wdr-5.1
C. elegans
WD repeat-containing protein wdr-5.1
What the model saw
Gene: wdr-5.1 Organism: Caenorhabditis elegans Known functions: WD repeat-containing protein wdr-5.1. RNA polymerase II-specific DNA-binding transcription factor binding. histone reader activity. protein binding.
View unredacted entry
WD repeat-containing protein wdr-5.1. RNA polymerase II-specific DNA-binding transcription factor binding. histone reader activity. protein binding.
Solver output
WDR-5.1 is the C. elegans ortholog of mammalian WDR5, a core component of the COMPASS/SET1 and MLL histone methyltransferase complexes responsible for H3K4 methylation. Its annotated "histone reader activity" and RNA Pol II transcription factor binding indicate it functions as a scaffold that recruits H3K4 methyltransferase activity to active gene promoters. H3K4me3 is a key activating epigenetic mark, and the COMPASS complex in C. elegans (including SET-2/SET-16) has been shown to regulate lifespan; loss of H3K4 methylation machinery components (e.g., ash-2, set-2) extends lifespan, suggesting that active H3K4 methylation promotes normal aging. However, WDR-5.1 specifically has been reported to be required for longevity in certain contexts (e.g., germline-mediated longevity), acting as a pro-longevity factor by maintaining proper transcriptional programs. Its role as a histone reader and transcriptional co-activator places it squarely within epigenetic regulation of gene expression relevant to aging.
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 is internally contradictory - it correctly notes that loss of H3K4 methylation machinery (ash-2, set-2) extends lifespan, which would make WDR-5.1 (as part of the same complex) anti-longevity, not pro-longevity. The model then pivots to claim WDR-5.1 is "required for longevity in certain contexts" without strong justification, contradicting its own mechanistic reasoning. The correct conclusion from the model's own mechanistic description should have been anti_longevity (since WDR-5.1 promotes H3K4 methylation, and reducing H3K4 methylation extends lifespan). The model had the right mechanistic framework but drew the wrong conclusion, and did so with 0.72 confidence.
Raw API responses
solver
{
"reasoning": "WDR-5.1 is the C. elegans ortholog of mammalian WDR5, a core component of the COMPASS/SET1 and MLL histone methyltransferase complexes responsible for H3K4 methylation. Its annotated \"histone reader activity\" and RNA Pol II transcription factor binding indicate it functions as a scaffold that recruits H3K4 methyltransferase activity to active gene promoters. H3K4me3 is a key activating epigenetic mark, and the COMPASS complex in C. elegans (including SET-2/SET-16) has been shown to regulate lifespan; loss of H3K4 methylation machinery components (e.g., ash-2, set-2) extends lifespan, suggesting that active H3K4 methylation promotes normal aging. However, WDR-5.1 specifically has been reported to be required for longevity in certain contexts (e.g., germline-mediated longevity), acting as a pro-longevity factor by maintaining proper transcriptional programs. Its role as a histone reader and transcriptional co-activator places it squarely within epigenetic regulation of gene expression relevant to aging.",
"confidence": 0.72,
"key_pathways": [
"H3K4 methylation via COMPASS/SET1 complex",
"RNA Pol II transcriptional regulation",
"Histone modification reading and chromatin remodeling"
],
"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 is internally contradictory - it correctly notes that loss of H3K4 methylation machinery (ash-2, set-2) extends lifespan, which would make WDR-5.1 (as part of the same complex) anti-longevity, not pro-longevity. The model then pivots to claim WDR-5.1 is \"required for longevity in certain contexts\" without strong justification, contradicting its own mechanistic reasoning. The correct conclusion from the model's own mechanistic description should have been anti_longevity (since WDR-5.1 promotes H3K4 methylation, and reducing H3K4 methylation extends lifespan). The model had the right mechanistic framework but drew the wrong conclusion, and did so with 0.72 confidence.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}