ddl-2
C. elegans
WASH complex subunit homolog 1
What the model saw
Gene: ddl-2 Organism: Caenorhabditis elegans Known functions: WASH complex subunit homolog 1. alpha-tubulin binding. protein binding. protein sequestering activity.
View unredacted entry
WASH complex subunit homolog 1. alpha-tubulin binding. protein binding. protein sequestering activity.
Solver output
DDL-2 is a homolog of WASH complex subunit 1 (WASHC1/FAM21), a component of the WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) complex that regulates actin polymerization on endosomes and is critical for endosomal sorting and recycling. Its alpha-tubulin binding and protein sequestering activities suggest roles in cytoskeletal organization and vesicular trafficking. The WASH complex is essential for proper endolysosomal trafficking, which directly supports autophagy flux and proteostasis maintenance—key pro-longevity processes in C. elegans. Loss of WASH complex function impairs endosomal recycling and can disrupt autophagic degradation, suggesting that normal ddl-2 function supports lysosomal integrity and macroautophagy. In C. elegans, proper endolysosomal trafficking is linked to longevity pathways including DAF-16/FOXO and mitophagy, making intact WASH complex activity likely pro-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 predicted pro_longevity but the ground truth is anti_longevity. The model reasoned that DDL-2/WASH complex function supports autophagy and proteostasis, making it pro-longevity. However, the actual finding is that ddl-2 is anti-longevity, meaning its loss (or reduction) extends lifespan, or its presence shortens it. The model's mechanistic reasoning about WASH complex and endolysosomal trafficking is plausible in general terms but leads to the wrong conclusion. The model was also only marginally confident (0.52), showing appropriate uncertainty, but still got both the answer and the mechanism direction wrong. The reasoning quality is low because it failed to consider that ddl-2 might act as an anti-longevity gene (i.e., its inhibition could promote longevity by, for example, reducing protein sequestering that might otherwise inhibit autophagy or longevity pathways).
Raw API responses
solver
{
"reasoning": "DDL-2 is a homolog of WASH complex subunit 1 (WASHC1/FAM21), a component of the WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) complex that regulates actin polymerization on endosomes and is critical for endosomal sorting and recycling. Its alpha-tubulin binding and protein sequestering activities suggest roles in cytoskeletal organization and vesicular trafficking. The WASH complex is essential for proper endolysosomal trafficking, which directly supports autophagy flux and proteostasis maintenance—key pro-longevity processes in C. elegans. Loss of WASH complex function impairs endosomal recycling and can disrupt autophagic degradation, suggesting that normal ddl-2 function supports lysosomal integrity and macroautophagy. In C. elegans, proper endolysosomal trafficking is linked to longevity pathways including DAF-16/FOXO and mitophagy, making intact WASH complex activity likely pro-longevity.",
"confidence": 0.52,
"key_pathways": [
"WASH complex-mediated endosomal recycling",
"endolysosomal trafficking and autophagy flux",
"actin cytoskeleton regulation on endosomes"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model reasoned that DDL-2/WASH complex function supports autophagy and proteostasis, making it pro-longevity. However, the actual finding is that ddl-2 is anti-longevity, meaning its loss (or reduction) extends lifespan, or its presence shortens it. The model's mechanistic reasoning about WASH complex and endolysosomal trafficking is plausible in general terms but leads to the wrong conclusion. The model was also only marginally confident (0.52), showing appropriate uncertainty, but still got both the answer and the mechanism direction wrong. The reasoning quality is low because it failed to consider that ddl-2 might act as an anti-longevity gene (i.e., its inhibition could promote longevity by, for example, reducing protein sequestering that might otherwise inhibit autophagy or longevity pathways).",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}