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ndk-1

C. elegans

Nucleoside diphosphate kinase

What the model saw

Gene: ndk-1
Organism: Caenorhabditis elegans
Known functions: Nucleoside diphosphate kinase. identical protein binding. nucleoside diphosphate kinase activity. protein binding. protein histidine kinase activity.
View unredacted entry
Nucleoside diphosphate kinase. identical protein binding. nucleoside diphosphate kinase activity. protein binding. protein histidine kinase activity.

Solver output

Predicted influence
Pro-longevity
Confidence
62%
Mechanism
Other
Reasoning

NDK-1 is the C. elegans nucleoside diphosphate kinase (NDPK/NME), which catalyzes the transfer of phosphate groups between nucleoside diphosphates and triphosphates, maintaining balanced NTP pools essential for DNA replication, RNA synthesis, and energy metabolism. In multiple organisms, NDPK/NME family members have been shown to support mitochondrial function and genome integrity by ensuring adequate dNTP and NTP supply. The protein histidine kinase activity of NDK-1 is also notable: in C. elegans, ndk-1 has been linked to the KSR-1 (kinase suppressor of Ras) signaling axis and modulation of the RAS/MAPK pathway, where loss of ndk-1 suppresses Ras-mediated signaling. Since hyperactive Ras/MAPK signaling is generally detrimental to longevity, the normal function of NDK-1 in tempering this pathway—combined with its role in nucleotide homeostasis supporting mitochondrial and genomic integrity—suggests a net pro-longevity role.

Key pathways
nucleotide homeostasis / NTP pool maintenanceRAS/MAPK signaling modulation via protein histidine kinase activitymitochondrial nucleotide supply and energy metabolism
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 while the ground truth is anti_longevity. The model's reasoning about NDK-1's role in nucleotide homeostasis and RAS/MAPK signaling is plausible in general terms but leads to the wrong conclusion. The model incorrectly reasoned that because NDK-1 might temper Ras/MAPK signaling, it would be pro-longevity. In reality, ndk-1 in C. elegans is anti-longevity, meaning its loss or reduction extends lifespan. The model's confidence of 0.62 is moderate but still committed to the wrong answer. The mechanistic reasoning is also incorrect in its conclusion - if NDK-1 suppresses Ras signaling and Ras is detrimental to longevity, then NDK-1 would actually be anti-longevity (promoting aging) by suppressing a pathway that, when active, reduces lifespan - but the model's logic was internally inconsistent here as well.

Raw API responses

solver

{
  "reasoning": "NDK-1 is the C. elegans nucleoside diphosphate kinase (NDPK/NME), which catalyzes the transfer of phosphate groups between nucleoside diphosphates and triphosphates, maintaining balanced NTP pools essential for DNA replication, RNA synthesis, and energy metabolism. In multiple organisms, NDPK/NME family members have been shown to support mitochondrial function and genome integrity by ensuring adequate dNTP and NTP supply. The protein histidine kinase activity of NDK-1 is also notable: in C. elegans, ndk-1 has been linked to the KSR-1 (kinase suppressor of Ras) signaling axis and modulation of the RAS/MAPK pathway, where loss of ndk-1 suppresses Ras-mediated signaling. Since hyperactive Ras/MAPK signaling is generally detrimental to longevity, the normal function of NDK-1 in tempering this pathway—combined with its role in nucleotide homeostasis supporting mitochondrial and genomic integrity—suggests a net pro-longevity role.",
  "confidence": 0.62,
  "key_pathways": [
    "nucleotide homeostasis / NTP pool maintenance",
    "RAS/MAPK signaling modulation via protein histidine kinase activity",
    "mitochondrial nucleotide supply and energy metabolism"
  ],
  "mechanism_class": "other",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model predicted pro_longevity while the ground truth is anti_longevity. The model's reasoning about NDK-1's role in nucleotide homeostasis and RAS/MAPK signaling is plausible in general terms but leads to the wrong conclusion. The model incorrectly reasoned that because NDK-1 might temper Ras/MAPK signaling, it would be pro-longevity. In reality, ndk-1 in C. elegans is anti-longevity, meaning its loss or reduction extends lifespan. The model's confidence of 0.62 is moderate but still committed to the wrong answer. The mechanistic reasoning is also incorrect in its conclusion - if NDK-1 suppresses Ras signaling and Ras is detrimental to longevity, then NDK-1 would actually be anti-longevity (promoting aging) by suppressing a pathway that, when active, reduces lifespan - but the model's logic was internally inconsistent here as well.",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}