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mml-1

C. elegans

BHLH domain-containing protein;Protein WBSCR14 homolog

What the model saw

Gene: mml-1
Organism: Caenorhabditis elegans
Known functions: BHLH domain-containing protein;Protein WBSCR14 homolog. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. protein binding. protein dimerization activity.
View unredacted entry
BHLH domain-containing protein;Protein WBSCR14 homolog. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. protein binding. protein dimerization activity.

Solver output

Predicted influence
Pro-longevity
Confidence
72%
Mechanism
Deregulated nutrient sensing
Reasoning

mml-1 is the C. elegans homolog of MondoA/WBSCR14 (MXL-3 partner), a bHLH-Zip transcription factor that heterodimerizes with its partner to bind carbohydrate response elements (ChoREs) and regulate glucose/nutrient-sensing transcriptional programs. In C. elegans, MML-1 functions as part of the MML-1/MXL-3 complex that acts downstream of TORC1 and in parallel with AMPK/AAK-2 to regulate metabolic gene expression. Loss of mml-1 has been shown to reduce lifespan or impair the transcriptional response to nutrient restriction, while its activity is required for the full pro-longevity effects of dietary restriction and reduced insulin/IGF-1 signaling. As a nutrient-sensing transcription factor that couples glucose availability to downstream metabolic gene regulation via RNA Pol II-specific DNA binding and protein dimerization, its normal function supports metabolic homeostasis and longevity.

Key pathways
MondoA/ChREBP nutrient-sensing transcriptionTORC1-MML-1 metabolic axisDietary restriction longevity pathway
Longevity influence
Pro-longevity
Lifespan effect
Decrease

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

Answer
Correct
Mechanism
Correct
Reasoning quality
4/5
Failure mode
Correct
Notes

The model correctly predicted mml-1 as pro_longevity with good confidence (0.72). The mechanistic reasoning is largely accurate - mml-1 encodes the C. elegans MondoA/ChREBP homolog (WBSCR14 homolog), which functions as a bHLH transcription factor involved in nutrient sensing. The model correctly identifies its role in the TORC1-MML-1 axis and dietary restriction pathways. The reasoning about MML-1/MXL-3 complex and its role in metabolic gene regulation is consistent with published C. elegans literature. The model correctly notes that mml-1 activity is required for pro-longevity effects, supporting its classification as pro_longevity. Minor uncertainty exists about some specific details (e.g., whether loss of mml-1 reduces lifespan or whether it's overexpression that extends lifespan), but the overall mechanistic framework is sound.

Raw API responses

solver

{
  "reasoning": "mml-1 is the C. elegans homolog of MondoA/WBSCR14 (MXL-3 partner), a bHLH-Zip transcription factor that heterodimerizes with its partner to bind carbohydrate response elements (ChoREs) and regulate glucose/nutrient-sensing transcriptional programs. In C. elegans, MML-1 functions as part of the MML-1/MXL-3 complex that acts downstream of TORC1 and in parallel with AMPK/AAK-2 to regulate metabolic gene expression. Loss of mml-1 has been shown to reduce lifespan or impair the transcriptional response to nutrient restriction, while its activity is required for the full pro-longevity effects of dietary restriction and reduced insulin/IGF-1 signaling. As a nutrient-sensing transcription factor that couples glucose availability to downstream metabolic gene regulation via RNA Pol II-specific DNA binding and protein dimerization, its normal function supports metabolic homeostasis and longevity.",
  "confidence": 0.72,
  "key_pathways": [
    "MondoA/ChREBP nutrient-sensing transcription",
    "TORC1-MML-1 metabolic axis",
    "Dietary restriction longevity pathway"
  ],
  "mechanism_class": "deregulated_nutrient_sensing",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model correctly predicted mml-1 as pro_longevity with good confidence (0.72). The mechanistic reasoning is largely accurate - mml-1 encodes the C. elegans MondoA/ChREBP homolog (WBSCR14 homolog), which functions as a bHLH transcription factor involved in nutrient sensing. The model correctly identifies its role in the TORC1-MML-1 axis and dietary restriction pathways. The reasoning about MML-1/MXL-3 complex and its role in metabolic gene regulation is consistent with published C. elegans literature. The model correctly notes that mml-1 activity is required for pro-longevity effects, supporting its classification as pro_longevity. Minor uncertainty exists about some specific details (e.g., whether loss of mml-1 reduces lifespan or whether it's overexpression that extends lifespan), but the overall mechanistic framework is sound.",
  "failure_mode": "correct",
  "answer_correct": true,
  "mechanism_correct": true,
  "reasoning_quality": 4,
  "ground_truth_questionable": false
}