptor that couples receptor activation to downstream signaling. In the canonical IIS (insulin/IGF-1 signaling) pathway, SHC adaptor proteins recruit GRB2/SOS complexes to activated receptors, promoting RAS-MAPK cascade activation (consistent with its MAPKKK and MAPKK binding activities). Elevated IIS signaling suppresses DAF-16/FOXO nuclear localization, reducing expression of stress-resistance and longevity genes. Loss-of-function in IIS pathway components (e.g., daf-2) dramatically extends lifespan in C. elegans, meaning that shc-1, as a positive transducer of IIS, would normally act to shorten lifespan. Its dual role in both IIS and MAPK cascade activation further reinforces a pro-growth, anti-longevity signaling function.",
"confidence": 0.82,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) / DAF-2 pathway",
"RAS-MAPK cascade",
"DAF-16/FOXO transcription factor regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity with high confidence (0.82), but the ground truth is pro_longevity. The model's reasoning follows a plausible but incorrect logic: it assumes SHC-1 acts as a positive transducer of IIS signaling (like mammalian SHC proteins), which would make it anti-longevity. However, in C. elegans, shc-1 actually promotes longevity. Research has shown that SHC-1 in C. elegans acts differently from its mammalian counterparts - it functions in a stress-response context and its loss reduces lifespan rather than extending it. The model's mechanistic reasoning about SHC proteins coupling IGF-1R to RAS-MAPK and suppressing DAF-16 is based on mammalian biology and does not correctly apply to C. elegans shc-1. The model was confidently wrong about both the direction of effect and the underlying mechanism.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}