wdr-23
C. elegans
DDB1- and CUL4-associated factor 11 homolog
What the model saw
Gene: wdr-23 Organism: Caenorhabditis elegans Known functions: DDB1- and CUL4-associated factor 11 homolog. RNA polymerase II-specific DNA-binding transcription factor binding. protein binding.
View unredacted entry
DDB1- and CUL4-associated factor 11 homolog. RNA polymerase II-specific DNA-binding transcription factor binding. protein binding.
Solver output
WDR-23 is the C. elegans homolog of DCAF11, a substrate receptor for the CRL4 (CUL4-DDB1) E3 ubiquitin ligase complex. In this role, WDR-23 targets the transcription factor SKN-1 (the C. elegans Nrf2 ortholog) for ubiquitin-mediated proteasomal degradation, thereby suppressing SKN-1/Nrf2-driven transcription of cytoprotective, detoxification, and stress-response genes. Loss of wdr-23 leads to constitutive SKN-1 activation, upregulation of phase II detoxification enzymes and antioxidant programs, and extended lifespan in C. elegans. The RNA Pol II-specific transcription factor binding activity reflects its direct interaction with SKN-1 at target gene promoters. Because WDR-23's normal function is to repress a pro-longevity transcription factor (SKN-1/Nrf2), it acts as an anti-longevity gene.
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 identified wdr-23 as an anti-longevity gene with high confidence (0.82). The mechanistic reasoning is excellent and accurate: WDR-23 functions as a substrate receptor in the CRL4 (CUL4-DDB1) E3 ubiquitin ligase complex that targets SKN-1 (C. elegans Nrf2 ortholog) for proteasomal degradation. Loss of wdr-23 leads to constitutive SKN-1 activation and extended lifespan, making it an anti-longevity gene. The model correctly connected the annotated functions (DDB1- and CUL4-associated factor, RNA Pol II transcription factor binding) to the known biology. The key pathways identified are all relevant and accurate.
Raw API responses
solver
{
"reasoning": "WDR-23 is the C. elegans homolog of DCAF11, a substrate receptor for the CRL4 (CUL4-DDB1) E3 ubiquitin ligase complex. In this role, WDR-23 targets the transcription factor SKN-1 (the C. elegans Nrf2 ortholog) for ubiquitin-mediated proteasomal degradation, thereby suppressing SKN-1/Nrf2-driven transcription of cytoprotective, detoxification, and stress-response genes. Loss of wdr-23 leads to constitutive SKN-1 activation, upregulation of phase II detoxification enzymes and antioxidant programs, and extended lifespan in C. elegans. The RNA Pol II-specific transcription factor binding activity reflects its direct interaction with SKN-1 at target gene promoters. Because WDR-23's normal function is to repress a pro-longevity transcription factor (SKN-1/Nrf2), it acts as an anti-longevity gene.",
"confidence": 0.82,
"key_pathways": [
"SKN-1/Nrf2 oxidative stress response",
"CRL4-DCAF11 ubiquitin E3 ligase complex",
"proteostasis and detoxification gene regulation"
],
"mechanism_class": "other",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identified wdr-23 as an anti-longevity gene with high confidence (0.82). The mechanistic reasoning is excellent and accurate: WDR-23 functions as a substrate receptor in the CRL4 (CUL4-DDB1) E3 ubiquitin ligase complex that targets SKN-1 (C. elegans Nrf2 ortholog) for proteasomal degradation. Loss of wdr-23 leads to constitutive SKN-1 activation and extended lifespan, making it an anti-longevity gene. The model correctly connected the annotated functions (DDB1- and CUL4-associated factor, RNA Pol II transcription factor binding) to the known biology. The key pathways identified are all relevant and accurate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}