Characterization of human mutations in phosphorylatable amino acids of the cytosolic regulatory tail of SLC9A1
Bibliographic record
Abstract
The NHE1 isoform of the mammalian Na(+)/H(+) exchanger is a ubiquitous plasma membrane protein that regulates intracellular pH in cells by removing one intracellular proton in exchange for one extracellular sodium. Genetic defects in NHE1 have been shown to affect the growth and motor ability of mice, but mutations in humans have not been studied. NHE1 has a cytosolic C-terminal regulatory domain of approximately 300 amino acids. We investigated the functional effects of two human mutations found in the regulatory phosphorylatable amino acids Ser(703) and Ser(771). A Ser703Pro mutant protein had essentially the same activity, expression, and targeting as the wild type NHE1 protein. In contrast, the Ser771Pro protein had reduced activity and expression of NHE1 protein, though cell surface targeting was normal. In dual pulse assays the Ser771Pro mutant was not further activated by sustained intracellular acidosis but displayed an unusual activation by brief pulses of acidosis. The results demonstrate that the Ser771Pro human genetic mutation has significant and detrimental physiological effects on the activity of the NHE1 protein, SLC9A1.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".