y39b6a.3
C. elegans
Iron-sulfur cluster assembly 1 homolog, mitochondrial
What the model saw
Gene: Y39B6A.3 Organism: Caenorhabditis elegans Known functions: Iron-sulfur cluster assembly 1 homolog, mitochondrial. 2 iron, 2 sulfur cluster binding. iron-sulfur cluster binding.
View unredacted entry
Iron-sulfur cluster assembly 1 homolog, mitochondrial. 2 iron, 2 sulfur cluster binding. iron-sulfur cluster binding.
Solver output
Y39B6A.3 encodes the C. elegans homolog of Iron-Sulfur Cluster Assembly 1 (ISCA1), a mitochondrial protein essential for the assembly and delivery of [2Fe-2S] clusters to recipient apoproteins. Iron-sulfur (Fe-S) clusters are critical cofactors for the mitochondrial electron transport chain complexes (I, II, and III), and their proper assembly is required for efficient oxidative phosphorylation and mitochondrial respiratory function. Loss of Fe-S cluster assembly leads to mitochondrial dysfunction, impaired ATP production, and elevated reactive oxygen species — all hallmarks of accelerated aging. Conversely, normal ISCA1 function maintains mitochondrial integrity and bioenergetic capacity, which is broadly associated with healthy aging and longevity in C. elegans. This places the gene squarely within the mitochondrial dysfunction hallmark of aging, where its normal activity is protective.
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 assumes that because ISCA1 maintains mitochondrial integrity, its normal function should be protective/pro-longevity. However, in C. elegans, mitochondrial electron transport chain (ETC) components often show anti-longevity effects — reduced ETC function (e.g., via RNAi knockdown of complex I or II subunits) frequently extends lifespan through mechanisms like reduced ROS production or activation of mitohormesis pathways. The model failed to consider that in C. elegans, normal/high mitochondrial respiratory function is often associated with shorter lifespan, not longer. The gene is classified as anti_longevity, meaning its normal activity shortens lifespan (or its loss extends lifespan). The model's mechanistic reasoning, while internally consistent, applies a mammalian-centric view that doesn't account for the well-established C. elegans paradigm where mitochondrial dysfunction can paradoxically extend lifespan. The confidence of 0.72 is notably high for an incorrect prediction.
Raw API responses
solver
{
"reasoning": "Y39B6A.3 encodes the C. elegans homolog of Iron-Sulfur Cluster Assembly 1 (ISCA1), a mitochondrial protein essential for the assembly and delivery of [2Fe-2S] clusters to recipient apoproteins. Iron-sulfur (Fe-S) clusters are critical cofactors for the mitochondrial electron transport chain complexes (I, II, and III), and their proper assembly is required for efficient oxidative phosphorylation and mitochondrial respiratory function. Loss of Fe-S cluster assembly leads to mitochondrial dysfunction, impaired ATP production, and elevated reactive oxygen species — all hallmarks of accelerated aging. Conversely, normal ISCA1 function maintains mitochondrial integrity and bioenergetic capacity, which is broadly associated with healthy aging and longevity in C. elegans. This places the gene squarely within the mitochondrial dysfunction hallmark of aging, where its normal activity is protective.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial iron-sulfur cluster assembly",
"electron transport chain complex biogenesis",
"mitochondrial oxidative phosphorylation"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumes that because ISCA1 maintains mitochondrial integrity, its normal function should be protective/pro-longevity. However, in C. elegans, mitochondrial electron transport chain (ETC) components often show anti-longevity effects — reduced ETC function (e.g., via RNAi knockdown of complex I or II subunits) frequently extends lifespan through mechanisms like reduced ROS production or activation of mitohormesis pathways. The model failed to consider that in C. elegans, normal/high mitochondrial respiratory function is often associated with shorter lifespan, not longer. The gene is classified as anti_longevity, meaning its normal activity shortens lifespan (or its loss extends lifespan). The model's mechanistic reasoning, while internally consistent, applies a mammalian-centric view that doesn't account for the well-established C. elegans paradigm where mitochondrial dysfunction can paradoxically extend lifespan. The confidence of 0.72 is notably high for an incorrect prediction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}