spe-5
C. elegans
V-type proton ATPase subunit B 2
What the model saw
Gene: spe-5 Organism: Caenorhabditis elegans Known functions: V-type proton ATPase subunit B 2. ATP binding. proton-transporting ATPase activity, rotational mechanism.
View unredacted entry
V-type proton ATPase subunit B 2. ATP binding. proton-transporting ATPase activity, rotational mechanism.
Solver output
spe-5 encodes a subunit B of the vacuolar-type H⁺-ATPase (V-ATPase), which uses ATP hydrolysis via a rotational mechanism to acidify intracellular compartments such as lysosomes, endosomes, and autophagosomes. Proper lysosomal acidification is essential for autophagy flux and proteostasis; loss of V-ATPase function impairs lysosomal degradation capacity. In C. elegans, V-ATPase activity is required for normal lysosomal function and has been linked to lifespan regulation through its role in supporting autophagic clearance and mTORC1 nutrient sensing at the lysosomal surface. However, spe-5 is primarily expressed in sperm (spe designation), suggesting its primary physiological role may be in sperm vesicle acidification rather than somatic longevity pathways, which introduces uncertainty about its direct pro-longevity contribution in somatic tissues.
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 focused on general V-ATPase functions in lysosomal acidification, autophagy, and mTORC1 signaling, which are plausible general mechanisms but led to the wrong conclusion. Notably, the model did correctly identify that spe-5 is primarily expressed in sperm (spe designation) and acknowledged uncertainty about its somatic role, but still defaulted to pro_longevity. Since spe-5 is anti_longevity, the likely mechanism is that sperm-related signaling (possibly through germline signaling pathways) promotes aging rather than longevity - a well-known phenomenon in C. elegans where germline signals can shorten lifespan. The model's mechanistic reasoning about V-ATPase supporting autophagy and proteostasis was not aligned with the actual anti-longevity role of this gene. The confidence of 0.55 reflects appropriate uncertainty, but the final call was still wrong.
Raw API responses
solver
{
"reasoning": "spe-5 encodes a subunit B of the vacuolar-type H⁺-ATPase (V-ATPase), which uses ATP hydrolysis via a rotational mechanism to acidify intracellular compartments such as lysosomes, endosomes, and autophagosomes. Proper lysosomal acidification is essential for autophagy flux and proteostasis; loss of V-ATPase function impairs lysosomal degradation capacity. In C. elegans, V-ATPase activity is required for normal lysosomal function and has been linked to lifespan regulation through its role in supporting autophagic clearance and mTORC1 nutrient sensing at the lysosomal surface. However, spe-5 is primarily expressed in sperm (spe designation), suggesting its primary physiological role may be in sperm vesicle acidification rather than somatic longevity pathways, which introduces uncertainty about its direct pro-longevity contribution in somatic tissues.",
"confidence": 0.55,
"key_pathways": [
"V-ATPase lysosomal acidification",
"autophagy flux",
"mTORC1 lysosomal nutrient sensing"
],
"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 focused on general V-ATPase functions in lysosomal acidification, autophagy, and mTORC1 signaling, which are plausible general mechanisms but led to the wrong conclusion. Notably, the model did correctly identify that spe-5 is primarily expressed in sperm (spe designation) and acknowledged uncertainty about its somatic role, but still defaulted to pro_longevity. Since spe-5 is anti_longevity, the likely mechanism is that sperm-related signaling (possibly through germline signaling pathways) promotes aging rather than longevity - a well-known phenomenon in C. elegans where germline signals can shorten lifespan. The model's mechanistic reasoning about V-ATPase supporting autophagy and proteostasis was not aligned with the actual anti-longevity role of this gene. The confidence of 0.55 reflects appropriate uncertainty, but the final call was still wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}