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Igf1r

M. musculus

insulin-like growth factor I receptor

What the model saw

Gene: Igf1r
Organism: Mus musculus
Known functions: insulin-like growth factor I receptor. insulin-like growth factor 1 receptor. ATP binding. G-protein alpha-subunit binding. identical protein binding. insulin binding. insulin receptor activity. insulin receptor binding. insulin receptor substrate binding. insulin-like growth factor I binding. insulin-like growth factor binding. insulin-like growth factor receptor activity. phosphatidylinositol 3-kinase binding. protein binding. protein kinase activity. protein transporter activity. protein tyrosine kinase activity. protein-containing complex binding. structural molecule activity. transmembrane receptor protein tyrosine kinase activity.
View unredacted entry
insulin-like growth factor I receptor. insulin-like growth factor 1 receptor. ATP binding. G-protein alpha-subunit binding. identical protein binding. insulin binding. insulin receptor activity. insulin receptor binding. insulin receptor substrate binding. insulin-like growth factor I binding. insulin-like growth factor binding. insulin-like growth factor receptor activity. phosphatidylinositol 3-kinase binding. protein binding. protein kinase activity. protein transporter activity. protein tyrosine kinase activity. protein-containing complex binding. structural molecule activity. transmembrane receptor protein tyrosine kinase activity.

Solver output

Predicted influence
Anti-longevity
Confidence
95%
Mechanism
Deregulated nutrient sensing
Reasoning

IGF1R is the primary receptor for insulin-like growth factor 1 and functions as a transmembrane receptor protein tyrosine kinase that, upon ligand binding, autophosphorylates and recruits insulin receptor substrate (IRS) proteins, leading to activation of the PI3K/AKT/mTOR and RAS/MAPK signaling cascades. This IGF1/insulin signaling axis is a central nutrient-sensing pathway that, when active, suppresses FOXO transcription factors and reduces stress resistance, autophagy, and proteostasis maintenance. Extensive genetic evidence in mice demonstrates that heterozygous or tissue-specific loss-of-function of Igf1r extends lifespan, while overactivation of this pathway accelerates aging phenotypes. The pathway is directly homologous to the C. elegans daf-2/age-1 axis, where reduced signaling is one of the most robust pro-longevity interventions known across model organisms. Thus, the normal (wild-type) function of IGF1R — promoting IGF1 signaling — opposes longevity.

Key pathways
IGF1/insulin signaling (PI3K/AKT/mTOR)FOXO transcription factor suppressionIRS/RAS/MAPK signaling
Longevity influence
Anti-longevity
Lifespan effect
Increase

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

Answer
Correct
Mechanism
Correct
Reasoning quality
5/5
Failure mode
Correct
Notes

The model correctly identified Igf1r as anti_longevity with high confidence (0.95). The mechanistic reasoning is thorough and accurate: IGF1R promotes IGF1/insulin signaling through PI3K/AKT/mTOR and RAS/MAPK pathways, suppresses FOXO transcription factors, and reduces stress resistance. The model correctly notes that loss-of-function of Igf1r extends lifespan in mice, making the wild-type gene anti-longevity. The analogy to C. elegans daf-2 is appropriate and well-established. The mechanism class "deregulated_nutrient_sensing" is appropriate. Overall, an excellent prediction with correct answer and correct mechanistic reasoning.

Raw API responses

solver

{
  "reasoning": "IGF1R is the primary receptor for insulin-like growth factor 1 and functions as a transmembrane receptor protein tyrosine kinase that, upon ligand binding, autophosphorylates and recruits insulin receptor substrate (IRS) proteins, leading to activation of the PI3K/AKT/mTOR and RAS/MAPK signaling cascades. This IGF1/insulin signaling axis is a central nutrient-sensing pathway that, when active, suppresses FOXO transcription factors and reduces stress resistance, autophagy, and proteostasis maintenance. Extensive genetic evidence in mice demonstrates that heterozygous or tissue-specific loss-of-function of Igf1r extends lifespan, while overactivation of this pathway accelerates aging phenotypes. The pathway is directly homologous to the C. elegans daf-2/age-1 axis, where reduced signaling is one of the most robust pro-longevity interventions known across model organisms. Thus, the normal (wild-type) function of IGF1R — promoting IGF1 signaling — opposes longevity.",
  "confidence": 0.95,
  "key_pathways": [
    "IGF1/insulin signaling (PI3K/AKT/mTOR)",
    "FOXO transcription factor suppression",
    "IRS/RAS/MAPK signaling"
  ],
  "mechanism_class": "deregulated_nutrient_sensing",
  "longevity_influence": "anti_longevity"
}

advisor

{
  "notes": "The model correctly identified Igf1r as anti_longevity with high confidence (0.95). The mechanistic reasoning is thorough and accurate: IGF1R promotes IGF1/insulin signaling through PI3K/AKT/mTOR and RAS/MAPK pathways, suppresses FOXO transcription factors, and reduces stress resistance. The model correctly notes that loss-of-function of Igf1r extends lifespan in mice, making the wild-type gene anti-longevity. The analogy to C. elegans daf-2 is appropriate and well-established. The mechanism class \"deregulated_nutrient_sensing\" is appropriate. Overall, an excellent prediction with correct answer and correct mechanistic reasoning.",
  "failure_mode": "correct",
  "answer_correct": true,
  "mechanism_correct": true,
  "reasoning_quality": 5,
  "ground_truth_questionable": false
}