gid-1
C. elegans
B30.2/SPRY domain-containing protein;CTLH domain-containing protein
What the model saw
Gene: gid-1 Organism: Caenorhabditis elegans Known functions: B30.2/SPRY domain-containing protein;CTLH domain-containing protein. protein-macromolecule adaptor activity.
View unredacted entry
B30.2/SPRY domain-containing protein;CTLH domain-containing protein. protein-macromolecule adaptor activity.
Solver output
gid-1 encodes a B30.2/SPRY and CTLH domain-containing protein with protein-macromolecule adaptor activity. The CTLH domain is a hallmark of the GID/CTLH E3 ubiquitin ligase complex, which targets specific substrates for proteasomal degradation and is involved in gluconeogenesis regulation and broader proteostasis. As a substrate-recognition adaptor (via its B30.2/SPRY domain) within this complex, gid-1 would facilitate selective ubiquitin-mediated protein degradation. Proper function of such ubiquitin ligase complexes supports proteostasis by clearing misfolded or unwanted proteins, a process that declines with age. Loss of GID/CTLH complex activity in yeast and metazoans leads to accumulation of aberrant substrates and metabolic dysregulation, consistent with an anti-aging role for the normal gene function. The pro-longevity prediction is tentative, as the specific substrates in C. elegans remain uncertain and could include regulators of growth or nutrient sensing.
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 gid-1, as part of the GID/CTLH E3 ubiquitin ligase complex, would support proteostasis and thus be pro-longevity. However, the ground truth indicates gid-1 is anti_longevity, meaning its loss (or reduction) extends lifespan. The model's mechanistic reasoning is inverted — if gid-1 is anti_longevity, it likely promotes aging or limits lifespan, possibly by degrading pro-longevity substrates or promoting growth/nutrient-sensing pathways that shorten lifespan. The model even acknowledged uncertainty about the specific substrates but still chose the wrong direction. Confidence was low (0.52) but still committed to the wrong answer.
Raw API responses
solver
{
"reasoning": "gid-1 encodes a B30.2/SPRY and CTLH domain-containing protein with protein-macromolecule adaptor activity. The CTLH domain is a hallmark of the GID/CTLH E3 ubiquitin ligase complex, which targets specific substrates for proteasomal degradation and is involved in gluconeogenesis regulation and broader proteostasis. As a substrate-recognition adaptor (via its B30.2/SPRY domain) within this complex, gid-1 would facilitate selective ubiquitin-mediated protein degradation. Proper function of such ubiquitin ligase complexes supports proteostasis by clearing misfolded or unwanted proteins, a process that declines with age. Loss of GID/CTLH complex activity in yeast and metazoans leads to accumulation of aberrant substrates and metabolic dysregulation, consistent with an anti-aging role for the normal gene function. The pro-longevity prediction is tentative, as the specific substrates in C. elegans remain uncertain and could include regulators of growth or nutrient sensing.",
"confidence": 0.52,
"key_pathways": [
"GID/CTLH E3 ubiquitin ligase complex",
"ubiquitin-proteasome proteostasis",
"substrate-recognition adaptor activity"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model reasoned that gid-1, as part of the GID/CTLH E3 ubiquitin ligase complex, would support proteostasis and thus be pro-longevity. However, the ground truth indicates gid-1 is anti_longevity, meaning its loss (or reduction) extends lifespan. The model's mechanistic reasoning is inverted — if gid-1 is anti_longevity, it likely promotes aging or limits lifespan, possibly by degrading pro-longevity substrates or promoting growth/nutrient-sensing pathways that shorten lifespan. The model even acknowledged uncertainty about the specific substrates but still chose the wrong direction. Confidence was low (0.52) but still committed to the wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}