SHM1
S. cerevisiae
glycine hydroxymethyltransferase SHM1
What the model saw
Gene: SHM1 Organism: Saccharomyces cerevisiae Known functions: glycine hydroxymethyltransferase SHM1. glycine hydroxymethyltransferase activity. pyridoxal phosphate binding.
View unredacted entry
glycine hydroxymethyltransferase SHM1. glycine hydroxymethyltransferase activity. pyridoxal phosphate binding.
Solver output
SHM1 encodes the mitochondrial isoform of serine hydroxymethyltransferase (SHMT) in S. cerevisiae, catalyzing the reversible interconversion of serine and glycine while transferring a one-carbon unit to tetrahydrofolate (THF), thereby generating 5,10-methylene-THF. This reaction is a central node in one-carbon (folate) metabolism, which feeds into nucleotide biosynthesis, methionine regeneration, and S-adenosylmethionine (SAM)-dependent methylation reactions. Adequate one-carbon flux supports epigenetic methylation marks and nucleotide pools required for DNA repair and replication fidelity, both of which are critical for genomic stability and healthy aging. The pyridoxal phosphate (PLP) cofactor dependence places SHM1 in the broader amino acid/one-carbon metabolic network that intersects with TOR and methionine-sensing pathways known to modulate yeast lifespan. Loss of mitochondrial SHMT activity can impair mitochondrial folate metabolism and nucleotide synthesis, potentially compromising mitochondrial genome integrity and overall cellular fitness, suggesting the normal function of SHM1 is pro-longevity.
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 is plausible on the surface (one-carbon metabolism, folate pathway, mitochondrial function), but it reaches the wrong conclusion. The model assumed that loss of SHM1 would be harmful (implying SHM1 is pro-longevity), when in fact SHM1 is anti-longevity in yeast, meaning its deletion or reduction likely extends lifespan. The model's confidence of 0.62 is moderate but still clearly wrong. The mechanistic reasoning about folate metabolism and mitochondrial nucleotide synthesis is not incorrect per se, but the interpretation of how this affects longevity is backwards. The model failed to consider that SHM1 activity could promote aging (e.g., by consuming glycine or affecting metabolic balance in ways that shorten lifespan), which is consistent with the anti-longevity classification.
Raw API responses
solver
{
"reasoning": "SHM1 encodes the mitochondrial isoform of serine hydroxymethyltransferase (SHMT) in S. cerevisiae, catalyzing the reversible interconversion of serine and glycine while transferring a one-carbon unit to tetrahydrofolate (THF), thereby generating 5,10-methylene-THF. This reaction is a central node in one-carbon (folate) metabolism, which feeds into nucleotide biosynthesis, methionine regeneration, and S-adenosylmethionine (SAM)-dependent methylation reactions. Adequate one-carbon flux supports epigenetic methylation marks and nucleotide pools required for DNA repair and replication fidelity, both of which are critical for genomic stability and healthy aging. The pyridoxal phosphate (PLP) cofactor dependence places SHM1 in the broader amino acid/one-carbon metabolic network that intersects with TOR and methionine-sensing pathways known to modulate yeast lifespan. Loss of mitochondrial SHMT activity can impair mitochondrial folate metabolism and nucleotide synthesis, potentially compromising mitochondrial genome integrity and overall cellular fitness, suggesting the normal function of SHM1 is pro-longevity.",
"confidence": 0.62,
"key_pathways": [
"one-carbon (folate) metabolism",
"serine-glycine interconversion and SAM-dependent methylation",
"mitochondrial nucleotide biosynthesis"
],
"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 is plausible on the surface (one-carbon metabolism, folate pathway, mitochondrial function), but it reaches the wrong conclusion. The model assumed that loss of SHM1 would be harmful (implying SHM1 is pro-longevity), when in fact SHM1 is anti-longevity in yeast, meaning its deletion or reduction likely extends lifespan. The model's confidence of 0.62 is moderate but still clearly wrong. The mechanistic reasoning about folate metabolism and mitochondrial nucleotide synthesis is not incorrect per se, but the interpretation of how this affects longevity is backwards. The model failed to consider that SHM1 activity could promote aging (e.g., by consuming glycine or affecting metabolic balance in ways that shorten lifespan), which is consistent with the anti-longevity classification.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}