HXK2
S. cerevisiae
hexokinase 2
What the model saw
Gene: HXK2 Organism: Saccharomyces cerevisiae Known functions: hexokinase 2. ATP binding. D-glucose binding. fructokinase activity. glucokinase activity. hexokinase activity. mannokinase activity. protein binding.
View unredacted entry
hexokinase 2. ATP binding. D-glucose binding. fructokinase activity. glucokinase activity. hexokinase activity. mannokinase activity. protein binding.
Solver output
HXK2 encodes the predominant hexokinase isoform in S. cerevisiae responsible for phosphorylating glucose to glucose-6-phosphate, the first committed step of glycolysis. This positions HXK2 as a central node in glucose sensing and signaling: it is required for glucose repression of respiratory genes via the Snf1/AMPK pathway, effectively suppressing mitochondrial respiration and promoting fermentative growth in the presence of glucose. High glucose flux through HXK2 activates the PKA/Ras nutrient-sensing pathway and suppresses stress-response transcription factors (Msn2/Msn4), which are known pro-longevity effectors. Deletion of HXK2 in yeast has been shown to extend chronological and replicative lifespan by derepressing respiration and mimicking caloric restriction signaling. Thus, the normal function of HXK2 promotes glucose-dependent nutrient sensing that opposes 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 identified HXK2 as anti_longevity with high confidence (0.78). The mechanistic reasoning is excellent and accurate: HXK2 is the predominant hexokinase in yeast, central to glucose repression via Snf1/AMPK, activates PKA/Ras signaling, suppresses Msn2/Msn4 stress-response transcription factors, and its deletion extends lifespan by mimicking caloric restriction. All key pathways identified are relevant and correct. The reasoning is detailed, biologically accurate, and well-connected to the longevity phenotype.
Raw API responses
solver
{
"reasoning": "HXK2 encodes the predominant hexokinase isoform in S. cerevisiae responsible for phosphorylating glucose to glucose-6-phosphate, the first committed step of glycolysis. This positions HXK2 as a central node in glucose sensing and signaling: it is required for glucose repression of respiratory genes via the Snf1/AMPK pathway, effectively suppressing mitochondrial respiration and promoting fermentative growth in the presence of glucose. High glucose flux through HXK2 activates the PKA/Ras nutrient-sensing pathway and suppresses stress-response transcription factors (Msn2/Msn4), which are known pro-longevity effectors. Deletion of HXK2 in yeast has been shown to extend chronological and replicative lifespan by derepressing respiration and mimicking caloric restriction signaling. Thus, the normal function of HXK2 promotes glucose-dependent nutrient sensing that opposes longevity.",
"confidence": 0.78,
"key_pathways": [
"glucose repression / Snf1-AMPK pathway",
"PKA/Ras nutrient-sensing pathway",
"glycolysis and fermentative metabolism"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identified HXK2 as anti_longevity with high confidence (0.78). The mechanistic reasoning is excellent and accurate: HXK2 is the predominant hexokinase in yeast, central to glucose repression via Snf1/AMPK, activates PKA/Ras signaling, suppresses Msn2/Msn4 stress-response transcription factors, and its deletion extends lifespan by mimicking caloric restriction. All key pathways identified are relevant and correct. The reasoning is detailed, biologically accurate, and well-connected to the longevity phenotype.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}