egl-9
C. elegans
Hypoxia-inducible factor prolyl hydroxylase
What the model saw
Gene: egl-9 Organism: Caenorhabditis elegans Known functions: Hypoxia-inducible factor prolyl hydroxylase. L-ascorbic acid binding. ferrous iron binding. hypoxia-inducible factor-proline dioxygenase activity. iron ion binding. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen. peptidyl-proline 4-dioxygenase activity. peptidyl-proline dioxygenase activity. protein binding.
View unredacted entry
Hypoxia-inducible factor prolyl hydroxylase. L-ascorbic acid binding. ferrous iron binding. hypoxia-inducible factor-proline dioxygenase activity. iron ion binding. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen. peptidyl-proline 4-dioxygenase activity. peptidyl-proline dioxygenase activity. protein binding.
Solver output
EGL-9 is the C. elegans HIF prolyl hydroxylase that hydroxylates HIF-1α (HIF-1 in worms) on conserved proline residues, targeting it for VHL-mediated ubiquitination and proteasomal degradation. By constitutively suppressing HIF-1 activity under normoxia, EGL-9 acts as a negative regulator of the hypoxia-inducible transcriptional program. Loss-of-function mutations in egl-9 stabilize HIF-1, which has been shown to extend lifespan in C. elegans through downstream metabolic and stress-response gene activation. Thus, the normal function of EGL-9 (degrading HIF-1) opposes the pro-longevity effects of HIF-1 signaling, making it anti-longevity. This places it within deregulated nutrient/oxygen sensing, as HIF-1 integrates oxygen availability with metabolic adaptation analogous to other nutrient-sensing pathways.
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 identifies egl-9 as anti_longevity with high confidence (0.82). The mechanistic reasoning is accurate and detailed: EGL-9 is the HIF prolyl hydroxylase that targets HIF-1 for degradation, and loss-of-function mutations in egl-9 stabilize HIF-1 and extend lifespan in C. elegans. The mechanism class "deregulated_nutrient_sensing" is a reasonable categorization, though "oxygen/hypoxia sensing" might be more precise — the model itself acknowledges this nuance. The key pathways listed are all correct. Overall, this is an excellent prediction with solid mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "EGL-9 is the C. elegans HIF prolyl hydroxylase that hydroxylates HIF-1α (HIF-1 in worms) on conserved proline residues, targeting it for VHL-mediated ubiquitination and proteasomal degradation. By constitutively suppressing HIF-1 activity under normoxia, EGL-9 acts as a negative regulator of the hypoxia-inducible transcriptional program. Loss-of-function mutations in egl-9 stabilize HIF-1, which has been shown to extend lifespan in C. elegans through downstream metabolic and stress-response gene activation. Thus, the normal function of EGL-9 (degrading HIF-1) opposes the pro-longevity effects of HIF-1 signaling, making it anti-longevity. This places it within deregulated nutrient/oxygen sensing, as HIF-1 integrates oxygen availability with metabolic adaptation analogous to other nutrient-sensing pathways.",
"confidence": 0.82,
"key_pathways": [
"HIF-1 prolyl hydroxylation and degradation",
"hypoxia/oxygen sensing pathway",
"VHL-HIF ubiquitin-proteasome axis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identifies egl-9 as anti_longevity with high confidence (0.82). The mechanistic reasoning is accurate and detailed: EGL-9 is the HIF prolyl hydroxylase that targets HIF-1 for degradation, and loss-of-function mutations in egl-9 stabilize HIF-1 and extend lifespan in C. elegans. The mechanism class \"deregulated_nutrient_sensing\" is a reasonable categorization, though \"oxygen/hypoxia sensing\" might be more precise — the model itself acknowledges this nuance. The key pathways listed are all correct. Overall, this is an excellent prediction with solid mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}