php2
S. pombe
CCAAT-binding factor complex subunit Php2
What the model saw
Gene: php2 Organism: Schizosaccharomyces pombe Known functions: CCAAT-binding factor complex subunit Php2. DNA binding. DNA-binding transcription activator activity, RNA polymerase II-specific. DNA-binding transcription factor activity. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II core promoter sequence-specific DNA binding. promoter-enhancer loop anchoring activity. sequence-specific DNA binding.
View unredacted entry
CCAAT-binding factor complex subunit Php2. DNA binding. DNA-binding transcription activator activity, RNA polymerase II-specific. DNA-binding transcription factor activity. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II core promoter sequence-specific DNA binding. promoter-enhancer loop anchoring activity. sequence-specific DNA binding.
Solver output
Php2 is the large subunit of the CCAAT-binding factor (CBF/NF-Y) complex in S. pombe, which binds CCAAT box elements in gene promoters to activate transcription via RNA Pol II. The NF-Y/CBF complex is a conserved master regulator of stress response, metabolic, and cell cycle genes; in yeast, the Php2/3/5 complex activates genes involved in mitochondrial respiration, iron-sulfur cluster assembly, and oxidative stress defense. By driving transcription of respiratory and antioxidant genes, Php2 supports mitochondrial function and proteostasis, both of which are critical for longevity. Loss of Php2 function leads to respiratory deficiency and impaired adaptation to nutrient and oxidative stress, conditions that shorten lifespan. The promoter-enhancer loop anchoring activity further suggests a role in maintaining proper chromatin architecture for gene expression programs that sustain cellular health.
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 Php2 activating respiratory and antioxidant genes sounds plausible on the surface, but it leads to the wrong conclusion. If php2 is anti_longevity, deletion or loss of php2 likely extends lifespan, meaning the gene's activity shortens lifespan rather than supporting it. The model's mechanistic framing (that loss of Php2 shortens lifespan) is directly contradicted by the ground truth. The model assigned moderate confidence (0.65) but still got the direction wrong. The mechanism class of 'epigenetic_alterations' is also questionable for a transcription factor complex subunit - it would more accurately be classified as a transcriptional regulation mechanism.
Raw API responses
solver
{
"reasoning": "Php2 is the large subunit of the CCAAT-binding factor (CBF/NF-Y) complex in S. pombe, which binds CCAAT box elements in gene promoters to activate transcription via RNA Pol II. The NF-Y/CBF complex is a conserved master regulator of stress response, metabolic, and cell cycle genes; in yeast, the Php2/3/5 complex activates genes involved in mitochondrial respiration, iron-sulfur cluster assembly, and oxidative stress defense. By driving transcription of respiratory and antioxidant genes, Php2 supports mitochondrial function and proteostasis, both of which are critical for longevity. Loss of Php2 function leads to respiratory deficiency and impaired adaptation to nutrient and oxidative stress, conditions that shorten lifespan. The promoter-enhancer loop anchoring activity further suggests a role in maintaining proper chromatin architecture for gene expression programs that sustain cellular health.",
"confidence": 0.65,
"key_pathways": [
"CCAAT-binding factor (CBF/NF-Y) transcriptional activation",
"mitochondrial respiratory gene regulation",
"oxidative stress response transcription"
],
"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 about Php2 activating respiratory and antioxidant genes sounds plausible on the surface, but it leads to the wrong conclusion. If php2 is anti_longevity, deletion or loss of php2 likely extends lifespan, meaning the gene's activity shortens lifespan rather than supporting it. The model's mechanistic framing (that loss of Php2 shortens lifespan) is directly contradicted by the ground truth. The model assigned moderate confidence (0.65) but still got the direction wrong. The mechanism class of 'epigenetic_alterations' is also questionable for a transcription factor complex subunit - it would more accurately be classified as a transcriptional regulation mechanism.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}