GLN3
S. cerevisiae
nitrogen-responsive transcriptional regulator GLN3
What the model saw
Gene: GLN3 Organism: Saccharomyces cerevisiae Known functions: nitrogen-responsive transcriptional regulator GLN3. DNA-binding transcription factor activity. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. protein binding. sequence-specific DNA binding. zinc ion binding.
View unredacted entry
nitrogen-responsive transcriptional regulator GLN3. DNA-binding transcription factor activity. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. protein binding. sequence-specific DNA binding. zinc ion binding.
Solver output
GLN3 is a GATA-type zinc finger transcription factor that serves as the primary transcriptional activator of nitrogen catabolite repression (NCR) target genes in yeast. Under nitrogen-rich conditions, GLN3 is sequestered in the cytoplasm via TORC1-mediated phosphorylation (through Ure2), keeping NCR genes repressed. When nitrogen is limiting or TORC1 is inhibited (e.g., by rapamycin), GLN3 translocates to the nucleus and activates genes involved in scavenging alternative nitrogen sources. Because GLN3 activation is a downstream consequence of TORC1 inhibition — the same pathway that mediates lifespan extension by rapamycin and dietary restriction — GLN3 nuclear activity is functionally coupled to the pro-longevity state of reduced TOR signaling. Loss of GLN3 partially suppresses the lifespan extension conferred by TORC1 inhibition, indicating that GLN3-driven transcription contributes to the longevity benefit of attenuated nutrient sensing. Thus, GLN3's normal function as a nitrogen-limitation-responsive activator aligns it with the pro-longevity arm of the TOR/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 GLN3 as pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — GLN3 is indeed a downstream effector of TORC1 inhibition — but it gets the directionality wrong. In yeast, GLN3 deletion (loss of function) tends to extend lifespan, meaning GLN3's normal activity is anti-longevity. The model incorrectly argues that GLN3 activation is part of the pro-longevity response to TORC1 inhibition, when in fact GLN3 appears to promote aging (its deletion extends lifespan). The claim that "loss of GLN3 partially suppresses lifespan extension conferred by TORC1 inhibition" is presented as supporting pro-longevity, but the actual data in the literature suggests GLN3 deletion itself extends lifespan, making it anti-longevity. The mechanistic framing conflates being downstream of a pro-longevity pathway with being pro-longevity itself — a logical error. The reasoning quality is poor because it reaches a confident wrong conclusion through flawed logic despite correctly identifying the relevant pathway.
Raw API responses
solver
{
"reasoning": "GLN3 is a GATA-type zinc finger transcription factor that serves as the primary transcriptional activator of nitrogen catabolite repression (NCR) target genes in yeast. Under nitrogen-rich conditions, GLN3 is sequestered in the cytoplasm via TORC1-mediated phosphorylation (through Ure2), keeping NCR genes repressed. When nitrogen is limiting or TORC1 is inhibited (e.g., by rapamycin), GLN3 translocates to the nucleus and activates genes involved in scavenging alternative nitrogen sources. Because GLN3 activation is a downstream consequence of TORC1 inhibition — the same pathway that mediates lifespan extension by rapamycin and dietary restriction — GLN3 nuclear activity is functionally coupled to the pro-longevity state of reduced TOR signaling. Loss of GLN3 partially suppresses the lifespan extension conferred by TORC1 inhibition, indicating that GLN3-driven transcription contributes to the longevity benefit of attenuated nutrient sensing. Thus, GLN3's normal function as a nitrogen-limitation-responsive activator aligns it with the pro-longevity arm of the TOR/nutrient-sensing axis.",
"confidence": 0.72,
"key_pathways": [
"TOR/TORC1 nitrogen catabolite repression (NCR)",
"GATA transcription factor / GLN3-Ure2 signaling",
"dietary restriction / nitrogen limitation response"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted GLN3 as pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — GLN3 is indeed a downstream effector of TORC1 inhibition — but it gets the directionality wrong. In yeast, GLN3 deletion (loss of function) tends to extend lifespan, meaning GLN3's normal activity is anti-longevity. The model incorrectly argues that GLN3 activation is part of the pro-longevity response to TORC1 inhibition, when in fact GLN3 appears to promote aging (its deletion extends lifespan). The claim that \"loss of GLN3 partially suppresses lifespan extension conferred by TORC1 inhibition\" is presented as supporting pro-longevity, but the actual data in the literature suggests GLN3 deletion itself extends lifespan, making it anti-longevity. The mechanistic framing conflates being downstream of a pro-longevity pathway with being pro-longevity itself — a logical error. The reasoning quality is poor because it reaches a confident wrong conclusion through flawed logic despite correctly identifying the relevant pathway.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}