arl-8
C. elegans
ADP-ribosylation factor-like protein 8B
What the model saw
Gene: arl-8 Organism: Caenorhabditis elegans Known functions: ADP-ribosylation factor-like protein 8B. GTP binding. GTPase activity.
View unredacted entry
ADP-ribosylation factor-like protein 8B. GTP binding. GTPase activity.
Solver output
ARL-8 (ADP-ribosylation factor-like GTPase 8B) is a small Arf-family GTPase that localizes to lysosomes and regulates lysosomal positioning, motility, and fusion. In C. elegans, arl-8 is required for proper lysosomal function and autophagosome-lysosome fusion, which are critical steps in macroautophagy. Functional autophagy/lysosomal degradation is a well-established pro-longevity pathway in C. elegans, as it clears damaged proteins and organelles. ARL-8 also interacts with the HOPS tethering complex and promotes lysosomal exocytosis, supporting proteostasis. Loss of arl-8 impairs lysosomal trafficking and autophagic flux, phenocopying autophagy-deficient animals that show reduced lifespan, placing its normal function on the pro-longevity side.
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 arl-8 in C. elegans. The mechanistic reasoning is sound and well-grounded: ARL-8 is indeed a lysosomal Arf-family GTPase involved in lysosomal positioning, autophagosome-lysosome fusion, and interaction with the HOPS complex. The logic that loss of arl-8 impairs autophagic flux and reduces lifespan, making its normal function pro-longevity, is consistent with the literature. The confidence of 0.62 is appropriately moderate. The mechanism class "disabled_macroautophagy" is a reasonable categorization, though ARL-8's role is more specifically in lysosomal trafficking/positioning rather than macroautophagy per se. Overall, a well-reasoned and correct prediction.
Raw API responses
solver
{
"reasoning": "ARL-8 (ADP-ribosylation factor-like GTPase 8B) is a small Arf-family GTPase that localizes to lysosomes and regulates lysosomal positioning, motility, and fusion. In C. elegans, arl-8 is required for proper lysosomal function and autophagosome-lysosome fusion, which are critical steps in macroautophagy. Functional autophagy/lysosomal degradation is a well-established pro-longevity pathway in C. elegans, as it clears damaged proteins and organelles. ARL-8 also interacts with the HOPS tethering complex and promotes lysosomal exocytosis, supporting proteostasis. Loss of arl-8 impairs lysosomal trafficking and autophagic flux, phenocopying autophagy-deficient animals that show reduced lifespan, placing its normal function on the pro-longevity side.",
"confidence": 0.62,
"key_pathways": [
"lysosomal positioning and motility",
"autophagosome-lysosome fusion",
"HOPS complex-mediated lysosomal tethering"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for arl-8 in C. elegans. The mechanistic reasoning is sound and well-grounded: ARL-8 is indeed a lysosomal Arf-family GTPase involved in lysosomal positioning, autophagosome-lysosome fusion, and interaction with the HOPS complex. The logic that loss of arl-8 impairs autophagic flux and reduces lifespan, making its normal function pro-longevity, is consistent with the literature. The confidence of 0.62 is appropriately moderate. The mechanism class \"disabled_macroautophagy\" is a reasonable categorization, though ARL-8's role is more specifically in lysosomal trafficking/positioning rather than macroautophagy per se. Overall, a well-reasoned and correct prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}