chn-1
C. elegans
E3 ubiquitin-protein ligase CHIP
What the model saw
Gene: chn-1 Organism: Caenorhabditis elegans Known functions: E3 ubiquitin-protein ligase CHIP. Hsp70 protein binding. protein-folding chaperone binding. ubiquitin protein ligase activity. ubiquitin protein ligase binding. ubiquitin-protein transferase activity. ubiquitin-ubiquitin ligase activity.
View unredacted entry
E3 ubiquitin-protein ligase CHIP. Hsp70 protein binding. protein-folding chaperone binding. ubiquitin protein ligase activity. ubiquitin protein ligase binding. ubiquitin-protein transferase activity. ubiquitin-ubiquitin ligase activity.
Solver output
chn-1 encodes the C. elegans ortholog of CHIP (C-terminus of Hsc70-Interacting Protein), an E3 ubiquitin ligase that binds Hsp70/Hsc70 chaperones and targets misfolded or chaperone-bound client proteins for ubiquitin-mediated proteasomal degradation. While CHIP can act as a quality-control E3 ligase, its primary role in the context of proteostasis is to ubiquitinate and degrade chaperone clients, including key longevity-relevant proteins. In C. elegans, loss of chn-1 has been shown to extend lifespan, suggesting that its normal activity limits longevity—likely by promoting degradation of proteins that would otherwise support stress resistance or proteostasis. Specifically, chn-1/CHIP antagonizes the HSP90 and HSP70 chaperone networks by routing their clients to degradation rather than refolding, thereby reducing the overall capacity of the proteostasis network. This places chn-1 as an anti-longevity factor whose normal function undermines the chaperone-mediated protein quality control that is essential for healthy aging.
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 predicts chn-1 as anti_longevity with good confidence (0.72). The mechanistic reasoning is sound: chn-1 encodes the C. elegans CHIP ortholog, an E3 ubiquitin ligase that works with Hsp70/Hsp90 chaperones to target misfolded proteins for proteasomal degradation. The model correctly identifies that loss of chn-1 extends lifespan in C. elegans, making it an anti-longevity gene. The reasoning about CHIP antagonizing chaperone networks by routing clients to degradation rather than refolding is mechanistically plausible. The key pathways identified (HSP70/HSP90 chaperone-assisted PQC, UPS, proteostasis network) are all relevant. Minor note: the framing that CHIP "undermines" proteostasis is somewhat nuanced - CHIP is actually part of the proteostasis network, but its role in degrading certain longevity-relevant proteins (like DAF-16/FOXO targets or stress response proteins) could explain the anti-longevity phenotype. Overall, solid reasoning with correct conclusion.
Raw API responses
solver
{
"reasoning": "chn-1 encodes the C. elegans ortholog of CHIP (C-terminus of Hsc70-Interacting Protein), an E3 ubiquitin ligase that binds Hsp70/Hsc70 chaperones and targets misfolded or chaperone-bound client proteins for ubiquitin-mediated proteasomal degradation. While CHIP can act as a quality-control E3 ligase, its primary role in the context of proteostasis is to ubiquitinate and degrade chaperone clients, including key longevity-relevant proteins. In C. elegans, loss of chn-1 has been shown to extend lifespan, suggesting that its normal activity limits longevity—likely by promoting degradation of proteins that would otherwise support stress resistance or proteostasis. Specifically, chn-1/CHIP antagonizes the HSP90 and HSP70 chaperone networks by routing their clients to degradation rather than refolding, thereby reducing the overall capacity of the proteostasis network. This places chn-1 as an anti-longevity factor whose normal function undermines the chaperone-mediated protein quality control that is essential for healthy aging.",
"confidence": 0.72,
"key_pathways": [
"HSP70/HSP90 chaperone-assisted protein quality control",
"ubiquitin-proteasome system (UPS)",
"proteostasis network"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicts chn-1 as anti_longevity with good confidence (0.72). The mechanistic reasoning is sound: chn-1 encodes the C. elegans CHIP ortholog, an E3 ubiquitin ligase that works with Hsp70/Hsp90 chaperones to target misfolded proteins for proteasomal degradation. The model correctly identifies that loss of chn-1 extends lifespan in C. elegans, making it an anti-longevity gene. The reasoning about CHIP antagonizing chaperone networks by routing clients to degradation rather than refolding is mechanistically plausible. The key pathways identified (HSP70/HSP90 chaperone-assisted PQC, UPS, proteostasis network) are all relevant. Minor note: the framing that CHIP \"undermines\" proteostasis is somewhat nuanced - CHIP is actually part of the proteostasis network, but its role in degrading certain longevity-relevant proteins (like DAF-16/FOXO targets or stress response proteins) could explain the anti-longevity phenotype. Overall, solid reasoning with correct conclusion.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}