Fgf23
M. musculus
fibroblast growth factor 23
What the model saw
Gene: Fgf23 Organism: Mus musculus Known functions: fibroblast growth factor 23. fibroblast growth factor receptor binding. growth factor activity. protein binding. type 1 fibroblast growth factor receptor binding.
View unredacted entry
fibroblast growth factor 23. fibroblast growth factor receptor binding. growth factor activity. protein binding. type 1 fibroblast growth factor receptor binding.
Solver output
FGF23 is a phosphaturic hormone that acts as a key regulator of phosphate and vitamin D homeostasis by binding to FGF receptors (particularly FGFR1) in complex with the co-receptor Klotho. Elevated FGF23 signaling suppresses renal 1-alpha-hydroxylase, reducing active vitamin D (1,25-dihydroxyvitamin D3) synthesis, and promotes urinary phosphate excretion. Chronically elevated FGF23 levels are strongly associated with accelerated aging phenotypes, cardiovascular disease, and increased mortality in both mice and humans. Notably, Klotho — the obligate co-receptor for FGF23 — is itself a well-established longevity factor; FGF23 overactivity effectively depletes Klotho signaling capacity and drives the premature aging syndrome seen in Klotho-deficient mice. Thus, FGF23's normal growth factor/receptor-binding activity, when dysregulated upward, promotes mineral metabolism imbalance and accelerated organismal aging, placing it in the deregulated nutrient-sensing hallmark.
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 "anti_longevity" with 0.72 confidence, but the ground truth is "pro_longevity." The model's reasoning is based on the association of elevated FGF23 with aging phenotypes and mortality in humans, and the idea that FGF23 overactivity depletes Klotho signaling. However, the GenAge classification is pro_longevity, which likely reflects that FGF23 knockout/loss-of-function mice show premature aging phenotypes (similar to Klotho-deficient mice), meaning FGF23 is required for normal longevity. The model confused the effects of FGF23 overexpression/elevated levels (which are indeed associated with poor outcomes) with the gene's role in longevity as assessed by loss-of-function studies. The mechanistic reasoning is partially correct in describing FGF23's biology but draws the wrong conclusion about its longevity classification. The model was also fairly confident (0.72) in its wrong answer.
Raw API responses
solver
{
"reasoning": "FGF23 is a phosphaturic hormone that acts as a key regulator of phosphate and vitamin D homeostasis by binding to FGF receptors (particularly FGFR1) in complex with the co-receptor Klotho. Elevated FGF23 signaling suppresses renal 1-alpha-hydroxylase, reducing active vitamin D (1,25-dihydroxyvitamin D3) synthesis, and promotes urinary phosphate excretion. Chronically elevated FGF23 levels are strongly associated with accelerated aging phenotypes, cardiovascular disease, and increased mortality in both mice and humans. Notably, Klotho — the obligate co-receptor for FGF23 — is itself a well-established longevity factor; FGF23 overactivity effectively depletes Klotho signaling capacity and drives the premature aging syndrome seen in Klotho-deficient mice. Thus, FGF23's normal growth factor/receptor-binding activity, when dysregulated upward, promotes mineral metabolism imbalance and accelerated organismal aging, placing it in the deregulated nutrient-sensing hallmark.",
"confidence": 0.72,
"key_pathways": [
"FGF23-Klotho-FGFR1 signaling axis",
"Phosphate/vitamin D homeostasis",
"Renal mineral metabolism"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted \"anti_longevity\" with 0.72 confidence, but the ground truth is \"pro_longevity.\" The model's reasoning is based on the association of elevated FGF23 with aging phenotypes and mortality in humans, and the idea that FGF23 overactivity depletes Klotho signaling. However, the GenAge classification is pro_longevity, which likely reflects that FGF23 knockout/loss-of-function mice show premature aging phenotypes (similar to Klotho-deficient mice), meaning FGF23 is required for normal longevity. The model confused the effects of FGF23 overexpression/elevated levels (which are indeed associated with poor outcomes) with the gene's role in longevity as assessed by loss-of-function studies. The mechanistic reasoning is partially correct in describing FGF23's biology but draws the wrong conclusion about its longevity classification. The model was also fairly confident (0.72) in its wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}