Hex-A
D. melanogaster
Hexokinase A
What the model saw
Gene: Hex-A Organism: Drosophila melanogaster Known functions: Hexokinase A. hexokinase A. ATP binding. D-glucose binding. fructokinase activity. glucokinase activity. glucosamine kinase activity. hexokinase activity. mannokinase activity. protein binding.
View unredacted entry
Hexokinase A. hexokinase A. ATP binding. D-glucose binding. fructokinase activity. glucokinase activity. glucosamine kinase activity. hexokinase activity. mannokinase activity. protein binding.
Solver output
Hexokinase A (Hex-A) catalyzes the first committed step of glycolysis — the phosphorylation of glucose to glucose-6-phosphate — and also phosphorylates fructose, mannose, and glucosamine, making it a central node in carbohydrate metabolism and nutrient sensing. In Drosophila, hexokinase activity is tightly coupled to the insulin/IGF-1 signaling (IIS) and TOR pathways, which are the primary nutrient-sensing axes governing longevity. Proper hexokinase function ensures efficient glucose flux and prevents toxic glucose accumulation, supporting metabolic homeostasis. In multiple model organisms, enhanced glycolytic efficiency and glucose utilization downstream of hexokinase have been linked to improved metabolic health and extended lifespan, while loss of hexokinase activity leads to glucose toxicity and shortened lifespan. Additionally, mitochondrially-associated hexokinase can suppress apoptosis and support mitochondrial integrity, further contributing to pro-longevity effects. Thus, the normal function of Hex-A is predicted to promote longevity by maintaining glucose homeostasis and modulating nutrient-sensing pathway 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 predicted pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning is plausible in general terms (hexokinase as a central metabolic node, glucose homeostasis, IIS/TOR connections) but leads to the wrong conclusion. In Drosophila, Hex-A appears to have an anti-longevity role, meaning its activity shortens lifespan rather than extending it. The model's reasoning about "enhanced glycolytic efficiency" promoting longevity is a reasonable general hypothesis but doesn't match the actual experimental findings for this gene. The model also invokes mitochondrial hexokinase anti-apoptotic effects, which is more relevant to mammalian systems. The mechanistic reasoning is not aligned with the actual biology of Hex-A in Drosophila longevity.
Raw API responses
solver
{
"reasoning": "Hexokinase A (Hex-A) catalyzes the first committed step of glycolysis — the phosphorylation of glucose to glucose-6-phosphate — and also phosphorylates fructose, mannose, and glucosamine, making it a central node in carbohydrate metabolism and nutrient sensing. In Drosophila, hexokinase activity is tightly coupled to the insulin/IGF-1 signaling (IIS) and TOR pathways, which are the primary nutrient-sensing axes governing longevity. Proper hexokinase function ensures efficient glucose flux and prevents toxic glucose accumulation, supporting metabolic homeostasis. In multiple model organisms, enhanced glycolytic efficiency and glucose utilization downstream of hexokinase have been linked to improved metabolic health and extended lifespan, while loss of hexokinase activity leads to glucose toxicity and shortened lifespan. Additionally, mitochondrially-associated hexokinase can suppress apoptosis and support mitochondrial integrity, further contributing to pro-longevity effects. Thus, the normal function of Hex-A is predicted to promote longevity by maintaining glucose homeostasis and modulating nutrient-sensing pathway activity.",
"confidence": 0.72,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) and glucose homeostasis",
"glycolysis / hexose phosphorylation",
"TOR nutrient-sensing pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning is plausible in general terms (hexokinase as a central metabolic node, glucose homeostasis, IIS/TOR connections) but leads to the wrong conclusion. In Drosophila, Hex-A appears to have an anti-longevity role, meaning its activity shortens lifespan rather than extending it. The model's reasoning about \"enhanced glycolytic efficiency\" promoting longevity is a reasonable general hypothesis but doesn't match the actual experimental findings for this gene. The model also invokes mitochondrial hexokinase anti-apoptotic effects, which is more relevant to mammalian systems. The mechanistic reasoning is not aligned with the actual biology of Hex-A in Drosophila longevity.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}