Effect of the R406H Substitution on the Normal Function of CHEK2
Bibliographic record
Abstract
CHEK2 (Checkpoint kinase homolog 2) encodes a protein involved in pathways that arrest the cell cycle in response to genomic stress such as DNA damage or replication blocks. Carriers of some of the CHEK2 mutations are at an increased risk of breast cancer. A mutation in the kinase domain of the CHEK2 gene resulting in the R406H substitution has been reported. However, it is currently unknown whether the substitution alters the function of CHEK2 in vitro. We evaluated the effect of the R406H substitution on the normal function of CHEK2 using a yeast complementation assay. The yeast cells lacking Rad53, the yeast homologue of human CHEK2 were transformed with the wild type as well as plasmids carrying mutations resulting in the R406H, 1100delC, and S428F variants. Yeast cells carrying the R406H variant grew at a rate similar to those carrying the wild type CHEK2, whereas the yeast carrying the S428F and 1100delC mutants grew at a slower rate. These results suggest that, unlike the well-known pathogenic alleles such as 1100delC and S428F, the R406H substitution does not abrogate the function of CHEK2. Therefore, this variant is probably not important in development of breast cancer in women.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".