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Gnmt

D. melanogaster

Glycine N-methyltransferase

What the model saw

Gene: Gnmt
Organism: Drosophila melanogaster
Known functions: Glycine N-methyltransferase. glycine N-methyltransferase. S-adenosyl-L-methionine binding. glycine N-methyltransferase activity. glycine binding. identical protein binding.
View unredacted entry
Glycine N-methyltransferase. glycine N-methyltransferase. S-adenosyl-L-methionine binding. glycine N-methyltransferase activity. glycine binding. identical protein binding.

Solver output

Predicted influence
Pro-longevity
Confidence
82%
Mechanism
Deregulated nutrient sensing
Reasoning

Glycine N-methyltransferase (GNMT) catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to glycine, producing sarcosine and S-adenosyl-L-homocysteine (SAH). This reaction is a major regulator of the SAM:SAH ratio and one-carbon metabolism, effectively acting as a metabolic rheostat for methyl group availability. In Drosophila, Gnmt has been shown to extend lifespan by modulating SAM levels; excess SAM is associated with reduced longevity, and GNMT activity depletes SAM, thereby limiting aberrant methylation reactions. This connects directly to nutrient-sensing pathways, as SAM is a key metabolic sensor linking dietary methionine intake to downstream signaling (including mTORC1 activation). By buffering SAM levels, GNMT dampens nutrient-sensing pathway activity, mimicking the pro-longevity effects of methionine restriction.

Key pathways
S-adenosylmethionine (SAM) metabolism / one-carbon metabolismMethionine restriction / mTORC1 nutrient sensingMethylation homeostasis
Longevity influence
Pro-longevity
Lifespan effect
Increase

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
5/5
Failure mode
Correct
Notes

The model correctly predicted pro_longevity for Gnmt in Drosophila melanogaster with high confidence (0.82). The mechanistic reasoning is excellent and accurate: GNMT depletes SAM, which buffers one-carbon metabolism and limits aberrant methylation, connecting to methionine restriction and mTORC1/nutrient sensing pathways. This aligns well with published literature on Gnmt in Drosophila longevity. The mechanism classification as "deregulated_nutrient_sensing" is appropriate given the SAM-mTORC1 connection.

Raw API responses

solver

{
  "reasoning": "Glycine N-methyltransferase (GNMT) catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to glycine, producing sarcosine and S-adenosyl-L-homocysteine (SAH). This reaction is a major regulator of the SAM:SAH ratio and one-carbon metabolism, effectively acting as a metabolic rheostat for methyl group availability. In Drosophila, Gnmt has been shown to extend lifespan by modulating SAM levels; excess SAM is associated with reduced longevity, and GNMT activity depletes SAM, thereby limiting aberrant methylation reactions. This connects directly to nutrient-sensing pathways, as SAM is a key metabolic sensor linking dietary methionine intake to downstream signaling (including mTORC1 activation). By buffering SAM levels, GNMT dampens nutrient-sensing pathway activity, mimicking the pro-longevity effects of methionine restriction.",
  "confidence": 0.82,
  "key_pathways": [
    "S-adenosylmethionine (SAM) metabolism / one-carbon metabolism",
    "Methionine restriction / mTORC1 nutrient sensing",
    "Methylation homeostasis"
  ],
  "mechanism_class": "deregulated_nutrient_sensing",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model correctly predicted pro_longevity for Gnmt in Drosophila melanogaster with high confidence (0.82). The mechanistic reasoning is excellent and accurate: GNMT depletes SAM, which buffers one-carbon metabolism and limits aberrant methylation, connecting to methionine restriction and mTORC1/nutrient sensing pathways. This aligns well with published literature on Gnmt in Drosophila longevity. The mechanism classification as \"deregulated_nutrient_sensing\" is appropriate given the SAM-mTORC1 connection.",
  "failure_mode": "correct",
  "answer_correct": true,
  "mechanism_correct": true,
  "reasoning_quality": 5,
  "ground_truth_questionable": false
}