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ndk1

S. pombe

nucleoside diphosphate kinase Ndk1

What the model saw

Gene: ndk1
Organism: Schizosaccharomyces pombe
Known functions: nucleoside diphosphate kinase Ndk1. nucleoside diphosphate kinase activity.
View unredacted entry
nucleoside diphosphate kinase Ndk1. nucleoside diphosphate kinase activity.

Solver output

Predicted influence
Pro-longevity
Confidence
62%
Mechanism
Other
Reasoning

Nucleoside diphosphate kinase (NDK/NME) catalyzes the transfer of phosphate groups from NTPs to NDPs, maintaining balanced nucleotide pools (dNTPs and NTPs) essential for DNA replication and repair. Adequate dNTP pools are critical for faithful genome duplication and DNA damage repair; imbalanced or depleted dNTP pools lead to replication stress, increased mutation rates, and genomic instability. In yeast and other model organisms, NME/NDK homologs have been linked to mitochondrial DNA maintenance and genome stability, both of which are central to longevity. Loss of ndk1 function would compromise nucleotide homeostasis, increasing genomic instability and potentially accelerating aging, suggesting the wild-type gene is pro-longevity.

Key pathways
nucleotide pool homeostasisDNA replication fidelity and repairmitochondrial DNA maintenance
Longevity influence
Anti-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
Incorrect
Mechanism
Incorrect
Reasoning quality
2/5
Failure mode
Confident wrong
Notes

The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumed that ndk1 loss would be harmful (implying the gene is pro-longevity), but in reality ndk1 is anti-longevity in S. pombe, meaning its deletion or loss likely extends lifespan. The mechanistic reasoning about nucleotide pool homeostasis and genome stability is plausible in general but leads to the wrong conclusion for this specific gene. The model had moderate confidence (0.62) but was still wrong on both the answer and the mechanism's directional implication.

Raw API responses

solver

{
  "reasoning": "Nucleoside diphosphate kinase (NDK/NME) catalyzes the transfer of phosphate groups from NTPs to NDPs, maintaining balanced nucleotide pools (dNTPs and NTPs) essential for DNA replication and repair. Adequate dNTP pools are critical for faithful genome duplication and DNA damage repair; imbalanced or depleted dNTP pools lead to replication stress, increased mutation rates, and genomic instability. In yeast and other model organisms, NME/NDK homologs have been linked to mitochondrial DNA maintenance and genome stability, both of which are central to longevity. Loss of ndk1 function would compromise nucleotide homeostasis, increasing genomic instability and potentially accelerating aging, suggesting the wild-type gene is pro-longevity.",
  "confidence": 0.62,
  "key_pathways": [
    "nucleotide pool homeostasis",
    "DNA replication fidelity and repair",
    "mitochondrial DNA maintenance"
  ],
  "mechanism_class": "other",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumed that ndk1 loss would be harmful (implying the gene is pro-longevity), but in reality ndk1 is anti-longevity in S. pombe, meaning its deletion or loss likely extends lifespan. The mechanistic reasoning about nucleotide pool homeostasis and genome stability is plausible in general but leads to the wrong conclusion for this specific gene. The model had moderate confidence (0.62) but was still wrong on both the answer and the mechanism's directional implication.",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}