Nudt1
M. musculus
nudix hydrolase 1
What the model saw
Gene: NUDT1 Organism: Mus musculus Known functions: nudix hydrolase 1. oxidized purine nucleoside triphosphate hydrolase. 2-hydroxy-ATP hydrolase activity. 2-hydroxy-dATP hydrolase activity. 5'-(N(7)-methylguanosine 5'-triphospho)-[mRNA] hydrolase activity. 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity. 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity. ATP diphosphatase activity. N6-methyl-(d)ATP hydrolase activity. O6-methyl-dGTP hydrolase activity. dATP diphosphatase activity. hydrolase activity. hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides. protein binding. snoRNA binding.
View unredacted entry
nudix hydrolase 1. oxidized purine nucleoside triphosphate hydrolase. 2-hydroxy-ATP hydrolase activity. 2-hydroxy-dATP hydrolase activity. 5'-(N(7)-methylguanosine 5'-triphospho)-[mRNA] hydrolase activity. 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity. 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity. ATP diphosphatase activity. N6-methyl-(d)ATP hydrolase activity. O6-methyl-dGTP hydrolase activity. dATP diphosphatase activity. hydrolase activity. hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides. protein binding. snoRNA binding.
Solver output
NUDT1 (also known as MTH1) is a nudix hydrolase that sanitizes the oxidized nucleotide pool by hydrolyzing 8-oxo-dGTP, 8-oxo-GTP, 2-hydroxy-dATP, and other oxidatively damaged nucleoside triphosphates before they can be incorporated into DNA or RNA. By preventing misincorporation of oxidized purines (particularly 8-oxo-dGTP, which causes G:C→T:A transversions), NUDT1 directly suppresses oxidative stress-driven mutagenesis and genomic instability. This nucleotide pool sanitization function is a frontline defense against reactive oxygen species-induced DNA damage accumulation, a key driver of aging. Loss of this activity leads to elevated mutation rates and accelerated cellular dysfunction, consistent with a pro-longevity role for the wild-type gene. The mechanism maps squarely to the genomic instability hallmark of aging via the oxidized nucleotide pool surveillance pathway.
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 correctly predicted pro_longevity for NUDT1/MTH1 in Mus musculus. The mechanistic reasoning is excellent and accurate: NUDT1 sanitizes the oxidized nucleotide pool by hydrolyzing 8-oxo-dGTP and other damaged nucleotides, preventing their incorporation into DNA/RNA, thereby reducing oxidative stress-driven mutagenesis and genomic instability. This is a well-established function of MTH1/NUDT1. The model correctly identified the genomic instability hallmark of aging as the relevant mechanism, and the confidence level of 0.85 is appropriate. All key pathways listed are accurate and relevant.
Raw API responses
solver
{
"reasoning": "NUDT1 (also known as MTH1) is a nudix hydrolase that sanitizes the oxidized nucleotide pool by hydrolyzing 8-oxo-dGTP, 8-oxo-GTP, 2-hydroxy-dATP, and other oxidatively damaged nucleoside triphosphates before they can be incorporated into DNA or RNA. By preventing misincorporation of oxidized purines (particularly 8-oxo-dGTP, which causes G:C→T:A transversions), NUDT1 directly suppresses oxidative stress-driven mutagenesis and genomic instability. This nucleotide pool sanitization function is a frontline defense against reactive oxygen species-induced DNA damage accumulation, a key driver of aging. Loss of this activity leads to elevated mutation rates and accelerated cellular dysfunction, consistent with a pro-longevity role for the wild-type gene. The mechanism maps squarely to the genomic instability hallmark of aging via the oxidized nucleotide pool surveillance pathway.",
"confidence": 0.85,
"key_pathways": [
"oxidized nucleotide pool sanitization (8-oxo-dGTP hydrolysis)",
"reactive oxygen species-induced mutagenesis prevention",
"DNA damage avoidance via nucleotide quality control"
],
"mechanism_class": "genomic_instability",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for NUDT1/MTH1 in Mus musculus. The mechanistic reasoning is excellent and accurate: NUDT1 sanitizes the oxidized nucleotide pool by hydrolyzing 8-oxo-dGTP and other damaged nucleotides, preventing their incorporation into DNA/RNA, thereby reducing oxidative stress-driven mutagenesis and genomic instability. This is a well-established function of MTH1/NUDT1. The model correctly identified the genomic instability hallmark of aging as the relevant mechanism, and the confidence level of 0.85 is appropriate. All key pathways listed are accurate and relevant.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}