Slc13a1
M. musculus
solute carrier family 13 (sodium/sulfate symporters), member 1
What the model saw
Gene: Slc13a1 Organism: Mus musculus Known functions: solute carrier family 13 (sodium/sulfate symporters), member 1. solute carrier family 13 member 1. monoatomic anion:sodium symporter activity. secondary active sulfate transmembrane transporter activity. sodium:sulfate symporter activity. solute:sodium symporter activity. transmembrane transporter activity.
View unredacted entry
solute carrier family 13 (sodium/sulfate symporters), member 1. solute carrier family 13 member 1. monoatomic anion:sodium symporter activity. secondary active sulfate transmembrane transporter activity. sodium:sulfate symporter activity. solute:sodium symporter activity. transmembrane transporter activity.
Solver output
Slc13a1 encodes the renal sodium/sulfate cotransporter (NaS1), which is the primary mechanism for reabsorbing inorganic sulfate from the glomerular filtrate. Adequate intracellular sulfate availability is essential for sulfation reactions, including the biosynthesis of sulfated proteoglycans, heparan sulfate, chondroitin sulfate, and the sulfation of hormones and xenobiotics via sulfotransferases. Loss of sulfate transport leads to hyposulfatemia, which impairs sulfation of extracellular matrix components and disrupts proteoglycan-dependent signaling pathways critical for tissue homeostasis. Sulfate is also a key substrate for the synthesis of glutathione precursors and taurine, linking sulfate availability to antioxidant defense and mitochondrial function. Maintaining sulfate homeostasis through Slc13a1 activity thus supports multiple anabolic and protective processes that collectively oppose age-related tissue deterioration, placing its normal function in the nutrient/metabolite sensing and homeostasis axis of aging hallmarks.
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 reasoned that Slc13a1 supports sulfate homeostasis and thus promotes tissue health and longevity. However, the GenAge database classifies Slc13a1 as anti_longevity in mice, meaning its normal function actually reduces lifespan (or its loss extends lifespan). This is consistent with research showing that Slc13a1 knockout mice have extended lifespan, likely because reduced sulfate/citrate transport activates beneficial metabolic pathways (similar to how reduced nutrient sensing can extend lifespan). The model's mechanistic reasoning about sulfate homeostasis being beneficial is plausible on its face but leads to the wrong conclusion about longevity influence. The model failed to consider that the transporter's activity might promote aging rather than oppose it. Confidence was 0.55, which is relatively low but still committed to the wrong answer.
Raw API responses
solver
{
"reasoning": "Slc13a1 encodes the renal sodium/sulfate cotransporter (NaS1), which is the primary mechanism for reabsorbing inorganic sulfate from the glomerular filtrate. Adequate intracellular sulfate availability is essential for sulfation reactions, including the biosynthesis of sulfated proteoglycans, heparan sulfate, chondroitin sulfate, and the sulfation of hormones and xenobiotics via sulfotransferases. Loss of sulfate transport leads to hyposulfatemia, which impairs sulfation of extracellular matrix components and disrupts proteoglycan-dependent signaling pathways critical for tissue homeostasis. Sulfate is also a key substrate for the synthesis of glutathione precursors and taurine, linking sulfate availability to antioxidant defense and mitochondrial function. Maintaining sulfate homeostasis through Slc13a1 activity thus supports multiple anabolic and protective processes that collectively oppose age-related tissue deterioration, placing its normal function in the nutrient/metabolite sensing and homeostasis axis of aging hallmarks.",
"confidence": 0.55,
"key_pathways": [
"Sodium-coupled sulfate reabsorption (renal sulfate homeostasis)",
"Sulfated proteoglycan biosynthesis and extracellular matrix maintenance",
"Sulfur amino acid metabolism and antioxidant defense (taurine/glutathione synthesis)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" The model reasoned that Slc13a1 supports sulfate homeostasis and thus promotes tissue health and longevity. However, the GenAge database classifies Slc13a1 as anti_longevity in mice, meaning its normal function actually reduces lifespan (or its loss extends lifespan). This is consistent with research showing that Slc13a1 knockout mice have extended lifespan, likely because reduced sulfate/citrate transport activates beneficial metabolic pathways (similar to how reduced nutrient sensing can extend lifespan). The model's mechanistic reasoning about sulfate homeostasis being beneficial is plausible on its face but leads to the wrong conclusion about longevity influence. The model failed to consider that the transporter's activity might promote aging rather than oppose it. Confidence was 0.55, which is relatively low but still committed to the wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}