mdl-1
C. elegans
Mad-like protein 1
What the model saw
Gene: mdl-1 Organism: Caenorhabditis elegans Known functions: Mad-like protein 1. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. protein binding. protein dimerization activity. protein heterodimerization activity. sequence-specific DNA binding.
View unredacted entry
Mad-like protein 1. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. protein binding. protein dimerization activity. protein heterodimerization activity. sequence-specific DNA binding.
Solver output
MDL-1 is the C. elegans ortholog of mammalian Mad/MXD proteins, which are transcriptional repressors that heterodimerize with Max and antagonize Myc-driven transcriptional programs. In C. elegans, mdl-1 functions downstream of the TORC1/TOR signaling pathway and acts as a transcription factor that represses Myc-Max (MML-1/MDL-1 complex) target genes involved in growth and metabolism. Loss of mdl-1 has been shown to suppress lifespan extension in contexts such as dietary restriction and reduced insulin/IGF-1 signaling, indicating that MDL-1 activity is required for longevity. By heterodimerizing with MAX-like proteins and binding RNA Pol II-regulated promoters, MDL-1 represses pro-growth, pro-aging transcriptional programs, thereby promoting longevity through modulation of nutrient-sensing (TOR/Myc axis) transcriptional output.
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 contains a key error: it claims that loss of mdl-1 suppresses lifespan extension, implying MDL-1 is required for longevity (pro_longevity). However, the actual finding in the literature is that mdl-1 is anti-longevity — meaning its loss or reduction tends to extend lifespan, not shorten it. The model correctly identifies MDL-1 as a Mad-like transcriptional repressor that heterodimerizes with Max and antagonizes Myc-driven programs, and correctly notes the MML-1/MDL-1 complex and TOR/Myc axis involvement. However, it misinterprets the directionality of mdl-1's effect on lifespan. The model confuses the roles of mml-1 (pro_longevity) and mdl-1 (anti_longevity) in the MML-1:MDL-1 complex. MDL-1 acts as a repressor of MML-1 target genes that promote longevity, making it anti-longevity. The model had moderate-high confidence (0.72) in the wrong answer.
Raw API responses
solver
{
"reasoning": "MDL-1 is the C. elegans ortholog of mammalian Mad/MXD proteins, which are transcriptional repressors that heterodimerize with Max and antagonize Myc-driven transcriptional programs. In C. elegans, mdl-1 functions downstream of the TORC1/TOR signaling pathway and acts as a transcription factor that represses Myc-Max (MML-1/MDL-1 complex) target genes involved in growth and metabolism. Loss of mdl-1 has been shown to suppress lifespan extension in contexts such as dietary restriction and reduced insulin/IGF-1 signaling, indicating that MDL-1 activity is required for longevity. By heterodimerizing with MAX-like proteins and binding RNA Pol II-regulated promoters, MDL-1 represses pro-growth, pro-aging transcriptional programs, thereby promoting longevity through modulation of nutrient-sensing (TOR/Myc axis) transcriptional output.",
"confidence": 0.72,
"key_pathways": [
"TOR/Myc transcriptional axis (MML-1:MDL-1 complex)",
"Insulin/IGF-1 signaling longevity pathway",
"Dietary restriction transcriptional response"
],
"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 contains a key error: it claims that loss of mdl-1 suppresses lifespan extension, implying MDL-1 is required for longevity (pro_longevity). However, the actual finding in the literature is that mdl-1 is anti-longevity — meaning its loss or reduction tends to extend lifespan, not shorten it. The model correctly identifies MDL-1 as a Mad-like transcriptional repressor that heterodimerizes with Max and antagonizes Myc-driven programs, and correctly notes the MML-1/MDL-1 complex and TOR/Myc axis involvement. However, it misinterprets the directionality of mdl-1's effect on lifespan. The model confuses the roles of mml-1 (pro_longevity) and mdl-1 (anti_longevity) in the MML-1:MDL-1 complex. MDL-1 acts as a repressor of MML-1 target genes that promote longevity, making it anti-longevity. The model had moderate-high confidence (0.72) in the wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}