The C-type lectin receptor CLEC4M binds, internalizes, and clears von Willebrand factor and contributes to the variation in plasma von Willebrand factor levels
Bibliographic record
Abstract
Genetic variation in or near the C-type lectin domain family 4 member M (CLEC4M) has been associated with plasma levels of von Willebrand factor (VWF) in healthy individuals. CLEC4M is a lectin receptor with a polymorphic extracellular neck region possessing a variable number of tandem repeats (VNTR). A total of 491 participants (318 patients with type 1 von Willebrand disease [VWD] and 173 unaffected family members) were genotyped for the CLEC4M VNTR polymorphism. Family-based association analysis on kindreds with type 1 VWD demonstrated an excess transmission of VNTR 6 to unaffected individuals (P = .0096) and an association of this allele with increased VWF:RCo (P = .029). CLEC4M-Fc bound to VWF. Immunofluorescence and enzyme-linked immunosorbent assay demonstrated that HEK 293 cells transfected with CLEC4M bound and internalized VWF. Cells expressing 4 or 9 copies of the CLEC4M neck region VNTR showed reduced interaction with VWF relative to CLEC4M with 7 VNTR (CLEC4M 4%-60% reduction, P < .001; CLEC4M 9%-45% reduction, P = .006). Mice expressing CLEC4M after hydrodynamic liver transfer have a 46% decrease in plasma levels of VWF (P = .0094). CLEC4M binds to and internalizes VWF, and polymorphisms in the CLEC4M gene contribute to variable plasma levels of VWF.
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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 | 0.000 |
| 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".