hook
D. melanogaster
hook
What the model saw
Gene: hook Organism: Drosophila melanogaster Known functions: hook. dynein light intermediate chain binding. microtubule binding. small GTPase binding.
View unredacted entry
hook. dynein light intermediate chain binding. microtubule binding. small GTPase binding.
Solver output
Hook is a dynein adaptor protein that links dynein/dynactin complexes to endosomal and lysosomal cargo via its dynein light intermediate chain binding activity and small GTPase (Rab) interactions. In Drosophila, Hook facilitates minus-end-directed microtubule-based transport of late endosomes and autophagosomes toward lysosomes, a critical step in autophagic flux and endolysosomal degradation. Loss of proper dynein-mediated vesicle trafficking impairs autophagosome-lysosome fusion, leading to accumulation of damaged proteins and organelles — a hallmark of aging. By supporting autophagic clearance and proteostasis through the endolysosomal pathway, Hook's normal function is expected to promote longevity. Its microtubule binding further anchors it to the cytoskeletal machinery required for efficient intracellular trafficking.
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 hook gene in Drosophila melanogaster. The mechanistic reasoning is plausible and well-constructed: Hook as a dynein adaptor facilitating endolysosomal trafficking and autophagic flux is a reasonable explanation for its pro-longevity role. The model appropriately connects dynein light intermediate chain binding and small GTPase (Rab) interactions to vesicle transport and autophagy. The confidence level (0.55) is appropriately moderate given the indirect nature of the inference. The mechanism_class "disabled_macroautophagy" is a reasonable categorization, though it's slightly imprecise since the gene's normal function supports autophagy rather than disabling it — the class label seems to refer to what happens when the gene is lost. Overall, the prediction and reasoning are solid.
Raw API responses
solver
{
"reasoning": "Hook is a dynein adaptor protein that links dynein/dynactin complexes to endosomal and lysosomal cargo via its dynein light intermediate chain binding activity and small GTPase (Rab) interactions. In Drosophila, Hook facilitates minus-end-directed microtubule-based transport of late endosomes and autophagosomes toward lysosomes, a critical step in autophagic flux and endolysosomal degradation. Loss of proper dynein-mediated vesicle trafficking impairs autophagosome-lysosome fusion, leading to accumulation of damaged proteins and organelles — a hallmark of aging. By supporting autophagic clearance and proteostasis through the endolysosomal pathway, Hook's normal function is expected to promote longevity. Its microtubule binding further anchors it to the cytoskeletal machinery required for efficient intracellular trafficking.",
"confidence": 0.55,
"key_pathways": [
"dynein-mediated endolysosomal trafficking",
"autophagosome-lysosome fusion",
"Rab GTPase-dependent vesicle transport"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for the hook gene in Drosophila melanogaster. The mechanistic reasoning is plausible and well-constructed: Hook as a dynein adaptor facilitating endolysosomal trafficking and autophagic flux is a reasonable explanation for its pro-longevity role. The model appropriately connects dynein light intermediate chain binding and small GTPase (Rab) interactions to vesicle transport and autophagy. The confidence level (0.55) is appropriately moderate given the indirect nature of the inference. The mechanism_class \"disabled_macroautophagy\" is a reasonable categorization, though it's slightly imprecise since the gene's normal function supports autophagy rather than disabling it — the class label seems to refer to what happens when the gene is lost. Overall, the prediction and reasoning are solid.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}