spe-26
C. elegans
Spermatocyte protein spe-26
What the model saw
Gene: spe-26 Organism: Caenorhabditis elegans Known functions: Spermatocyte protein spe-26. ubiquitin-like ligase-substrate adaptor activity.
View unredacted entry
Spermatocyte protein spe-26. ubiquitin-like ligase-substrate adaptor activity.
Solver output
SPE-26 is a spermatocyte-specific protein in C. elegans with ubiquitin-like ligase-substrate adaptor activity, meaning it recruits substrates to ubiquitin E3 ligase complexes for targeted degradation. While ubiquitin-mediated proteolysis is a key component of proteostasis and can influence longevity, SPE-26's function appears restricted to spermatogenesis, limiting its direct role in somatic aging pathways. In C. elegans, germline signals (including sperm vs. oocyte fate) can influence lifespan through DAF-16/FOXO and other pathways, but the specific substrate-adaptor role of SPE-26 in spermatocytes does not clearly map to a pro- or anti-longevity mechanism. The tissue-restricted expression and lack of known somatic targets make it difficult to assign a definitive longevity direction.
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 "unclear" while the ground truth is "anti_longevity." In C. elegans, spe-26 loss-of-function mutations result in sterility (sperm defects), and sterile/germline-deficient worms often live longer due to germline signaling pathways (DAF-16/FOXO, DAF-2/insulin). The model actually touched on germline signaling as a key pathway but failed to connect the dots: loss of spe-26 → sperm defects/sterility → reduced germline proliferation signals → extended lifespan (anti_longevity means the gene normally suppresses longevity, so its loss extends life). The model's reasoning about tissue-restricted expression being a barrier to longevity influence was incorrect given the well-established germline-to-soma signaling in C. elegans lifespan regulation. The model was appropriately uncertain (confidence 0.35) but still got the answer wrong and missed the key mechanistic connection.
Raw API responses
solver
{
"reasoning": "SPE-26 is a spermatocyte-specific protein in C. elegans with ubiquitin-like ligase-substrate adaptor activity, meaning it recruits substrates to ubiquitin E3 ligase complexes for targeted degradation. While ubiquitin-mediated proteolysis is a key component of proteostasis and can influence longevity, SPE-26's function appears restricted to spermatogenesis, limiting its direct role in somatic aging pathways. In C. elegans, germline signals (including sperm vs. oocyte fate) can influence lifespan through DAF-16/FOXO and other pathways, but the specific substrate-adaptor role of SPE-26 in spermatocytes does not clearly map to a pro- or anti-longevity mechanism. The tissue-restricted expression and lack of known somatic targets make it difficult to assign a definitive longevity direction.",
"confidence": 0.35,
"key_pathways": [
"ubiquitin-proteasome system",
"spermatogenesis",
"germline signaling"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" while the ground truth is \"anti_longevity.\" In C. elegans, spe-26 loss-of-function mutations result in sterility (sperm defects), and sterile/germline-deficient worms often live longer due to germline signaling pathways (DAF-16/FOXO, DAF-2/insulin). The model actually touched on germline signaling as a key pathway but failed to connect the dots: loss of spe-26 → sperm defects/sterility → reduced germline proliferation signals → extended lifespan (anti_longevity means the gene normally suppresses longevity, so its loss extends life). The model's reasoning about tissue-restricted expression being a barrier to longevity influence was incorrect given the well-established germline-to-soma signaling in C. elegans lifespan regulation. The model was appropriately uncertain (confidence 0.35) but still got the answer wrong and missed the key mechanistic connection.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}