SpliceSplit
One gene can make several different proteins by alternative splicing — mixing and matching its exons. It is tempting to picture a single chain that morphs into different shapes. That is not what happens: splicing builds different chains (different sequences), and each one folds to its own shape. In this game you compare two isoforms of a gene and pick the exon block that explains the difference. Everything runs locally; nothing about you is collected.
This is the tool — a small comparison game, no login, nothing tracked. Every gene and its isoforms are listed in full below (works without JavaScript).
Loading the game… If it does not start, the full isoform guide below still works.
How to play. Press Start. Read the two isoforms, then choose the exon block that differs between them (buttons or number keys 1–4). The answer is revealed with a short explanation. Press Enter or Next to continue.
Different chains, not one morphing
A gene is read as exons that can be joined in different combinations. Each combination is a different messenger RNA and therefore a different protein chain. Those chains can fold to very different shapes (like Bcl-xL vs Bcl-xS) or to almost the same shape with different regulation (like PKM1 vs PKM2). Either way it is not one identical chain refolding — that is the misconception this game targets (M10). AlphaFold’s 2026 expansion into isoforms is exactly about showing these different chains side by side.
The genes and their isoforms
| Gene | Isoform A | Isoform B | The differing exon block |
|---|---|---|---|
| BCL2L1 Q07817 | Bcl-xL (long) — anti-apoptotic full helical bundle (BH1–BH4) | Bcl-xS (short) — an alternative 5′ splice site removes the BH1–BH2 helices; pro-apoptotic | BH1–BH2 segment Two DIFFERENT chains from one gene, opposite jobs — Bcl-xS folds to its own shorter shape, it is not Bcl-xL rearranged. |
| PKM P14618 | PKM1 — constitutively active (muscle/brain) | PKM2 — allosterically regulated (by fructose-1,6-bisphosphate); prominent in cancer cells | Mutually-exclusive exon 9/10 segment (~aa 378–434) Here the fold is nearly the same — the swapped ~45-residue exon changes regulation, not gross shape. Still two different chains, not one morphing. |
| TPM1 (tropomyosin α-1) P09493 | Striated-muscle tropomyosin — one set of terminal exons | Smooth-muscle / non-muscle tropomyosin — alternative N- and C-terminal exons | The terminal exons (N- and C-terminal ends) The swapped exons are at the ends; the coiled-coil middle is shared. Different chains, gripping actin differently. |
Methods & about
This is a teaching game and honest about being a simplification: the isoform “blocks” are a coarse schematic of each gene’s alternatively-spliced regions, not exact exon coordinates. The examples are canonical — BCL2L1 (Bcl-xL/Bcl-xS, exon skipping; dramatically different function), PKM (PKM1/PKM2, mutually-exclusive exons; near-identical fold, different regulation), and TPM1 (tropomyosin, terminal-exon variants). Every isoform note is written by hand, not generated, and science-checked. No accounts, no storage, no servers.
Want to compare two structures yourself? Open FoldCompare or the free AlphaFold viewer. Everything we make is free and non-profit; learn more on the home page.