Agtr1a
M. musculus
angiotensin II receptor, type 1a
What the model saw
Gene: Agtr1a Organism: Mus musculus Known functions: angiotensin II receptor, type 1a. type-1 angiotensin II receptor A. D1 dopamine receptor binding. G protein-coupled receptor activity. angiotensin type I receptor activity. angiotensin type II receptor activity. bradykinin receptor binding. protein binding. protein heterodimerization activity. protein kinase binding.
View unredacted entry
angiotensin II receptor, type 1a. type-1 angiotensin II receptor A. D1 dopamine receptor binding. G protein-coupled receptor activity. angiotensin type I receptor activity. angiotensin type II receptor activity. bradykinin receptor binding. protein binding. protein heterodimerization activity. protein kinase binding.
Solver output
Agtr1a encodes the type 1a angiotensin II receptor (AT1aR), the primary mediator of angiotensin II signaling in mice. AT1aR activation drives vasoconstriction, oxidative stress (via NADPH oxidase), pro-inflammatory cytokine production, and fibrosis through downstream NF-κB and MAPK pathways. Chronic AT1R signaling accelerates cardiovascular aging, renal fibrosis, and systemic inflammation. Critically, AT1aR knockout mice show extended lifespan and reduced age-related pathology, while pharmacological blockade of AT1R (ARBs) is associated with longevity benefits in multiple model organisms. The receptor's heterodimerization with bradykinin and dopamine receptors further modulates vascular and inflammatory tone, but the dominant effect of AT1aR activity is pro-aging through sustained renin-angiotensin system (RAS) activation.
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 Agtr1a with high confidence (0.82). The mechanistic reasoning is excellent and well-supported: AT1aR (encoded by Agtr1a) is the primary angiotensin II receptor in mice, and its knockout is indeed associated with extended lifespan. The model correctly identifies the key pathways (RAS/NF-κB, NADPH oxidase/ROS, TGF-β/fibrosis) and correctly notes that AT1aR knockout mice show extended lifespan. The reference to ARB (angiotensin receptor blocker) longevity benefits is also accurate. The mechanism class of "chronic_inflammation" is reasonable, though oxidative stress and cardiovascular aging are equally important contributors. Overall, this is a high-quality, accurate prediction with solid mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "Agtr1a encodes the type 1a angiotensin II receptor (AT1aR), the primary mediator of angiotensin II signaling in mice. AT1aR activation drives vasoconstriction, oxidative stress (via NADPH oxidase), pro-inflammatory cytokine production, and fibrosis through downstream NF-κB and MAPK pathways. Chronic AT1R signaling accelerates cardiovascular aging, renal fibrosis, and systemic inflammation. Critically, AT1aR knockout mice show extended lifespan and reduced age-related pathology, while pharmacological blockade of AT1R (ARBs) is associated with longevity benefits in multiple model organisms. The receptor's heterodimerization with bradykinin and dopamine receptors further modulates vascular and inflammatory tone, but the dominant effect of AT1aR activity is pro-aging through sustained renin-angiotensin system (RAS) activation.",
"confidence": 0.82,
"key_pathways": [
"Renin-angiotensin system (RAS) / AT1R-NF-κB pro-inflammatory signaling",
"NADPH oxidase-mediated reactive oxygen species production",
"TGF-β/fibrosis pathway downstream of AT1R"
],
"mechanism_class": "chronic_inflammation",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for Agtr1a with high confidence (0.82). The mechanistic reasoning is excellent and well-supported: AT1aR (encoded by Agtr1a) is the primary angiotensin II receptor in mice, and its knockout is indeed associated with extended lifespan. The model correctly identifies the key pathways (RAS/NF-κB, NADPH oxidase/ROS, TGF-β/fibrosis) and correctly notes that AT1aR knockout mice show extended lifespan. The reference to ARB (angiotensin receptor blocker) longevity benefits is also accurate. The mechanism class of \"chronic_inflammation\" is reasonable, though oxidative stress and cardiovascular aging are equally important contributors. Overall, this is a high-quality, accurate prediction with solid mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}