IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-57510-5.html
   My bibliography  Save this article

Deep indel mutagenesis reveals the impact of amino acid insertions and deletions on protein stability and function

Author

Listed:
  • Magdalena Topolska

    (The Barcelona Institute of Science and Technology
    University Pompeu Fabra (UPF))

  • Antoni Beltran

    (The Barcelona Institute of Science and Technology)

  • Ben Lehner

    (The Barcelona Institute of Science and Technology
    University Pompeu Fabra (UPF)
    Institució Catalana de Recerca i estudis Avançats (ICREA)
    Wellcome Genome Campus)

Abstract

Amino acid insertions and deletions (indels) are an abundant class of genetic variants. However, compared to substitutions, the effects of indels on protein stability are not well understood. To better understand indels here we analyse new and existing large-scale deep indel mutagenesis (DIM) of structurally diverse proteins. The effects of indels on protein stability vary extensively among and within proteins and are not well predicted by existing computational methods. To address this shortcoming we present INDELi, a series of models that combine experimental or predicted substitution effects and secondary structure information to provide good prediction of the effects of indels on both protein stability and pathogenicity. Moreover, quantifying the effects of indels on protein-protein interactions suggests that insertions can be an important class of gain-of-function variants. Our results provide an overview of the impact of indels on proteins and a method to predict their effects genome-wide.

Suggested Citation

  • Magdalena Topolska & Antoni Beltran & Ben Lehner, 2025. "Deep indel mutagenesis reveals the impact of amino acid insertions and deletions on protein stability and function," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57510-5
    DOI: 10.1038/s41467-025-57510-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-57510-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-57510-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57510-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.