sca-1
C. elegans
Calcium-transporting ATPase
What the model saw
Gene: sca-1 Organism: Caenorhabditis elegans Known functions: Calcium-transporting ATPase. ATP binding. ATP hydrolysis activity. P-type calcium transporter activity. chromatin DNA binding. nucleotide binding.
View unredacted entry
Calcium-transporting ATPase. ATP binding. ATP hydrolysis activity. P-type calcium transporter activity. chromatin DNA binding. nucleotide binding.
Solver output
sca-1 encodes a P-type Ca²⁺-ATPase (SERCA-type pump) in C. elegans responsible for actively transporting calcium into the ER lumen, thereby maintaining cytosolic Ca²⁺ homeostasis. Dysregulation of intracellular calcium is tightly linked to mitochondrial dysfunction: elevated cytosolic Ca²⁺ overloads mitochondria, impairs the electron transport chain, and promotes ROS production and apoptosis. By keeping cytosolic Ca²⁺ low, sca-1 normal function supports mitochondrial integrity and reduces oxidative stress. Additionally, the chromatin DNA binding annotation suggests a possible role in nuclear calcium signaling or transcriptional regulation of stress-response genes, which could further support cellular resilience. Loss of SERCA function in model organisms is associated with ER stress, proteotoxicity, and shortened lifespan, consistent with a pro-longevity role for the wild-type gene.
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 assumed that sca-1 (a SERCA-type Ca²⁺-ATPase) would be pro-longevity because it maintains calcium homeostasis and supports mitochondrial integrity. However, in C. elegans, sca-1 is actually anti-longevity — loss-of-function or reduction of sca-1 extends lifespan rather than shortening it. The model's mechanistic reasoning was plausible in general terms but incorrect for this specific gene in C. elegans. The model even stated "Loss of SERCA function in model organisms is associated with... shortened lifespan" which is the opposite of what is observed for sca-1 in C. elegans. The model had moderate confidence (0.62) but was wrong on both the answer and the mechanism. The mechanism class of "mitochondrial_dysfunction" is also not the primary mechanism — sca-1's anti-longevity role is more related to ER calcium signaling and its interaction with longevity pathways (e.g., reduced sca-1 activity extends lifespan possibly through ER stress hormesis or altered calcium signaling affecting DAF-16/insulin pathway).
Raw API responses
solver
{
"reasoning": "sca-1 encodes a P-type Ca²⁺-ATPase (SERCA-type pump) in C. elegans responsible for actively transporting calcium into the ER lumen, thereby maintaining cytosolic Ca²⁺ homeostasis. Dysregulation of intracellular calcium is tightly linked to mitochondrial dysfunction: elevated cytosolic Ca²⁺ overloads mitochondria, impairs the electron transport chain, and promotes ROS production and apoptosis. By keeping cytosolic Ca²⁺ low, sca-1 normal function supports mitochondrial integrity and reduces oxidative stress. Additionally, the chromatin DNA binding annotation suggests a possible role in nuclear calcium signaling or transcriptional regulation of stress-response genes, which could further support cellular resilience. Loss of SERCA function in model organisms is associated with ER stress, proteotoxicity, and shortened lifespan, consistent with a pro-longevity role for the wild-type gene.",
"confidence": 0.62,
"key_pathways": [
"ER calcium homeostasis / SERCA pump activity",
"mitochondrial calcium buffering and ROS regulation",
"ER stress / unfolded protein response"
],
"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 assumed that sca-1 (a SERCA-type Ca²⁺-ATPase) would be pro-longevity because it maintains calcium homeostasis and supports mitochondrial integrity. However, in C. elegans, sca-1 is actually anti-longevity — loss-of-function or reduction of sca-1 extends lifespan rather than shortening it. The model's mechanistic reasoning was plausible in general terms but incorrect for this specific gene in C. elegans. The model even stated \"Loss of SERCA function in model organisms is associated with... shortened lifespan\" which is the opposite of what is observed for sca-1 in C. elegans. The model had moderate confidence (0.62) but was wrong on both the answer and the mechanism. The mechanism class of \"mitochondrial_dysfunction\" is also not the primary mechanism — sca-1's anti-longevity role is more related to ER calcium signaling and its interaction with longevity pathways (e.g., reduced sca-1 activity extends lifespan possibly through ER stress hormesis or altered calcium signaling affecting DAF-16/insulin pathway).",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}