cdk-12
C. elegans
Cyclin-dependent kinase 12
What the model saw
Gene: cdk-12 Organism: Caenorhabditis elegans Known functions: Cyclin-dependent kinase 12. ATP binding. RNA polymerase II CTD heptapeptide repeat kinase activity. cyclin-dependent protein serine/threonine kinase activity. protein kinase activity. protein serine kinase activity.
View unredacted entry
Cyclin-dependent kinase 12. ATP binding. RNA polymerase II CTD heptapeptide repeat kinase activity. cyclin-dependent protein serine/threonine kinase activity. protein kinase activity. protein serine kinase activity.
Solver output
CDK-12 is a cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) heptapeptide repeats of RNA Polymerase II, a modification critical for transcription elongation, co-transcriptional RNA processing, and the DNA damage response (DDR). In mammals and C. elegans, CDK12 is specifically required for the transcriptional upregulation of DNA repair genes (e.g., homologous recombination factors), and its loss leads to genomic instability through impaired DDR gene expression. By maintaining the transcriptional output of genome-maintenance programs, CDK-12 acts to suppress genomic instability, a primary hallmark of aging. Loss of CDK-12 function in C. elegans is associated with increased sensitivity to genotoxic stress and reduced fitness, consistent with a pro-longevity role for its normal activity. Its role in sustaining RNA Pol II elongation also supports proper proteostasis and stress-response gene expression, further reinforcing 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 correctly predicted pro_longevity for cdk-12 in C. elegans with moderate confidence (0.62). The mechanistic reasoning is well-grounded: CDK-12's role in phosphorylating RNA Pol II CTD, supporting transcription elongation, and maintaining DNA damage response gene expression is consistent with known biology. The model correctly identifies that loss of CDK-12 leads to genomic instability through impaired DDR gene expression, supporting a pro-longevity classification. The reasoning is coherent and biologically plausible, though some specific claims about C. elegans CDK-12 studies may be extrapolated from mammalian data. Overall, this is a solid prediction with appropriate mechanistic justification.
Raw API responses
solver
{
"reasoning": "CDK-12 is a cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) heptapeptide repeats of RNA Polymerase II, a modification critical for transcription elongation, co-transcriptional RNA processing, and the DNA damage response (DDR). In mammals and C. elegans, CDK12 is specifically required for the transcriptional upregulation of DNA repair genes (e.g., homologous recombination factors), and its loss leads to genomic instability through impaired DDR gene expression. By maintaining the transcriptional output of genome-maintenance programs, CDK-12 acts to suppress genomic instability, a primary hallmark of aging. Loss of CDK-12 function in C. elegans is associated with increased sensitivity to genotoxic stress and reduced fitness, consistent with a pro-longevity role for its normal activity. Its role in sustaining RNA Pol II elongation also supports proper proteostasis and stress-response gene expression, further reinforcing longevity.",
"confidence": 0.62,
"key_pathways": [
"RNA Polymerase II CTD phosphorylation and transcription elongation",
"DNA damage response gene transcription (homologous recombination)",
"Cyclin-dependent kinase signaling"
],
"mechanism_class": "genomic_instability",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for cdk-12 in C. elegans with moderate confidence (0.62). The mechanistic reasoning is well-grounded: CDK-12's role in phosphorylating RNA Pol II CTD, supporting transcription elongation, and maintaining DNA damage response gene expression is consistent with known biology. The model correctly identifies that loss of CDK-12 leads to genomic instability through impaired DDR gene expression, supporting a pro-longevity classification. The reasoning is coherent and biologically plausible, though some specific claims about C. elegans CDK-12 studies may be extrapolated from mammalian data. Overall, this is a solid prediction with appropriate mechanistic justification.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}