vps-33.1
C. elegans
Vacuolar protein sorting-associated protein 33A
What the model saw
Gene: vps-33.1 Organism: Caenorhabditis elegans Known functions: Vacuolar protein sorting-associated protein 33A. protein binding.
View unredacted entry
Vacuolar protein sorting-associated protein 33A. protein binding.
Solver output
VPS-33.1 is the C. elegans ortholog of mammalian VPS33A, a Sec1/Munc18 (SM) family protein that is a core subunit of the HOPS (Homotypic fusion and Protein Sorting) tethering complex. This complex is essential for late endosome/lysosome fusion and autophagosome-lysosome fusion, steps critical for productive autophagy and lysosomal degradation. Functional autophagy and lysosomal clearance are well-established pro-longevity mechanisms in C. elegans, as they are required for proteostasis and the lifespan extension seen in daf-2 and dietary restriction paradigms. Loss of HOPS complex function impairs autophagic flux and lysosomal biogenesis, leading to accumulation of damaged proteins and organelles — hallmarks of accelerated aging. Therefore, the normal function of vps-33.1 in supporting autophagosome-lysosome fusion promotes 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 predicted vps-33.1 as pro_longevity. The mechanistic reasoning is sound and well-articulated: VPS-33.1 as a HOPS complex subunit facilitating autophagosome-lysosome fusion, supporting autophagic flux and proteostasis, which are established pro-longevity mechanisms in C. elegans. The confidence of 0.62 is reasonable given the indirect nature of the inference. The mechanism class "disabled_macroautophagy" is slightly imprecise (the gene supports rather than disables macroautophagy), but the reasoning text correctly describes the pro-longevity role. Overall a strong, well-reasoned prediction.
Raw API responses
solver
{
"reasoning": "VPS-33.1 is the C. elegans ortholog of mammalian VPS33A, a Sec1/Munc18 (SM) family protein that is a core subunit of the HOPS (Homotypic fusion and Protein Sorting) tethering complex. This complex is essential for late endosome/lysosome fusion and autophagosome-lysosome fusion, steps critical for productive autophagy and lysosomal degradation. Functional autophagy and lysosomal clearance are well-established pro-longevity mechanisms in C. elegans, as they are required for proteostasis and the lifespan extension seen in daf-2 and dietary restriction paradigms. Loss of HOPS complex function impairs autophagic flux and lysosomal biogenesis, leading to accumulation of damaged proteins and organelles — hallmarks of accelerated aging. Therefore, the normal function of vps-33.1 in supporting autophagosome-lysosome fusion promotes longevity.",
"confidence": 0.62,
"key_pathways": [
"HOPS complex / autophagosome-lysosome fusion",
"lysosomal degradation pathway",
"autophagy-dependent proteostasis"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted vps-33.1 as pro_longevity. The mechanistic reasoning is sound and well-articulated: VPS-33.1 as a HOPS complex subunit facilitating autophagosome-lysosome fusion, supporting autophagic flux and proteostasis, which are established pro-longevity mechanisms in C. elegans. The confidence of 0.62 is reasonable given the indirect nature of the inference. The mechanism class \"disabled_macroautophagy\" is slightly imprecise (the gene supports rather than disables macroautophagy), but the reasoning text correctly describes the pro-longevity role. Overall a strong, well-reasoned prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}