OneLetterLottery
It is tempting to think that changing one letter in a protein’s recipe always breaks it. Usually it doesn’t: most single amino-acid changes change little or nothing, a few change everything — and the same spot can go either way. Draw a real variant, call its effect before the reveal, and learn to calibrate. Everything runs locally; nothing about you is collected.
This is the tool — a free calibration game. Watch the two β6 draws of beta-globin: the same position, one drastic (sickle cell), one mild (hemoglobin C). Every variant + effect is listed in full below (works without JavaScript). A native version, when it ships, adds offline use; it never gates the web.
Loading the game… If it does not start, the full variant guide below still works.
How to play. Press Start. A real amino-acid change appears — call its effect No / little, Mild, or Drastic (buttons or keys 1, 2, 3). The documented effect is revealed and your call is scored. Press Enter or Next to continue. There is no way to lose.
Why not every letter is drastic
A protein’s sequence is a recipe, but proteins are robust: many positions tolerate a swap with little change, and only certain letters at certain spots matter a lot. Reading “one letter changed” as “it’s broken” is misconception M08. This game trains calibration — and the clearest lesson is the two beta-globin draws at position β6: the same spot, one drastic, one mild.
The variants
| Protein | Change | Effect | What it does |
|---|---|---|---|
| Beta-globin HBB · P68871 | β6 Glu → Val | Drastic | Sickle-cell disease (both copies) — the hemoglobin sticks into fibres. |
| Beta-globin HBB · P68871 | β6 Glu → Lys | Mild | Hemoglobin C — same spot, different letter: usually mild or symptom-free. |
| CFTR CFTR · P13569 | Phe508 deleted (ΔF508) | Drastic | The most common cystic-fibrosis change; the protein misfolds. |
| Glucose-6-phosphate dehydrogenase G6PD · P11413 | Asn126 → Asp (A+) | No / little | A common variant with near-normal activity — most carriers never notice. |
| Aldehyde dehydrogenase 2 ALDH2 · P05091 | Glu504 → Lys (ALDH2*2) | Mild | The alcohol-flush letter — much lower activity; a real but conditional effect. |
| Melanocortin-1 receptor MC1R · Q01726 | Arg151 → Cys | No / little | A red-hair / fair-skin letter — a change in appearance, not a disease. |
| p53 TP53 · P04637 | Arg175 → His | Drastic | A cancer hotspot — cripples p53’s DNA-binding core. |
Methods & about
This is a teaching game, honest about being a simplification. Real variant effects depend on which copies you carry, background, and environment; the buckets here (no/little · mild · drastic) are lay summaries of well-documented cases, each verified before publishing. Structures are the real AlphaFold predictions fetched in your browser (shown for context; the exact residue is not highlighted, to avoid numbering confusion). The game keeps no score history, uses no accounts, and sends nothing anywhere. It is not a variant-effect predictor or a diagnostic.
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