SWC3
S. cerevisiae
Swc3p
What the model saw
Gene: SWC3 Organism: Saccharomyces cerevisiae Known functions: Swc3p. ATP-dependent H2AZ histone chaperone activity. nucleosomal DNA binding.
View unredacted entry
Swc3p. ATP-dependent H2AZ histone chaperone activity. nucleosomal DNA binding.
Solver output
SWC3 encodes a subunit of the SWR1 chromatin remodeling complex in S. cerevisiae, functioning as an ATP-dependent H2AZ histone chaperone that deposits the histone variant H2A.Z (Htz1) into nucleosomes at specific genomic loci. H2A.Z incorporation is a key epigenetic mark that regulates gene expression, maintains chromatin boundary integrity, and suppresses cryptic transcription — all of which are critical for preserving proper transcriptional programs during aging. Loss of H2A.Z deposition leads to derepression of subtelomeric genes and increased genomic instability, phenotypes associated with accelerated replicative aging in yeast. The SWR1 complex and H2A.Z have been linked to the regulation of stress-response genes and the maintenance of heterochromatin, both of which support longevity. Thus, SWC3's role in facilitating accurate H2A.Z deposition supports epigenetic fidelity and is expected to be 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's reasoning about SWC3's role in the SWR1 complex and H2A.Z deposition is mechanistically plausible in general terms, but it drew the wrong conclusion about the longevity direction. In yeast, H2A.Z (Htz1) incorporation by the SWR1 complex has actually been associated with anti-longevity effects — deletion of SWR1 complex components (including SWC3) tends to extend replicative lifespan, suggesting that H2A.Z deposition is detrimental to longevity rather than beneficial. The model incorrectly assumed that maintaining epigenetic fidelity via H2A.Z deposition would be pro-longevity, when the actual data shows the opposite. The confidence of 0.62 is moderate but still wrong. The mechanistic reasoning about H2A.Z's role in subtelomeric silencing and heterochromatin maintenance was used to support the wrong conclusion.
Raw API responses
solver
{
"reasoning": "SWC3 encodes a subunit of the SWR1 chromatin remodeling complex in S. cerevisiae, functioning as an ATP-dependent H2AZ histone chaperone that deposits the histone variant H2A.Z (Htz1) into nucleosomes at specific genomic loci. H2A.Z incorporation is a key epigenetic mark that regulates gene expression, maintains chromatin boundary integrity, and suppresses cryptic transcription — all of which are critical for preserving proper transcriptional programs during aging. Loss of H2A.Z deposition leads to derepression of subtelomeric genes and increased genomic instability, phenotypes associated with accelerated replicative aging in yeast. The SWR1 complex and H2A.Z have been linked to the regulation of stress-response genes and the maintenance of heterochromatin, both of which support longevity. Thus, SWC3's role in facilitating accurate H2A.Z deposition supports epigenetic fidelity and is expected to be pro-longevity.",
"confidence": 0.62,
"key_pathways": [
"SWR1 chromatin remodeling complex / H2A.Z deposition",
"Nucleosomal epigenetic regulation and heterochromatin maintenance",
"Subtelomeric gene silencing and transcriptional fidelity"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about SWC3's role in the SWR1 complex and H2A.Z deposition is mechanistically plausible in general terms, but it drew the wrong conclusion about the longevity direction. In yeast, H2A.Z (Htz1) incorporation by the SWR1 complex has actually been associated with anti-longevity effects — deletion of SWR1 complex components (including SWC3) tends to extend replicative lifespan, suggesting that H2A.Z deposition is detrimental to longevity rather than beneficial. The model incorrectly assumed that maintaining epigenetic fidelity via H2A.Z deposition would be pro-longevity, when the actual data shows the opposite. The confidence of 0.62 is moderate but still wrong. The mechanistic reasoning about H2A.Z's role in subtelomeric silencing and heterochromatin maintenance was used to support the wrong conclusion.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}