lin-40
C. elegans
DIOX_N domain-containing protein;ELM2 domain-containing protein
What the model saw
Gene: lin-40 Organism: Caenorhabditis elegans Known functions: DIOX_N domain-containing protein;ELM2 domain-containing protein. chromatin binding. histone deacetylase binding. protein binding. sequence-specific DNA binding. transcription coactivator activity. transcription corepressor activity.
View unredacted entry
DIOX_N domain-containing protein;ELM2 domain-containing protein. chromatin binding. histone deacetylase binding. protein binding. sequence-specific DNA binding. transcription coactivator activity. transcription corepressor activity.
Solver output
lin-40 encodes a MTA (Metastasis-Associated protein) family chromatin remodeling factor in C. elegans, characterized by ELM2 and DIOX_N domains, which are hallmarks of the NuRD (Nucleosome Remodeling and Deacetylase) complex scaffold subunit. Its binding to histone deacetylases (HDACs) and chromatin positions it as a core component of transcriptional repression machinery. HDAC-containing NuRD complexes silence genes involved in stress resistance, DAF-16/FOXO target gene expression, and longevity-promoting transcriptional programs. By acting as a transcription corepressor and recruiting HDACs to chromatin, lin-40 likely suppresses pro-longevity gene expression networks, including those downstream of the insulin/IGF-1 signaling pathway. Loss-of-function of NuRD complex components in C. elegans has been associated with extended lifespan, consistent with an anti-longevity role for lin-40.
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 anti_longevity but the ground truth is pro_longevity. The model's reasoning about lin-40 as a NuRD complex component suppressing pro-longevity gene expression is plausible in general terms but leads to the wrong conclusion. The model assumed that HDAC-containing complexes and transcriptional repression would suppress longevity pathways, but lin-40 in C. elegans actually promotes longevity. The mechanistic reasoning is also incorrect - lin-40 appears to have a pro-longevity role, which contradicts the model's claim that NuRD complex components' loss-of-function extends lifespan. The model had moderate confidence (0.62) in the wrong direction.
Raw API responses
solver
{
"reasoning": "lin-40 encodes a MTA (Metastasis-Associated protein) family chromatin remodeling factor in C. elegans, characterized by ELM2 and DIOX_N domains, which are hallmarks of the NuRD (Nucleosome Remodeling and Deacetylase) complex scaffold subunit. Its binding to histone deacetylases (HDACs) and chromatin positions it as a core component of transcriptional repression machinery. HDAC-containing NuRD complexes silence genes involved in stress resistance, DAF-16/FOXO target gene expression, and longevity-promoting transcriptional programs. By acting as a transcription corepressor and recruiting HDACs to chromatin, lin-40 likely suppresses pro-longevity gene expression networks, including those downstream of the insulin/IGF-1 signaling pathway. Loss-of-function of NuRD complex components in C. elegans has been associated with extended lifespan, consistent with an anti-longevity role for lin-40.",
"confidence": 0.62,
"key_pathways": [
"NuRD (Nucleosome Remodeling and Deacetylase) complex / HDAC-mediated transcriptional repression",
"DAF-16/FOXO target gene silencing via chromatin compaction",
"Insulin/IGF-1 signaling longevity pathway"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity but the ground truth is pro_longevity. The model's reasoning about lin-40 as a NuRD complex component suppressing pro-longevity gene expression is plausible in general terms but leads to the wrong conclusion. The model assumed that HDAC-containing complexes and transcriptional repression would suppress longevity pathways, but lin-40 in C. elegans actually promotes longevity. The mechanistic reasoning is also incorrect - lin-40 appears to have a pro-longevity role, which contradicts the model's claim that NuRD complex components' loss-of-function extends lifespan. The model had moderate confidence (0.62) in the wrong direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}