rab-7
C. elegans
Ras-related protein Rab-7a
What the model saw
Gene: rab-7 Organism: Caenorhabditis elegans Known functions: Ras-related protein Rab-7a. GTP binding. GTPase activity.
View unredacted entry
Ras-related protein Rab-7a. GTP binding. GTPase activity.
Solver output
RAB-7 is the C. elegans ortholog of Rab7a, a small GTPase that is essential for late endosome maturation and autophagosome-lysosome fusion. Its GTP-binding and GTPase activity cycle drives the tethering and fusion of autophagosomes and late endosomes with lysosomes, a critical step in completing autophagic flux. Functional autophagy is required for the extended lifespan seen in multiple longevity pathways in C. elegans (e.g., daf-2/insulin signaling, dietary restriction, mitophagy). Loss of rab-7 impairs autophagic degradation and lysosomal function, leading to accumulation of damaged organelles and protein aggregates, which accelerates aging. Additionally, RAB-7 supports mitophagy, the selective autophagic clearance of damaged mitochondria, further linking it to mitochondrial quality control and 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 pro_longevity for rab-7 in C. elegans. The mechanistic reasoning is sound: RAB-7 is indeed a key regulator of late endosome maturation and autophagosome-lysosome fusion, and its role in autophagic flux and mitophagy is well-established. The connection to longevity through autophagy pathways in C. elegans is well-supported by the literature. The confidence of 0.72 is reasonable. The mechanism class "disabled_macroautophagy" is a bit oddly named (it seems to describe what happens when rab-7 is lost, rather than the mechanism by which rab-7 promotes longevity), but the reasoning text itself correctly frames RAB-7 as pro-longevity through its role in maintaining autophagic flux. Overall a high-quality prediction with correct answer and largely correct mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "RAB-7 is the C. elegans ortholog of Rab7a, a small GTPase that is essential for late endosome maturation and autophagosome-lysosome fusion. Its GTP-binding and GTPase activity cycle drives the tethering and fusion of autophagosomes and late endosomes with lysosomes, a critical step in completing autophagic flux. Functional autophagy is required for the extended lifespan seen in multiple longevity pathways in C. elegans (e.g., daf-2/insulin signaling, dietary restriction, mitophagy). Loss of rab-7 impairs autophagic degradation and lysosomal function, leading to accumulation of damaged organelles and protein aggregates, which accelerates aging. Additionally, RAB-7 supports mitophagy, the selective autophagic clearance of damaged mitochondria, further linking it to mitochondrial quality control and longevity.",
"confidence": 0.72,
"key_pathways": [
"autophagosome-lysosome fusion",
"late endosome maturation",
"mitophagy"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for rab-7 in C. elegans. The mechanistic reasoning is sound: RAB-7 is indeed a key regulator of late endosome maturation and autophagosome-lysosome fusion, and its role in autophagic flux and mitophagy is well-established. The connection to longevity through autophagy pathways in C. elegans is well-supported by the literature. The confidence of 0.72 is reasonable. The mechanism class \"disabled_macroautophagy\" is a bit oddly named (it seems to describe what happens when rab-7 is lost, rather than the mechanism by which rab-7 promotes longevity), but the reasoning text itself correctly frames RAB-7 as pro-longevity through its role in maintaining autophagic flux. Overall a high-quality prediction with correct answer and largely correct mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}