vps-37
C. elegans
VPS37 C-terminal domain-containing protein
What the model saw
Gene: vps-37 Organism: Caenorhabditis elegans Known functions: VPS37 C-terminal domain-containing protein. protein binding.
View unredacted entry
VPS37 C-terminal domain-containing protein. protein binding.
Solver output
VPS37 is a core subunit of the ESCRT-I (Endosomal Sorting Complexes Required for Transport) complex, which is essential for recognizing ubiquitinated cargo and directing it into multivesicular bodies (MVBs) for lysosomal degradation. Proper ESCRT-I function is required for endolysosomal trafficking and autophagic flux; loss of ESCRT components leads to accumulation of damaged proteins and organelles, impairing proteostasis and macroautophagy. In C. elegans, functional endosomal sorting via ESCRT machinery supports clearance of protein aggregates and damaged cellular components, processes that are critical for healthy aging. The VPS37 C-terminal domain mediates protein-protein interactions within the ESCRT-I complex, and disruption of this interaction impairs MVB biogenesis and downstream lysosomal degradation. Thus, normal vps-37 function supports autophagic and endolysosomal degradation pathways that oppose age-related proteotoxicity.
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 vps-37 in C. elegans. The mechanistic reasoning is sound - VPS37 as an ESCRT-I subunit involved in MVB biogenesis and endolysosomal degradation is well-established biology. The connection to proteostasis and healthy aging is reasonable. The confidence of 0.55 is appropriately modest given the limited information provided (only "VPS37 C-terminal domain-containing protein, protein binding" was given). The mechanism class "disabled_macroautophagy" is a reasonable approximation, though the primary pathway is more specifically endosomal sorting/MVB biogenesis rather than classical macroautophagy. Overall a good prediction with solid reasoning.
Raw API responses
solver
{
"reasoning": "VPS37 is a core subunit of the ESCRT-I (Endosomal Sorting Complexes Required for Transport) complex, which is essential for recognizing ubiquitinated cargo and directing it into multivesicular bodies (MVBs) for lysosomal degradation. Proper ESCRT-I function is required for endolysosomal trafficking and autophagic flux; loss of ESCRT components leads to accumulation of damaged proteins and organelles, impairing proteostasis and macroautophagy. In C. elegans, functional endosomal sorting via ESCRT machinery supports clearance of protein aggregates and damaged cellular components, processes that are critical for healthy aging. The VPS37 C-terminal domain mediates protein-protein interactions within the ESCRT-I complex, and disruption of this interaction impairs MVB biogenesis and downstream lysosomal degradation. Thus, normal vps-37 function supports autophagic and endolysosomal degradation pathways that oppose age-related proteotoxicity.",
"confidence": 0.55,
"key_pathways": [
"ESCRT-I complex / multivesicular body (MVB) biogenesis",
"endolysosomal protein degradation",
"macroautophagy / proteostasis"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for vps-37 in C. elegans. The mechanistic reasoning is sound - VPS37 as an ESCRT-I subunit involved in MVB biogenesis and endolysosomal degradation is well-established biology. The connection to proteostasis and healthy aging is reasonable. The confidence of 0.55 is appropriately modest given the limited information provided (only \"VPS37 C-terminal domain-containing protein, protein binding\" was given). The mechanism class \"disabled_macroautophagy\" is a reasonable approximation, though the primary pathway is more specifically endosomal sorting/MVB biogenesis rather than classical macroautophagy. Overall a good prediction with solid reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}