MTD1
S. cerevisiae
methylenetetrahydrofolate dehydrogenase (NAD(+))
What the model saw
Gene: MTD1 Organism: Saccharomyces cerevisiae Known functions: methylenetetrahydrofolate dehydrogenase (NAD(+)). methylenetetrahydrofolate dehydrogenase (NAD+) activity. methylenetetrahydrofolate dehydrogenase (NADP+) activity.
View unredacted entry
methylenetetrahydrofolate dehydrogenase (NAD(+)). methylenetetrahydrofolate dehydrogenase (NAD+) activity. methylenetetrahydrofolate dehydrogenase (NADP+) activity.
Solver output
MTD1 encodes a mitochondrial methylenetetrahydrofolate dehydrogenase that catalyzes the interconversion of 5,10-methyleneTHF to 5,10-methenylTHF using NAD(+) (and NADP+) as cofactor. This reaction is a central step in one-carbon (folate) metabolism, which feeds into the methionine cycle and ultimately governs S-adenosylmethionine (SAM) availability. SAM is the universal methyl donor for DNA, RNA, and histone methylation reactions. Adequate flux through this pathway supports proper epigenetic methylation marks and nucleotide biosynthesis, both of which are critical for genome integrity and cellular homeostasis. In yeast, disruption of mitochondrial one-carbon metabolism impairs SAM-dependent methylation and has been linked to reduced chronological and replicative lifespan, suggesting that normal MTD1 function supports longevity by sustaining methyl-group supply for epigenetic regulation.
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. MTD1 is an anti-longevity gene in yeast, meaning its deletion or loss extends lifespan. The model's reasoning constructed a plausible-sounding but ultimately incorrect narrative about MTD1 supporting longevity through one-carbon metabolism and SAM-dependent epigenetic methylation. The mechanism class of "epigenetic_alterations" is speculative and not well-supported. The model's confidence of 0.62 is moderate but still wrong. The reasoning quality is low because it fabricated a directional conclusion ("disruption impairs lifespan") that contradicts the actual experimental evidence, and the mechanistic framing around epigenetic methylation is not well-grounded for this specific gene.
Raw API responses
solver
{
"reasoning": "MTD1 encodes a mitochondrial methylenetetrahydrofolate dehydrogenase that catalyzes the interconversion of 5,10-methyleneTHF to 5,10-methenylTHF using NAD(+) (and NADP+) as cofactor. This reaction is a central step in one-carbon (folate) metabolism, which feeds into the methionine cycle and ultimately governs S-adenosylmethionine (SAM) availability. SAM is the universal methyl donor for DNA, RNA, and histone methylation reactions. Adequate flux through this pathway supports proper epigenetic methylation marks and nucleotide biosynthesis, both of which are critical for genome integrity and cellular homeostasis. In yeast, disruption of mitochondrial one-carbon metabolism impairs SAM-dependent methylation and has been linked to reduced chronological and replicative lifespan, suggesting that normal MTD1 function supports longevity by sustaining methyl-group supply for epigenetic regulation.",
"confidence": 0.62,
"key_pathways": [
"one-carbon (folate) metabolism",
"methionine/SAM cycle",
"epigenetic methylation"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. MTD1 is an anti-longevity gene in yeast, meaning its deletion or loss extends lifespan. The model's reasoning constructed a plausible-sounding but ultimately incorrect narrative about MTD1 supporting longevity through one-carbon metabolism and SAM-dependent epigenetic methylation. The mechanism class of \"epigenetic_alterations\" is speculative and not well-supported. The model's confidence of 0.62 is moderate but still wrong. The reasoning quality is low because it fabricated a directional conclusion (\"disruption impairs lifespan\") that contradicts the actual experimental evidence, and the mechanistic framing around epigenetic methylation is not well-grounded for this specific gene.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}