SLC4A11 Three-Dimensional Homology Model Rationalizes Corneal Dystrophy-Causing Mutations
Bibliographic record
Abstract
O) of basolateral corneal endothelium, whose mutations cause some cases of congenital hereditary endothelial dystrophy and Fuchs endothelial corneal dystrophy. We created a three-dimensional homology model of SLC4A11 membrane domain, using Band 3 (SLC4A1) crystal structure as template. The homology model was assessed in silico and by analysis of mutants designed on the basis of the model. Catalytic pathway mutants p.Glu675Gln, p.His724Arg, and p.His724Ala impaired SLC4A11 transport. p.Ala720Leu, in a region of extended structure of the proposed translocation pore, failed to mature to the cell surface. p.Gly509Lys, located in an open region at the core domain/gate domain interface, had wild-type level of transport function. The molecular phenotype of 37 corneal dystrophy-causing point mutants was rationalized, based on their location in the homology model. Four map to the substrate translocation pathway, 25 to regions of close transmembrane helix packing, three to the dimeric interface, and five lie in extramembraneous loops. The model provides a view of the spectrum of effects of disease mutations on membrane protein structure and provides a tool to analyze pathogenicity of additional newly discovered SLC4A11 mutants.
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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".