Per2
M. musculus
period circadian clock 2
What the model saw
Gene: Per2 Organism: Mus musculus Known functions: period circadian clock 2. period circadian protein homolog 2. DNA-binding transcription factor binding. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase binding. histone deacetylase binding. histone methyltransferase binding. identical protein binding. kinase binding. nuclear receptor binding. pre-mRNA binding. protein binding. transcription cis-regulatory region binding. transcription coactivator activity. transcription corepressor binding. transcription regulator inhibitor activity.
View unredacted entry
period circadian clock 2. period circadian protein homolog 2. DNA-binding transcription factor binding. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase binding. histone deacetylase binding. histone methyltransferase binding. identical protein binding. kinase binding. nuclear receptor binding. pre-mRNA binding. protein binding. transcription cis-regulatory region binding. transcription coactivator activity. transcription corepressor binding. transcription regulator inhibitor activity.
Solver output
PER2 is a core component of the circadian clock negative feedback loop, functioning as a transcription corepressor/inhibitor that suppresses CLOCK/BMAL1-driven transcription. Its binding to histone deacetylases and histone methyltransferases links circadian timekeeping directly to chromatin remodeling and epigenetic regulation, which deteriorates with age. Disruption of circadian rhythmicity (as occurs in Per2 loss-of-function) is associated with accelerated aging phenotypes, increased cancer susceptibility, and metabolic dysfunction in mice. PER2 also interacts with nuclear receptors and RNA Pol II machinery, coordinating temporal gene expression programs that maintain metabolic homeostasis and DNA damage responses. Intact PER2 function thus supports the circadian regulation of genome maintenance and metabolic pathways that collectively oppose aging hallmarks, placing its normal function in the pro-longevity category.
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 "pro_longevity" but the ground truth is "anti_longevity." Per2 mutant mice actually show extended lifespan in some studies, which is why it's classified as anti_longevity (loss of Per2 can promote longevity). The model's reasoning conflates "disruption of circadian rhythmicity is bad" with "Per2 must be pro-longevity," but the actual experimental evidence in mice shows the opposite — Per2 mutations/loss can extend lifespan, making Per2 anti_longevity. The model's mechanistic reasoning about circadian clock function is partially correct in general terms, but it draws the wrong conclusion about the direction of Per2's effect on longevity. The model was moderately confident (0.62) in the wrong direction.
Raw API responses
solver
{
"reasoning": "PER2 is a core component of the circadian clock negative feedback loop, functioning as a transcription corepressor/inhibitor that suppresses CLOCK/BMAL1-driven transcription. Its binding to histone deacetylases and histone methyltransferases links circadian timekeeping directly to chromatin remodeling and epigenetic regulation, which deteriorates with age. Disruption of circadian rhythmicity (as occurs in Per2 loss-of-function) is associated with accelerated aging phenotypes, increased cancer susceptibility, and metabolic dysfunction in mice. PER2 also interacts with nuclear receptors and RNA Pol II machinery, coordinating temporal gene expression programs that maintain metabolic homeostasis and DNA damage responses. Intact PER2 function thus supports the circadian regulation of genome maintenance and metabolic pathways that collectively oppose aging hallmarks, placing its normal function in the pro-longevity category.",
"confidence": 0.62,
"key_pathways": [
"Circadian clock negative feedback loop (CLOCK/BMAL1 repression)",
"Histone deacetylase/methyltransferase-mediated chromatin remodeling",
"Nuclear receptor-mediated metabolic regulation"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" Per2 mutant mice actually show extended lifespan in some studies, which is why it's classified as anti_longevity (loss of Per2 can promote longevity). The model's reasoning conflates \"disruption of circadian rhythmicity is bad\" with \"Per2 must be pro-longevity,\" but the actual experimental evidence in mice shows the opposite — Per2 mutations/loss can extend lifespan, making Per2 anti_longevity. The model's mechanistic reasoning about circadian clock function is partially correct in general terms, but it draws the wrong conclusion about the direction of Per2's effect on longevity. The model was moderately confident (0.62) in the wrong direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}