icd-2
C. elegans
Nascent polypeptide-associated complex subunit alpha
What the model saw
Gene: icd-2 Organism: Caenorhabditis elegans Known functions: Nascent polypeptide-associated complex subunit alpha. protein binding. unfolded protein binding.
View unredacted entry
Nascent polypeptide-associated complex subunit alpha. protein binding. unfolded protein binding.
Solver output
ICD-2 is the alpha subunit of the Nascent Polypeptide-Associated Complex (NAC), a ribosome-associated chaperone that binds unfolded/nascent polypeptides co-translationally to prevent misfolding and aggregation. By engaging newly synthesized proteins at the ribosome exit tunnel, NAC acts as a first-line proteostasis factor that promotes correct folding and prevents aberrant protein aggregation. In C. elegans, NAC subunits (including the alpha subunit) have been shown to support proteostasis networks that are critical for healthy aging; loss of NAC function leads to increased protein aggregation and reduced lifespan. The unfolded protein binding activity directly links this gene to the maintenance of proteostasis, a key hallmark of aging. Therefore, the normal function of icd-2 is expected to oppose proteotoxic stress and support 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 about NAC being a proteostasis factor that supports longevity is plausible in general terms, but it is factually incorrect for icd-2 in C. elegans. In reality, icd-2/NAC-alpha has been shown to have anti-longevity effects - its loss or reduction actually extends lifespan rather than shortening it. The model confidently asserted that "loss of NAC function leads to increased protein aggregation and reduced lifespan," which is the opposite of what the GenAge database records. The model's mechanistic framework (NAC as proteostasis factor) is reasonable in principle but leads to the wrong conclusion for this specific gene. The model showed moderate confidence (0.65) but was still clearly wrong on both the answer and the mechanism's directional effect.
Raw API responses
solver
{
"reasoning": "ICD-2 is the alpha subunit of the Nascent Polypeptide-Associated Complex (NAC), a ribosome-associated chaperone that binds unfolded/nascent polypeptides co-translationally to prevent misfolding and aggregation. By engaging newly synthesized proteins at the ribosome exit tunnel, NAC acts as a first-line proteostasis factor that promotes correct folding and prevents aberrant protein aggregation. In C. elegans, NAC subunits (including the alpha subunit) have been shown to support proteostasis networks that are critical for healthy aging; loss of NAC function leads to increased protein aggregation and reduced lifespan. The unfolded protein binding activity directly links this gene to the maintenance of proteostasis, a key hallmark of aging. Therefore, the normal function of icd-2 is expected to oppose proteotoxic stress and support longevity.",
"confidence": 0.65,
"key_pathways": [
"nascent polypeptide-associated complex (NAC) chaperone activity",
"co-translational protein folding and proteostasis",
"protein aggregation prevention"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about NAC being a proteostasis factor that supports longevity is plausible in general terms, but it is factually incorrect for icd-2 in C. elegans. In reality, icd-2/NAC-alpha has been shown to have anti-longevity effects - its loss or reduction actually extends lifespan rather than shortening it. The model confidently asserted that \"loss of NAC function leads to increased protein aggregation and reduced lifespan,\" which is the opposite of what the GenAge database records. The model's mechanistic framework (NAC as proteostasis factor) is reasonable in principle but leads to the wrong conclusion for this specific gene. The model showed moderate confidence (0.65) but was still clearly wrong on both the answer and the mechanism's directional effect.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}