Ikbkb
M. musculus
inhibitor of kappaB kinase beta
What the model saw
Gene: Ikbkb Organism: Mus musculus Known functions: inhibitor of kappaB kinase beta. inhibitor of nuclear factor kappa-B kinase subunit beta. ATP binding. IkappaB kinase activity. identical protein binding. protein binding. protein heterodimerization activity. protein homodimerization activity. protein kinase activity. protein kinase binding. protein phosphatase binding. protein serine kinase activity. protein serine/threonine kinase activity. protein-containing complex binding. scaffold protein binding. transferrin receptor binding.
View unredacted entry
inhibitor of kappaB kinase beta. inhibitor of nuclear factor kappa-B kinase subunit beta. ATP binding. IkappaB kinase activity. identical protein binding. protein binding. protein heterodimerization activity. protein homodimerization activity. protein kinase activity. protein kinase binding. protein phosphatase binding. protein serine kinase activity. protein serine/threonine kinase activity. protein-containing complex binding. scaffold protein binding. transferrin receptor binding.
Solver output
IKKβ (encoded by Ikbkb) is the catalytic serine/threonine kinase subunit of the IKK complex that phosphorylates IκB proteins, targeting them for proteasomal degradation and thereby activating NF-κB transcription. NF-κB activation drives expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and is a central mediator of "inflammaging" — the chronic, low-grade sterile inflammation that accumulates with age and accelerates multiple aging hallmarks. Sustained IKKβ activity in aged tissues promotes senescence-associated secretory phenotype (SASP) amplification and systemic inflammation. Genetic or pharmacological inhibition of IKKβ in mice extends healthspan and reduces age-related pathology, consistent with its normal function being detrimental to longevity. Its protein heterodimerization and scaffold-binding activities further anchor it as the key activating kinase within the IKK signalosome driving NF-κB-dependent inflammatory gene programs.
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 anti_longevity for Ikbkb with high confidence (0.85). The mechanistic reasoning is accurate and well-detailed: IKKβ phosphorylates IκB proteins leading to NF-κB activation, which drives chronic inflammation (inflammaging) and SASP amplification. The model correctly identifies that inhibition of IKKβ reduces age-related pathology in mice, making the gene anti-longevity (its normal activity is detrimental to longevity). The key pathways identified are all relevant and correct. The reasoning is thorough and scientifically sound.
Raw API responses
solver
{
"reasoning": "IKKβ (encoded by Ikbkb) is the catalytic serine/threonine kinase subunit of the IKK complex that phosphorylates IκB proteins, targeting them for proteasomal degradation and thereby activating NF-κB transcription. NF-κB activation drives expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and is a central mediator of \"inflammaging\" — the chronic, low-grade sterile inflammation that accumulates with age and accelerates multiple aging hallmarks. Sustained IKKβ activity in aged tissues promotes senescence-associated secretory phenotype (SASP) amplification and systemic inflammation. Genetic or pharmacological inhibition of IKKβ in mice extends healthspan and reduces age-related pathology, consistent with its normal function being detrimental to longevity. Its protein heterodimerization and scaffold-binding activities further anchor it as the key activating kinase within the IKK signalosome driving NF-κB-dependent inflammatory gene programs.",
"confidence": 0.85,
"key_pathways": [
"NF-κB signaling / IKK complex activation",
"Inflammaging / SASP amplification",
"IκB phosphorylation and proteasomal degradation"
],
"mechanism_class": "chronic_inflammation",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for Ikbkb with high confidence (0.85). The mechanistic reasoning is accurate and well-detailed: IKKβ phosphorylates IκB proteins leading to NF-κB activation, which drives chronic inflammation (inflammaging) and SASP amplification. The model correctly identifies that inhibition of IKKβ reduces age-related pathology in mice, making the gene anti-longevity (its normal activity is detrimental to longevity). The key pathways identified are all relevant and correct. The reasoning is thorough and scientifically sound.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}