npp-2
C. elegans
Nuclear pore complex protein Nup85
What the model saw
Gene: npp-2 Organism: Caenorhabditis elegans Known functions: Nuclear pore complex protein Nup85. structural constituent of nuclear pore.
View unredacted entry
Nuclear pore complex protein Nup85. structural constituent of nuclear pore.
Solver output
npp-2 encodes the C. elegans ortholog of Nup85, a structural component of the nuclear pore complex (NPC) Y-complex/Nup107-160 subcomplex. Proper NPC architecture is essential for maintaining nucleocytoplasmic transport fidelity, which safeguards nuclear integrity and genome stability. Age-related deterioration of NPC structure—particularly of long-lived scaffold nucleoporins—is a well-documented contributor to genomic instability and loss of nuclear compartmentalization in aging cells. By providing structural integrity to the NPC, npp-2 supports accurate mRNA export, nuclear import of DNA repair factors, and exclusion of cytoplasmic components from the nucleus, all of which collectively oppose age-associated genomic and proteomic decline. Loss of NPC integrity has been shown to accelerate aging phenotypes in C. elegans, suggesting that normal npp-2 function 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 correctly predicted pro_longevity for npp-2. The mechanistic reasoning is well-grounded: npp-2 encodes Nup85, a structural component of the NPC Y-complex, and the model correctly identifies that NPC integrity supports nucleocytoplasmic transport, genome stability, and nuclear compartmentalization — all relevant to aging. The reasoning about age-related NPC deterioration and its link to aging phenotypes in C. elegans is scientifically sound. Confidence of 0.62 is appropriately moderate given the indirect nature of the evidence. The mechanism class of "genomic_instability" is reasonable, though "nuclear transport/proteostasis" might be equally or more apt. Overall a strong, well-reasoned prediction.
Raw API responses
solver
{
"reasoning": "npp-2 encodes the C. elegans ortholog of Nup85, a structural component of the nuclear pore complex (NPC) Y-complex/Nup107-160 subcomplex. Proper NPC architecture is essential for maintaining nucleocytoplasmic transport fidelity, which safeguards nuclear integrity and genome stability. Age-related deterioration of NPC structure—particularly of long-lived scaffold nucleoporins—is a well-documented contributor to genomic instability and loss of nuclear compartmentalization in aging cells. By providing structural integrity to the NPC, npp-2 supports accurate mRNA export, nuclear import of DNA repair factors, and exclusion of cytoplasmic components from the nucleus, all of which collectively oppose age-associated genomic and proteomic decline. Loss of NPC integrity has been shown to accelerate aging phenotypes in C. elegans, suggesting that normal npp-2 function is pro-longevity.",
"confidence": 0.62,
"key_pathways": [
"nuclear pore complex assembly (Y-complex/Nup107-160)",
"nucleocytoplasmic transport",
"nuclear envelope integrity and genome stability"
],
"mechanism_class": "genomic_instability",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for npp-2. The mechanistic reasoning is well-grounded: npp-2 encodes Nup85, a structural component of the NPC Y-complex, and the model correctly identifies that NPC integrity supports nucleocytoplasmic transport, genome stability, and nuclear compartmentalization — all relevant to aging. The reasoning about age-related NPC deterioration and its link to aging phenotypes in C. elegans is scientifically sound. Confidence of 0.62 is appropriately moderate given the indirect nature of the evidence. The mechanism class of \"genomic_instability\" is reasonable, though \"nuclear transport/proteostasis\" might be equally or more apt. Overall a strong, well-reasoned prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}