ddl-1
C. elegans
WASH complex subunit homolog 3
What the model saw
Gene: ddl-1 Organism: Caenorhabditis elegans Known functions: WASH complex subunit homolog 3. protein binding. protein sequestering activity.
View unredacted entry
WASH complex subunit homolog 3. protein binding. protein sequestering activity.
Solver output
DDL-1 is a homolog of WASH complex subunit 3 (WASHC3/FAM21), a component of the WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) complex that regulates endosomal actin polymerization and retromer-mediated endosomal sorting. Its protein sequestering activity suggests it can modulate the availability of specific binding partners, potentially including components of signaling pathways relevant to aging. In C. elegans, proper endosomal trafficking and retromer function are linked to proteostasis and lysosomal degradation pathways; disruption of these processes impairs autophagy flux and lysosomal function, which are critical for longevity. The WASH complex facilitates cargo recycling from endosomes, supporting the integrity of the endomembrane system and preventing accumulation of damaged proteins. Loss of DDL-1 function would be expected to impair endosomal sorting and autophagic clearance, thereby reducing lifespan, making its normal function 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-1 supports endosomal sorting and autophagy flux, so its loss would reduce lifespan — making it pro_longevity. However, the actual finding is that DDL-1 is anti_longevity, meaning its normal function shortens lifespan (or its loss extends lifespan). The model's mechanistic reasoning about WASH complex function in endosomal trafficking is plausible in general terms, but it drew the wrong directional conclusion about DDL-1's effect on longevity. The confidence was moderate (0.55), but the prediction was still wrong in direction. The mechanism class "disabled_macroautophagy" is also questionable as a primary mechanism for a WASH complex subunit.
Raw API responses
solver
{
"reasoning": "DDL-1 is a homolog of WASH complex subunit 3 (WASHC3/FAM21), a component of the WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) complex that regulates endosomal actin polymerization and retromer-mediated endosomal sorting. Its protein sequestering activity suggests it can modulate the availability of specific binding partners, potentially including components of signaling pathways relevant to aging. In C. elegans, proper endosomal trafficking and retromer function are linked to proteostasis and lysosomal degradation pathways; disruption of these processes impairs autophagy flux and lysosomal function, which are critical for longevity. The WASH complex facilitates cargo recycling from endosomes, supporting the integrity of the endomembrane system and preventing accumulation of damaged proteins. Loss of DDL-1 function would be expected to impair endosomal sorting and autophagic clearance, thereby reducing lifespan, making its normal function pro-longevity.",
"confidence": 0.55,
"key_pathways": [
"WASH complex / endosomal actin polymerization",
"retromer-mediated endosomal cargo sorting",
"lysosomal degradation and proteostasis"
],
"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-1 supports endosomal sorting and autophagy flux, so its loss would reduce lifespan — making it pro_longevity. However, the actual finding is that DDL-1 is anti_longevity, meaning its normal function shortens lifespan (or its loss extends lifespan). The model's mechanistic reasoning about WASH complex function in endosomal trafficking is plausible in general terms, but it drew the wrong directional conclusion about DDL-1's effect on longevity. The confidence was moderate (0.55), but the prediction was still wrong in direction. The mechanism class \"disabled_macroautophagy\" is also questionable as a primary mechanism for a WASH complex subunit.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}