set9
S. pombe
histone lysine H4-K20 methyltransferase Set9
What the model saw
Gene: set9 Organism: Schizosaccharomyces pombe Known functions: histone lysine H4-K20 methyltransferase Set9. histone H4K20 methyltransferase activity. histone H4K20 trimethyltransferase activity. histone binding. nucleosome binding. protein binding.
View unredacted entry
histone lysine H4-K20 methyltransferase Set9. histone H4K20 methyltransferase activity. histone H4K20 trimethyltransferase activity. histone binding. nucleosome binding. protein binding.
Solver output
Set9 is the sole H4K20 methyltransferase in S. pombe, catalyzing mono-, di-, and trimethylation of histone H4 at lysine 20 (H4K20me1/2/3). H4K20 methylation is a critical epigenetic mark with well-established roles in DNA damage response, chromatin compaction, and genome integrity maintenance. H4K20me2/3 specifically recruits 53BP1/Crb2 to DNA double-strand breaks, facilitating repair and suppressing genomic instability. Loss of H4K20 methylation is associated with global chromatin decompaction and impaired DNA repair, both hallmarks of aging. Additionally, H4K20me1 regulates transcriptional silencing at repetitive elements, and its maintenance is linked to healthspan in multiple organisms. The pro-longevity role is supported by the gene's function in preserving epigenetic integrity and enabling efficient DNA damage 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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning focused on the protective roles of H4K20 methylation (DNA repair, chromatin compaction, genome integrity), which led it to conclude Set9 promotes longevity. However, in S. pombe, Set9 is actually anti-longevity — its deletion extends lifespan. The model failed to consider that H4K20 methylation by Set9 may promote aging rather than prevent it, possibly through mechanisms like transcriptional repression of stress response genes or other aging-promoting chromatin states. The model was moderately confident (0.72) in the wrong direction, and the mechanistic reasoning, while plausible in general terms, does not reflect the actual biology in S. pombe where set9 loss extends lifespan.
Raw API responses
solver
{
"reasoning": "Set9 is the sole H4K20 methyltransferase in S. pombe, catalyzing mono-, di-, and trimethylation of histone H4 at lysine 20 (H4K20me1/2/3). H4K20 methylation is a critical epigenetic mark with well-established roles in DNA damage response, chromatin compaction, and genome integrity maintenance. H4K20me2/3 specifically recruits 53BP1/Crb2 to DNA double-strand breaks, facilitating repair and suppressing genomic instability. Loss of H4K20 methylation is associated with global chromatin decompaction and impaired DNA repair, both hallmarks of aging. Additionally, H4K20me1 regulates transcriptional silencing at repetitive elements, and its maintenance is linked to healthspan in multiple organisms. The pro-longevity role is supported by the gene's function in preserving epigenetic integrity and enabling efficient DNA damage signaling.",
"confidence": 0.72,
"key_pathways": [
"H4K20 methylation / chromatin compaction",
"DNA double-strand break repair (Crb2/53BP1 recruitment)",
"epigenetic silencing of repetitive elements"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning focused on the protective roles of H4K20 methylation (DNA repair, chromatin compaction, genome integrity), which led it to conclude Set9 promotes longevity. However, in S. pombe, Set9 is actually anti-longevity — its deletion extends lifespan. The model failed to consider that H4K20 methylation by Set9 may promote aging rather than prevent it, possibly through mechanisms like transcriptional repression of stress response genes or other aging-promoting chromatin states. The model was moderately confident (0.72) in the wrong direction, and the mechanistic reasoning, while plausible in general terms, does not reflect the actual biology in S. pombe where set9 loss extends lifespan.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}