rbr-2
C. elegans
Lysine-specific demethylase rbr-2
What the model saw
Gene: rbr-2 Organism: Caenorhabditis elegans Known functions: Lysine-specific demethylase rbr-2. DNA binding. histone H3 demethylase activity. histone H3K4me/H3K4me2/H3K4me3 demethylase activity.
View unredacted entry
Lysine-specific demethylase rbr-2. DNA binding. histone H3 demethylase activity. histone H3K4me/H3K4me2/H3K4me3 demethylase activity.
Solver output
RBR-2 is the C. elegans ortholog of the KDM5/JARID1 family of histone H3K4 demethylases, which removes mono-, di-, and tri-methyl marks from H3K4. H3K4me3 is an active transcription mark associated with genes promoting longevity, including those in the insulin/IGF-1 signaling and mitochondrial pathways. Loss of H3K4me3 methyltransferase activity (e.g., loss of the SET-2/ASH-2 complex) shortens lifespan, while reduction of H3K4me3 demethylase activity (i.e., loss of rbr-2) has been shown to extend lifespan in C. elegans by maintaining elevated H3K4me3 levels at longevity-promoting gene loci. Thus, the normal function of rbr-2—removing activating H3K4 methyl marks—opposes longevity by suppressing transcription of pro-longevity genes. This places rbr-2 squarely within the epigenetic alterations hallmark of aging, specifically the regulation of active chromatin states via histone methylation dynamics.
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 ground truth classifies rbr-2's longevity influence as "unclear," but the model confidently predicts "anti_longevity" with 0.82 confidence. The model's reasoning is plausible and internally consistent — it correctly identifies rbr-2 as a H3K4 demethylase and correctly notes that H3K4me3 is associated with active transcription of pro-longevity genes. However, the actual literature on rbr-2 in C. elegans longevity is mixed/unclear, and the model overstates certainty. Some studies show rbr-2 loss extends lifespan, but the overall picture is not clear-cut enough to assign a definitive anti-longevity role. The model's mechanistic reasoning is reasonable but oversimplified, and the high confidence is unwarranted given the ambiguity in the field. The ground truth "unclear" designation reflects genuine scientific uncertainty that the model failed to capture.
Raw API responses
solver
{
"reasoning": "RBR-2 is the C. elegans ortholog of the KDM5/JARID1 family of histone H3K4 demethylases, which removes mono-, di-, and tri-methyl marks from H3K4. H3K4me3 is an active transcription mark associated with genes promoting longevity, including those in the insulin/IGF-1 signaling and mitochondrial pathways. Loss of H3K4me3 methyltransferase activity (e.g., loss of the SET-2/ASH-2 complex) shortens lifespan, while reduction of H3K4me3 demethylase activity (i.e., loss of rbr-2) has been shown to extend lifespan in C. elegans by maintaining elevated H3K4me3 levels at longevity-promoting gene loci. Thus, the normal function of rbr-2—removing activating H3K4 methyl marks—opposes longevity by suppressing transcription of pro-longevity genes. This places rbr-2 squarely within the epigenetic alterations hallmark of aging, specifically the regulation of active chromatin states via histone methylation dynamics.",
"confidence": 0.82,
"key_pathways": [
"H3K4me3 histone demethylation",
"epigenetic regulation of longevity gene expression",
"chromatin remodeling / KDM5 family demethylase activity"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The ground truth classifies rbr-2's longevity influence as \"unclear,\" but the model confidently predicts \"anti_longevity\" with 0.82 confidence. The model's reasoning is plausible and internally consistent — it correctly identifies rbr-2 as a H3K4 demethylase and correctly notes that H3K4me3 is associated with active transcription of pro-longevity genes. However, the actual literature on rbr-2 in C. elegans longevity is mixed/unclear, and the model overstates certainty. Some studies show rbr-2 loss extends lifespan, but the overall picture is not clear-cut enough to assign a definitive anti-longevity role. The model's mechanistic reasoning is reasonable but oversimplified, and the high confidence is unwarranted given the ambiguity in the field. The ground truth \"unclear\" designation reflects genuine scientific uncertainty that the model failed to capture.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}