Socs2
M. musculus
suppressor of cytokine signaling 2
What the model saw
Gene: Socs2 Organism: Mus musculus Known functions: suppressor of cytokine signaling 2. cytokine receptor binding. growth hormone receptor binding. insulin-like growth factor receptor binding. phosphorylation-dependent protein binding. protein binding. ubiquitin-like ligase-substrate adaptor activity.
View unredacted entry
suppressor of cytokine signaling 2. cytokine receptor binding. growth hormone receptor binding. insulin-like growth factor receptor binding. phosphorylation-dependent protein binding. protein binding. ubiquitin-like ligase-substrate adaptor activity.
Solver output
SOCS2 is a classical negative regulator of growth hormone (GH) and IGF-1 receptor signaling, acting as a substrate adaptor for E3 ubiquitin ligase complexes that target activated GH receptor for proteasomal degradation. Suppression of GH/IGF-1 signaling is one of the most robust pro-longevity interventions known across model organisms, including mice (e.g., Ames dwarf, Snell dwarf, GHR-knockout). By attenuating GH receptor and IGF-1 receptor signaling, SOCS2 dampens the PI3K/AKT/mTOR axis, which is a central node of nutrient-sensing deregulation associated with aging. Additionally, SOCS2-mediated suppression of cytokine signaling (e.g., JAK-STAT pathways) reduces chronic low-grade inflammation, another hallmark of aging. Loss of SOCS2 in mice leads to gigantism due to unrestrained GH signaling, phenocopying pro-aging states, while its normal function mimics the longevity-associated reduction in somatotropic axis activity.
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 predicted pro_longevity for Socs2 in Mus musculus. The mechanistic reasoning is excellent and well-grounded: SOCS2 as a negative regulator of GH/IGF-1 signaling via E3 ubiquitin ligase-mediated GHR degradation, the connection to the somatotropic axis and longevity (Ames/Snell dwarf, GHR-KO mice), the downstream PI3K/AKT/mTOR suppression, and the anti-inflammatory effects via JAK-STAT suppression. The observation that Socs2 knockout leads to gigantism (unrestrained GH signaling) phenocopying pro-aging states is accurate and well-reasoned. Confidence of 0.72 is appropriate given the indirect nature of the evidence.
Raw API responses
solver
{
"reasoning": "SOCS2 is a classical negative regulator of growth hormone (GH) and IGF-1 receptor signaling, acting as a substrate adaptor for E3 ubiquitin ligase complexes that target activated GH receptor for proteasomal degradation. Suppression of GH/IGF-1 signaling is one of the most robust pro-longevity interventions known across model organisms, including mice (e.g., Ames dwarf, Snell dwarf, GHR-knockout). By attenuating GH receptor and IGF-1 receptor signaling, SOCS2 dampens the PI3K/AKT/mTOR axis, which is a central node of nutrient-sensing deregulation associated with aging. Additionally, SOCS2-mediated suppression of cytokine signaling (e.g., JAK-STAT pathways) reduces chronic low-grade inflammation, another hallmark of aging. Loss of SOCS2 in mice leads to gigantism due to unrestrained GH signaling, phenocopying pro-aging states, while its normal function mimics the longevity-associated reduction in somatotropic axis activity.",
"confidence": 0.72,
"key_pathways": [
"GH/IGF-1 somatotropic signaling axis",
"JAK-STAT cytokine signaling suppression",
"E3 ubiquitin ligase-mediated GHR degradation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Socs2 in Mus musculus. The mechanistic reasoning is excellent and well-grounded: SOCS2 as a negative regulator of GH/IGF-1 signaling via E3 ubiquitin ligase-mediated GHR degradation, the connection to the somatotropic axis and longevity (Ames/Snell dwarf, GHR-KO mice), the downstream PI3K/AKT/mTOR suppression, and the anti-inflammatory effects via JAK-STAT suppression. The observation that Socs2 knockout leads to gigantism (unrestrained GH signaling) phenocopying pro-aging states is accurate and well-reasoned. Confidence of 0.72 is appropriate given the indirect nature of the evidence.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}