hmg-4
C. elegans
FACT complex subunit SSRP1-A
What the model saw
Gene: hmg-4 Organism: Caenorhabditis elegans Known functions: FACT complex subunit SSRP1-A. DNA binding. histone binding. nucleosome binding.
View unredacted entry
FACT complex subunit SSRP1-A. DNA binding. histone binding. nucleosome binding.
Solver output
hmg-4 encodes the SSRP1-A subunit of the FACT (Facilitates Chromatin Transcription) complex, which functions as a histone chaperone that reorganizes nucleosomes to enable transcription and DNA repair. The FACT complex maintains chromatin integrity and proper epigenetic states by binding histones and nucleosomes, facilitating controlled access to chromatin. In C. elegans, FACT complex components have been shown to support transcriptional fidelity and chromatin organization, which are critical for maintaining gene expression patterns that decline with age. Loss of FACT function leads to aberrant transcription and chromatin disorganization, hallmarks of epigenetic drift associated with aging. By preserving nucleosome positioning and histone modification landscapes, hmg-4/SSRP1-A is expected to oppose age-related epigenetic deterioration and thereby promote 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 assumed that FACT complex activity (via hmg-4/SSRP1-A) promotes longevity by maintaining chromatin integrity and transcriptional fidelity. However, in C. elegans, FACT complex components like hmg-4 have been shown to be anti-longevity — their loss or reduction actually extends lifespan, likely because FACT activity supports transcriptional programs that promote growth and reproduction at the expense of longevity. The model's mechanistic reasoning was plausible on the surface but missed the key finding that FACT complex activity in C. elegans is associated with reduced lifespan (anti_longevity). The model had moderate confidence (0.62) but was still clearly wrong in both the direction of effect and the mechanistic interpretation.
Raw API responses
solver
{
"reasoning": "hmg-4 encodes the SSRP1-A subunit of the FACT (Facilitates Chromatin Transcription) complex, which functions as a histone chaperone that reorganizes nucleosomes to enable transcription and DNA repair. The FACT complex maintains chromatin integrity and proper epigenetic states by binding histones and nucleosomes, facilitating controlled access to chromatin. In C. elegans, FACT complex components have been shown to support transcriptional fidelity and chromatin organization, which are critical for maintaining gene expression patterns that decline with age. Loss of FACT function leads to aberrant transcription and chromatin disorganization, hallmarks of epigenetic drift associated with aging. By preserving nucleosome positioning and histone modification landscapes, hmg-4/SSRP1-A is expected to oppose age-related epigenetic deterioration and thereby promote longevity.",
"confidence": 0.62,
"key_pathways": [
"FACT complex-mediated chromatin remodeling",
"histone chaperone activity and nucleosome maintenance",
"epigenetic regulation of 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 assumed that FACT complex activity (via hmg-4/SSRP1-A) promotes longevity by maintaining chromatin integrity and transcriptional fidelity. However, in C. elegans, FACT complex components like hmg-4 have been shown to be anti-longevity — their loss or reduction actually extends lifespan, likely because FACT activity supports transcriptional programs that promote growth and reproduction at the expense of longevity. The model's mechanistic reasoning was plausible on the surface but missed the key finding that FACT complex activity in C. elegans is associated with reduced lifespan (anti_longevity). The model had moderate confidence (0.62) but was still clearly wrong in both the direction of effect and the mechanistic interpretation.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}