Ghr
M. musculus
growth hormone receptor
What the model saw
Gene: Ghr Organism: Mus musculus Known functions: growth hormone receptor. SH2 domain binding. cytokine binding. cytokine receptor activity. growth factor binding. growth hormone receptor activity. identical protein binding. lipid binding. peptide hormone binding. protein binding. protein homodimerization activity. protein kinase binding. protein phosphatase binding. protein tyrosine kinase activator activity. protein tyrosine kinase binding.
View unredacted entry
growth hormone receptor. SH2 domain binding. cytokine binding. cytokine receptor activity. growth factor binding. growth hormone receptor activity. identical protein binding. lipid binding. peptide hormone binding. protein binding. protein homodimerization activity. protein kinase binding. protein phosphatase binding. protein tyrosine kinase activator activity. protein tyrosine kinase binding.
Solver output
The growth hormone receptor (GHR) mediates GH signaling by binding GH and activating JAK2, which phosphorylates downstream effectors including STAT5, and critically activates the IGF-1/PI3K/AKT/mTOR axis — a central nutrient-sensing and growth-promoting pathway. Mice with homozygous deletion of Ghr (Laron dwarf mice) show dramatically extended lifespan (up to ~40%), establishing GHR as a pro-aging gene in mice. GHR's protein tyrosine kinase activator activity and SH2 domain binding directly couple GH binding to JAK-STAT and IRS/PI3K signaling, upregulating IGF-1 production in the liver. Elevated GH/IGF-1 signaling suppresses FOXO transcription factors and activates mTORC1, both of which are well-established drivers of accelerated aging and reduced stress resistance. Thus, normal GHR function promotes growth and anabolism at the cost of longevity.
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 identifies GHR as anti_longevity with high confidence (0.95). The mechanistic reasoning is excellent and accurate: GHR activates JAK2/STAT5 and IGF-1/PI3K/AKT/mTOR signaling, Laron dwarf mice (GHR knockout) show dramatically extended lifespan (~40%), and the model correctly explains how GHR promotes aging through suppression of FOXO and activation of mTORC1. The mechanism class "deregulated_nutrient_sensing" is appropriate given the GH/IGF-1/mTOR axis involvement. All key pathways cited are well-established and correct.
Raw API responses
solver
{
"reasoning": "The growth hormone receptor (GHR) mediates GH signaling by binding GH and activating JAK2, which phosphorylates downstream effectors including STAT5, and critically activates the IGF-1/PI3K/AKT/mTOR axis — a central nutrient-sensing and growth-promoting pathway. Mice with homozygous deletion of Ghr (Laron dwarf mice) show dramatically extended lifespan (up to ~40%), establishing GHR as a pro-aging gene in mice. GHR's protein tyrosine kinase activator activity and SH2 domain binding directly couple GH binding to JAK-STAT and IRS/PI3K signaling, upregulating IGF-1 production in the liver. Elevated GH/IGF-1 signaling suppresses FOXO transcription factors and activates mTORC1, both of which are well-established drivers of accelerated aging and reduced stress resistance. Thus, normal GHR function promotes growth and anabolism at the cost of longevity.",
"confidence": 0.95,
"key_pathways": [
"GH/IGF-1/PI3K/AKT/mTOR signaling",
"JAK2-STAT5 signaling",
"IRS-1/FOXO axis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identifies GHR as anti_longevity with high confidence (0.95). The mechanistic reasoning is excellent and accurate: GHR activates JAK2/STAT5 and IGF-1/PI3K/AKT/mTOR signaling, Laron dwarf mice (GHR knockout) show dramatically extended lifespan (~40%), and the model correctly explains how GHR promotes aging through suppression of FOXO and activation of mTORC1. The mechanism class \"deregulated_nutrient_sensing\" is appropriate given the GH/IGF-1/mTOR axis involvement. All key pathways cited are well-established and correct.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}