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Reveals novel proteins encoded in non-coding mRNA, suggesting new functional roles in genomics.
We report Cryptic Frame Mining, a computational-experimental method that systematically identifies stable, functional proteins from alternative reading frames in "non-coding" mRNA regions. Applied to human FGF21, we discovered P44, a 44-amino acid de novo protein with predicted coiled-coil structure and high-confidence AlphaFold models. P44 forms a putative receptor complex named the Ailtozin System. We also identified P28 and P19, two additional frameshift proteins. All sequences, structures, and confidence metrics are provided. This work demonstrates that supposedly silent genomic regions encode functional proteomes.
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Ailton Douglas de Souza Moreno (2026) studied this question.
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