Functional Significance of the C324R Mutation Examined Using a Structural Biological Approach
Bibliographic record
Abstract
To the Editor: We read with interest in The Journal of Rheumatology the letter from Maeshima, et al , “An Adult Fatal Case with a STAT1 Gain-of-function Mutation Associated with Multiple Autoimmune Diseases”1. The authors presented the case of a 25-year-old Japanese woman, who was diagnosed at 8 years of age with autoimmune hypothyroidism, and accidentally at 21 years with Takayasu arteritis (TA). By using DNA sequencing, they identified a signal transducer and activator of transcription 1 ( STAT1 ) gain-of-function (GOF) c.970T>C (p.C324R) mutation, in the DNA binding domain of STAT1 protein. STAT1 is one of the 7-member mammalian STAT family and latent DNA-binding protein mediating transmission from various signals to specific gene expression2. Although hypothyroidism, inflammatory bowel disease, and thrombocytopenia are common autoimmune features of STAT1 GOF mutations3, TA represents a previously unreported phenotype of STAT1 GOF mutations1. Prompted by this unique finding, and considering that … Address correspondence to G. Goulielmos, Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, Heraklion, Greece. E-mail: goulielmos{at}med.uoc.gr
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".