dor
D. melanogaster
deep orange
What the model saw
Gene: dor Organism: Drosophila melanogaster Known functions: deep orange. protein binding. protein-macromolecule adaptor activity. syntaxin binding. ubiquitin protein ligase activity. zinc ion binding.
View unredacted entry
deep orange. protein binding. protein-macromolecule adaptor activity. syntaxin binding. ubiquitin protein ligase activity. zinc ion binding.
Solver output
The Drosophila gene dor (deep orange) encodes a subunit of the HOPS (homotypic fusion and protein sorting) tethering complex, which is essential for late endosome/lysosome fusion and autophagic flux. Its syntaxin-binding activity directly mediates SNARE-dependent membrane fusion events required for autophagosome-lysosome fusion, a critical step in macroautophagy. Loss of dor function impairs lysosomal degradation and autophagy, leading to accumulation of damaged proteins and organelles — a hallmark of aging. The ubiquitin protein ligase and zinc ion binding activities may further contribute to proteostatic regulation via ubiquitin-mediated cargo sorting to the lysosome. Functional dor is therefore required to maintain autophagic flux and proteostasis, processes whose decline accelerates aging, placing dor in a pro-longevity role.
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 pro_longevity for the dor gene. The mechanistic reasoning is well-grounded: dor encodes a HOPS complex subunit involved in late endosome/lysosome fusion and autophagic flux, and its syntaxin-binding activity is relevant to SNARE-mediated membrane fusion. The reasoning about loss of dor impairing lysosomal degradation and autophagy leading to accelerated aging is sound. The model correctly identifies the key pathways. Minor caveat: the "ubiquitin protein ligase activity" attribution to dor is somewhat speculative and may reflect annotation uncertainty, but this doesn't undermine the overall correct prediction and core mechanistic reasoning. Confidence of 0.72 is appropriate given the complexity.
Raw API responses
solver
{
"reasoning": "The Drosophila gene dor (deep orange) encodes a subunit of the HOPS (homotypic fusion and protein sorting) tethering complex, which is essential for late endosome/lysosome fusion and autophagic flux. Its syntaxin-binding activity directly mediates SNARE-dependent membrane fusion events required for autophagosome-lysosome fusion, a critical step in macroautophagy. Loss of dor function impairs lysosomal degradation and autophagy, leading to accumulation of damaged proteins and organelles — a hallmark of aging. The ubiquitin protein ligase and zinc ion binding activities may further contribute to proteostatic regulation via ubiquitin-mediated cargo sorting to the lysosome. Functional dor is therefore required to maintain autophagic flux and proteostasis, processes whose decline accelerates aging, placing dor in a pro-longevity role.",
"confidence": 0.72,
"key_pathways": [
"HOPS complex / autophagosome-lysosome fusion",
"SNARE-mediated membrane trafficking (syntaxin binding)",
"ubiquitin-mediated lysosomal cargo sorting"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for the dor gene. The mechanistic reasoning is well-grounded: dor encodes a HOPS complex subunit involved in late endosome/lysosome fusion and autophagic flux, and its syntaxin-binding activity is relevant to SNARE-mediated membrane fusion. The reasoning about loss of dor impairing lysosomal degradation and autophagy leading to accelerated aging is sound. The model correctly identifies the key pathways. Minor caveat: the \"ubiquitin protein ligase activity\" attribution to dor is somewhat speculative and may reflect annotation uncertainty, but this doesn't undermine the overall correct prediction and core mechanistic reasoning. Confidence of 0.72 is appropriate given the complexity.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}