Kl
M. musculus
klotho
What the model saw
Gene: Kl Organism: Mus musculus Known functions: klotho. beta-glucuronidase activity. fibroblast growth factor binding. fibroblast growth factor receptor binding. hydrolase activity, hydrolyzing O-glycosyl compounds. protein binding.
View unredacted entry
klotho. beta-glucuronidase activity. fibroblast growth factor binding. fibroblast growth factor receptor binding. hydrolase activity, hydrolyzing O-glycosyl compounds. protein binding.
Solver output
Klotho (Kl) is a well-established aging suppressor in mice; Kl knockout mice display a dramatic premature aging syndrome, while Kl overexpression extends lifespan. At the molecular level, Klotho functions as an obligate co-receptor for FGF23 by binding fibroblast growth factor receptor (FGFR) and FGF23, thereby modulating phosphate/vitamin D homeostasis and suppressing insulin/IGF-1 signaling — a canonical nutrient-sensing pathway linked to longevity. Its beta-glucuronidase and O-glycosyl hydrolase activities are involved in cleaving sugar moieties from membrane proteins (e.g., activating TRPV5 channels and modulating Wnt ligand glycosylation), contributing to ion homeostasis and suppression of Wnt/IGF-1 pro-aging signals. Loss of Klotho leads to hyperphosphatemia, accelerated vascular calcification, and systemic aging phenotypes, placing it squarely in the deregulated nutrient-sensing hallmark. The FGF23-Klotho-FGFR axis also intersects with mTOR and insulin/IGF-1 signaling, further reinforcing its pro-longevity role.
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 correctly identified Kl (Klotho) as pro_longevity with very high confidence (0.97). The mechanistic reasoning is excellent and accurate: Kl knockout mice show premature aging, overexpression extends lifespan, and the molecular mechanisms described (FGF23-FGFR co-receptor function, phosphate/vitamin D homeostasis, insulin/IGF-1 signaling suppression, beta-glucuronidase/O-glycosyl hydrolase activities) are all well-established and correct. The classification as "deregulated_nutrient_sensing" is reasonable given the insulin/IGF-1 and FGF23 signaling connections. The reasoning is detailed, accurate, and well-supported by the literature.
Raw API responses
solver
{
"reasoning": "Klotho (Kl) is a well-established aging suppressor in mice; Kl knockout mice display a dramatic premature aging syndrome, while Kl overexpression extends lifespan. At the molecular level, Klotho functions as an obligate co-receptor for FGF23 by binding fibroblast growth factor receptor (FGFR) and FGF23, thereby modulating phosphate/vitamin D homeostasis and suppressing insulin/IGF-1 signaling — a canonical nutrient-sensing pathway linked to longevity. Its beta-glucuronidase and O-glycosyl hydrolase activities are involved in cleaving sugar moieties from membrane proteins (e.g., activating TRPV5 channels and modulating Wnt ligand glycosylation), contributing to ion homeostasis and suppression of Wnt/IGF-1 pro-aging signals. Loss of Klotho leads to hyperphosphatemia, accelerated vascular calcification, and systemic aging phenotypes, placing it squarely in the deregulated nutrient-sensing hallmark. The FGF23-Klotho-FGFR axis also intersects with mTOR and insulin/IGF-1 signaling, further reinforcing its pro-longevity role.",
"confidence": 0.97,
"key_pathways": [
"FGF23-FGFR-Klotho signaling (phosphate/vitamin D homeostasis)",
"Insulin/IGF-1 signaling suppression",
"Wnt signaling modulation via O-glycosyl hydrolase activity"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified Kl (Klotho) as pro_longevity with very high confidence (0.97). The mechanistic reasoning is excellent and accurate: Kl knockout mice show premature aging, overexpression extends lifespan, and the molecular mechanisms described (FGF23-FGFR co-receptor function, phosphate/vitamin D homeostasis, insulin/IGF-1 signaling suppression, beta-glucuronidase/O-glycosyl hydrolase activities) are all well-established and correct. The classification as \"deregulated_nutrient_sensing\" is reasonable given the insulin/IGF-1 and FGF23 signaling connections. The reasoning is detailed, accurate, and well-supported by the literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}