Cryptic Frame Mining Reveals a De Novo +1 Frameshift Protein System: P44 and the Ailtozin Complex

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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Publication Details

Journal
Zenodo (CERN European Organization for Nuclear Research)
Published
2026-05-29
DOI
https://doi.org/10.5281/zenodo.20436599
Primary Topic
Machine Learning in Bioinformatics
Type
preprint
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preprint

Cryptic Frame Mining Reveals a De Novo +1 Frameshift Protein System: P44 and the Ailtozin Complex

Ailton Douglas de Souza Moreno
Zenodo (CERN European Organization for Nuclear Research)
Machine Learning in Bioinformatics
preprint

Cryptic Frame Mining Reveals a De Novo +1 Frameshift Protein System: P44 and the Ailtozin Complex

Ailton Douglas de Souza Moreno
preprint en

Abstract

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.

Zenodo (CERN European Organization for Nuclear Research)
Quality Education
Machine Learning in Bioinformatics
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