Ncor2
M. musculus
nuclear receptor co-repressor 2
What the model saw
Gene: Ncor2 Organism: Mus musculus Known functions: nuclear receptor co-repressor 2. nuclear receptor corepressor 2. DNA binding. Notch binding. chromatin binding. enzyme activator activity. histone deacetylase binding. nuclear glucocorticoid receptor binding. nuclear receptor binding. nuclear retinoic acid receptor binding. nuclear retinoid X receptor binding. protein binding. protein-containing complex binding. sequence-specific DNA binding. sequence-specific double-stranded DNA binding. transcription corepressor activity.
View unredacted entry
nuclear receptor co-repressor 2. nuclear receptor corepressor 2. DNA binding. Notch binding. chromatin binding. enzyme activator activity. histone deacetylase binding. nuclear glucocorticoid receptor binding. nuclear receptor binding. nuclear retinoic acid receptor binding. nuclear retinoid X receptor binding. protein binding. protein-containing complex binding. sequence-specific DNA binding. sequence-specific double-stranded DNA binding. transcription corepressor activity.
Solver output
NCOR2 (also known as SMRT) is a transcriptional corepressor that recruits histone deacetylase (HDAC) complexes to nuclear receptors, including glucocorticoid receptors, retinoic acid receptors, and retinoid X receptors, thereby repressing their target gene transcription. By modulating HDAC activity and chromatin compaction, NCOR2 helps maintain proper epigenetic regulation of metabolic and inflammatory gene programs. NCOR2 is a critical corepressor for nuclear receptors involved in metabolic homeostasis (e.g., PPARγ, LXR, TR), and its activity suppresses pro-inflammatory and lipogenic transcriptional programs that are associated with accelerated aging. Additionally, NCOR2 interacts with the Notch signaling pathway, which plays roles in stem cell maintenance and tissue homeostasis. Loss of NCOR2 function leads to derepression of metabolic and inflammatory gene networks, contributing to metabolic dysfunction and chronic inflammation — hallmarks of aging — suggesting its normal function is pro-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 predicted pro_longevity for Ncor2. The mechanistic reasoning is sound and well-grounded: NCOR2/SMRT is indeed a nuclear receptor corepressor that recruits HDAC complexes, modulates epigenetic regulation, and suppresses pro-inflammatory and metabolic gene programs associated with aging. The model appropriately connects NCOR2's corepressor activity to metabolic homeostasis and inflammation control, both hallmarks of aging. The reasoning about Notch signaling and stem cell homeostasis is also plausible given the known functions listed. The confidence level of 0.65 is reasonable given that this is not the most commonly studied longevity gene. Overall, the prediction and mechanistic explanation are well-reasoned and correct.
Raw API responses
solver
{
"reasoning": "NCOR2 (also known as SMRT) is a transcriptional corepressor that recruits histone deacetylase (HDAC) complexes to nuclear receptors, including glucocorticoid receptors, retinoic acid receptors, and retinoid X receptors, thereby repressing their target gene transcription. By modulating HDAC activity and chromatin compaction, NCOR2 helps maintain proper epigenetic regulation of metabolic and inflammatory gene programs. NCOR2 is a critical corepressor for nuclear receptors involved in metabolic homeostasis (e.g., PPARγ, LXR, TR), and its activity suppresses pro-inflammatory and lipogenic transcriptional programs that are associated with accelerated aging. Additionally, NCOR2 interacts with the Notch signaling pathway, which plays roles in stem cell maintenance and tissue homeostasis. Loss of NCOR2 function leads to derepression of metabolic and inflammatory gene networks, contributing to metabolic dysfunction and chronic inflammation — hallmarks of aging — suggesting its normal function is pro-longevity.",
"confidence": 0.65,
"key_pathways": [
"nuclear receptor corepressor/HDAC complex-mediated chromatin silencing",
"glucocorticoid/retinoic acid receptor transcriptional repression",
"Notch signaling and stem cell homeostasis"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Ncor2. The mechanistic reasoning is sound and well-grounded: NCOR2/SMRT is indeed a nuclear receptor corepressor that recruits HDAC complexes, modulates epigenetic regulation, and suppresses pro-inflammatory and metabolic gene programs associated with aging. The model appropriately connects NCOR2's corepressor activity to metabolic homeostasis and inflammation control, both hallmarks of aging. The reasoning about Notch signaling and stem cell homeostasis is also plausible given the known functions listed. The confidence level of 0.65 is reasonable given that this is not the most commonly studied longevity gene. Overall, the prediction and mechanistic explanation are well-reasoned and correct.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}