SFL1
S. cerevisiae
Sfl1p
What the model saw
Gene: SFL1 Organism: Saccharomyces cerevisiae Known functions: Sfl1p. DNA-binding transcription factor activity. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II-specific DNA-binding transcription factor binding. sequence-specific DNA binding.
View unredacted entry
Sfl1p. DNA-binding transcription factor activity. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II-specific DNA-binding transcription factor binding. sequence-specific DNA binding.
Solver output
SFL1 (Suppressor of Flocculation 1) is an RNA Pol II-specific transcription factor in S. cerevisiae that acts as a transcriptional repressor of flocculation genes (FLO1, FLO8) and is functionally linked to the cAMP-PKA nutrient sensing pathway. PKA phosphorylation inactivates Sfl1p, relieving repression of flocculation and stress-response genes; thus, active Sfl1p (under low PKA/nutrient-restricted conditions) promotes stress resistance and represses growth-promoting programs. Because high PKA activity (nutrient-rich, pro-aging state) inhibits Sfl1p, the normal function of Sfl1p as a transcriptional repressor of PKA targets aligns with dampening nutrient-sensing-driven growth, a configuration associated with extended lifespan in yeast. Additionally, Sfl1p has been reported to repress HSP90 (HSC82) expression, but its dominant role in opposing hyperactive PKA signaling places it on the pro-longevity side of the nutrient-sensing axis.
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 about SFL1's role in the cAMP-PKA pathway is partially accurate (SFL1 is indeed a transcriptional repressor regulated by PKA), but the model incorrectly inferred that this makes SFL1 pro-longevity. In reality, SFL1 is anti-longevity, meaning its deletion or loss of function extends lifespan. The model's logic that "opposing hyperactive PKA signaling = pro-longevity" is flawed in this context. SFL1 also represses FLO11 and other genes, and its deletion has been shown to extend chronological or replicative lifespan in yeast. The model's mechanistic reasoning about PKA pathway opposition was speculative and ultimately led to the wrong conclusion. The confidence of 0.55 is relatively low, but the model still committed to the wrong answer.
Raw API responses
solver
{
"reasoning": "SFL1 (Suppressor of Flocculation 1) is an RNA Pol II-specific transcription factor in S. cerevisiae that acts as a transcriptional repressor of flocculation genes (FLO1, FLO8) and is functionally linked to the cAMP-PKA nutrient sensing pathway. PKA phosphorylation inactivates Sfl1p, relieving repression of flocculation and stress-response genes; thus, active Sfl1p (under low PKA/nutrient-restricted conditions) promotes stress resistance and represses growth-promoting programs. Because high PKA activity (nutrient-rich, pro-aging state) inhibits Sfl1p, the normal function of Sfl1p as a transcriptional repressor of PKA targets aligns with dampening nutrient-sensing-driven growth, a configuration associated with extended lifespan in yeast. Additionally, Sfl1p has been reported to repress HSP90 (HSC82) expression, but its dominant role in opposing hyperactive PKA signaling places it on the pro-longevity side of the nutrient-sensing axis.",
"confidence": 0.55,
"key_pathways": [
"cAMP-PKA nutrient sensing pathway",
"FLO gene transcriptional repression",
"stress response transcriptional regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" The model's reasoning about SFL1's role in the cAMP-PKA pathway is partially accurate (SFL1 is indeed a transcriptional repressor regulated by PKA), but the model incorrectly inferred that this makes SFL1 pro-longevity. In reality, SFL1 is anti-longevity, meaning its deletion or loss of function extends lifespan. The model's logic that \"opposing hyperactive PKA signaling = pro-longevity\" is flawed in this context. SFL1 also represses FLO11 and other genes, and its deletion has been shown to extend chronological or replicative lifespan in yeast. The model's mechanistic reasoning about PKA pathway opposition was speculative and ultimately led to the wrong conclusion. The confidence of 0.55 is relatively low, but the model still committed to the wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}