HIR2
S. cerevisiae
Hir2p
What the model saw
Gene: HIR2 Organism: Saccharomyces cerevisiae Known functions: Hir2p. DNA binding. nucleosome binding. protein binding. transcription corepressor activity.
View unredacted entry
Hir2p. DNA binding. nucleosome binding. protein binding. transcription corepressor activity.
Solver output
HIR2 encodes a subunit of the HIR (Histone Regulatory) complex in S. cerevisiae, which functions as a transcription corepressor with nucleosome-binding and DNA-binding activities. The HIR complex is a histone chaperone that promotes chromatin assembly and represses histone gene transcription outside of S-phase, thereby maintaining proper histone stoichiometry and chromatin integrity. Proper nucleosome occupancy and histone homeostasis are critical for preserving epigenetic information and suppressing cryptic transcription, both of which decline with age. By stabilizing chromatin structure and repressing inappropriate transcription, HIR2 helps counteract age-associated epigenetic drift and loss of heterochromatin, which are hallmarks of yeast aging. Loss of HIR complex function leads to dysregulated histone levels and compromised chromatin compaction, phenotypes associated with shortened replicative lifespan in yeast.
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 HIR2 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning about HIR2's role in chromatin assembly and histone homeostasis is generally accurate in terms of molecular function, but the conclusion about its effect on longevity is wrong. The model assumed that because HIR2 maintains chromatin integrity (a generally beneficial function), it must promote longevity. However, the actual data shows HIR2 is anti-longevity, meaning its deletion likely extends lifespan. The model's mechanistic reasoning that "loss of HIR complex function leads to shortened replicative lifespan" is directly contradicted by the ground truth. The model showed moderate confidence (0.65) but still got the direction wrong, and its mechanistic conclusion about what happens upon loss of HIR2 function is incorrect per the GenAge classification.
Raw API responses
solver
{
"reasoning": "HIR2 encodes a subunit of the HIR (Histone Regulatory) complex in S. cerevisiae, which functions as a transcription corepressor with nucleosome-binding and DNA-binding activities. The HIR complex is a histone chaperone that promotes chromatin assembly and represses histone gene transcription outside of S-phase, thereby maintaining proper histone stoichiometry and chromatin integrity. Proper nucleosome occupancy and histone homeostasis are critical for preserving epigenetic information and suppressing cryptic transcription, both of which decline with age. By stabilizing chromatin structure and repressing inappropriate transcription, HIR2 helps counteract age-associated epigenetic drift and loss of heterochromatin, which are hallmarks of yeast aging. Loss of HIR complex function leads to dysregulated histone levels and compromised chromatin compaction, phenotypes associated with shortened replicative lifespan in yeast.",
"confidence": 0.65,
"key_pathways": [
"HIR histone chaperone complex / chromatin assembly",
"histone gene transcription repression",
"nucleosome homeostasis and epigenetic maintenance"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted HIR2 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning about HIR2's role in chromatin assembly and histone homeostasis is generally accurate in terms of molecular function, but the conclusion about its effect on longevity is wrong. The model assumed that because HIR2 maintains chromatin integrity (a generally beneficial function), it must promote longevity. However, the actual data shows HIR2 is anti-longevity, meaning its deletion likely extends lifespan. The model's mechanistic reasoning that \"loss of HIR complex function leads to shortened replicative lifespan\" is directly contradicted by the ground truth. The model showed moderate confidence (0.65) but still got the direction wrong, and its mechanistic conclusion about what happens upon loss of HIR2 function is incorrect per the GenAge classification.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}