skn-1
C. elegans
BZIP domain-containing protein;Protein skinhead-1
What the model saw
Gene: skn-1 Organism: Caenorhabditis elegans Known functions: BZIP domain-containing protein;Protein skinhead-1. DNA binding. DNA-binding transcription factor activity. DNA-binding transcription factor activity, RNA polymerase II-specific. Hsp70 protein binding. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II transcription regulatory region sequence-specific DNA binding. protein binding. sequence-specific DNA binding.
View unredacted entry
BZIP domain-containing protein;Protein skinhead-1. DNA binding. DNA-binding transcription factor activity. DNA-binding transcription factor activity, RNA polymerase II-specific. Hsp70 protein binding. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II transcription regulatory region sequence-specific DNA binding. protein binding. sequence-specific DNA binding.
Solver output
SKN-1 is the C. elegans ortholog of mammalian NRF2 (Nuclear Factor Erythroid 2-Related Factor 2), a bZIP transcription factor that is a master regulator of the oxidative stress response and xenobiotic detoxification. SKN-1 binds to antioxidant response elements (AREs) in the promoters of phase II detoxification and antioxidant genes (e.g., gst, gcs-1), directly counteracting oxidative damage accumulation. Its activity is regulated by the IIS (insulin/IGF-1 signaling) pathway via DAF-16/FOXO, and SKN-1 activation — particularly in the intestine and ASI neurons — is well-established to extend lifespan in C. elegans. The Hsp70 binding annotation further supports its role in proteostatic stress responses. Loss of skn-1 shortens lifespan and reduces stress resistance, while gain-of-function or overactivation extends it, firmly placing SKN-1 as a pro-longevity factor acting through oxidative stress defense and transcriptional regulation of cytoprotective genes.
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 identifies skn-1 as pro_longevity with high confidence, and the biological reasoning about SKN-1 being the NRF2 ortholog, its role in oxidative stress response, ARE-driven transcription, and IIS pathway interactions is largely accurate. However, the model classifies the mechanism as "epigenetic_alterations," which is incorrect. SKN-1/NRF2 is a transcription factor that directly regulates gene expression through sequence-specific DNA binding — this is a transcriptional regulation mechanism, not an epigenetic alteration. Epigenetic alterations refer to changes in chromatin structure, DNA methylation, histone modifications, etc. The mechanism_class is clearly misassigned despite the detailed and mostly correct biological narrative in the reasoning text.
Raw API responses
solver
{
"reasoning": "SKN-1 is the C. elegans ortholog of mammalian NRF2 (Nuclear Factor Erythroid 2-Related Factor 2), a bZIP transcription factor that is a master regulator of the oxidative stress response and xenobiotic detoxification. SKN-1 binds to antioxidant response elements (AREs) in the promoters of phase II detoxification and antioxidant genes (e.g., gst, gcs-1), directly counteracting oxidative damage accumulation. Its activity is regulated by the IIS (insulin/IGF-1 signaling) pathway via DAF-16/FOXO, and SKN-1 activation — particularly in the intestine and ASI neurons — is well-established to extend lifespan in C. elegans. The Hsp70 binding annotation further supports its role in proteostatic stress responses. Loss of skn-1 shortens lifespan and reduces stress resistance, while gain-of-function or overactivation extends it, firmly placing SKN-1 as a pro-longevity factor acting through oxidative stress defense and transcriptional regulation of cytoprotective genes.",
"confidence": 0.95,
"key_pathways": [
"NRF2/SKN-1 oxidative stress response (ARE-driven transcription)",
"Insulin/IGF-1 signaling (IIS) - DAF-16/SKN-1 axis",
"Phase II detoxification and glutathione biosynthesis (gcs-1, gst genes)"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identifies skn-1 as pro_longevity with high confidence, and the biological reasoning about SKN-1 being the NRF2 ortholog, its role in oxidative stress response, ARE-driven transcription, and IIS pathway interactions is largely accurate. However, the model classifies the mechanism as \"epigenetic_alterations,\" which is incorrect. SKN-1/NRF2 is a transcription factor that directly regulates gene expression through sequence-specific DNA binding — this is a transcriptional regulation mechanism, not an epigenetic alteration. Epigenetic alterations refer to changes in chromatin structure, DNA methylation, histone modifications, etc. The mechanism_class is clearly misassigned despite the detailed and mostly correct biological narrative in the reasoning text.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 4,
"ground_truth_questionable": false
}