Protein Structure, Molecular Mechanisms and Human Genetic Disease: Beyond the Loss-of-function Paradigm

Project Information

PROT-STRUCT-DISEASE

Grant agreement ID: 101001169

DOI

10.3030/101001169

EC signature date 20 January 2021

Start date 1 June 2021

End date 31 May 2026

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 000 000,00

EU contribution

€ 2 000 000,00

Coordinated by

THE UNIVERSITY OF EDINBURGH
United Kingdom

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Deliverables

Open Research Data Pilot (1)

Data Management Plan

Publications

Peer reviewed articles (15)

ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma

Author(s): Yuting Lu, Jana Travnickova, Mihaly Badonyi, Florian Rambow, Andrea Coates, Zaid Khan, Jair Marques, Laura C. Murphy, Pablo Garcia-Martinez, Richard Marais, Pakavarin Louphrasitthiphol, Alex H.Y. Chan, Christopher J. Schofield, Alex von Kriegsheim, Joseph A. Marsh, Valeria Pavet, Owen J. Sansom, Robert S. Illingworth, E. Elizabeth Patton
Published in: Cell Reports, Issue 43, 2024, Page(s) 114406, ISSN 2211-1247
Publisher: Cell Press
DOI: 10.1016/j.celrep.2024.114406

Structural insight into the function of human peptidyl arginine deiminase 6

Author(s): Jack P.C. Williams, Stephane Mouilleron, Rolando Hernandez Trapero, M. Teresa Bertran, Joseph A. Marsh, Louise J. Walport
Published in: Computational and Structural Biotechnology Journal, Issue 23, 2024, Page(s) 3258-3269, ISSN 2001-0370
Publisher: Elsevier
DOI: 10.1016/j.csbj.2024.08.019

Proteome-scale prediction of molecular mechanisms underlying dominant genetic diseases

Author(s): Mihaly Badonyi, Joseph A. Marsh
Published in: PLOS ONE, Issue 19, 2024, Page(s) e0307312, ISSN 1932-6203
Publisher: Public Library of Science
DOI: 10.1371/journal.pone.0307312

Loss-of-function, gain-of-function and dominant-negative mutations have profoundly different effects on protein structure

Author(s): Lukas Gerasimavicius, Benjamin J Livesey, Joseph A Marsh
Published in: Nature Communications, 2022, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-022-31686-6

<i>CDK4</i>loss-of-function mutations cause microcephaly and short stature

Author(s): Aitana Verdu Schlie, Andrea Leitch, Maria Izabel Arismendi, Colin Stok, Andrea Castro Leal, David A. Parry, Antonio Marcondes Lerario, Margaret E. Harley, Bruna Lucheze, Paula L. Carroll, Kamila I. Musialik, Julia M.T. Auer, Carol-Anne Martin, Lukas Gerasimavicius, Alan J. Quigley, Joya Emilie de Menezes Correia-Deur, Joseph A. Marsh, Martin A.M. Reijns, Anne K. Lampe, Andrew P. Jackson, Alexander
Published in: Genes &amp; Development, Issue 39, 2025, Page(s) 634-651, ISSN 0890-9369
Publisher: Cold Spring Harbor Laboratory Press
DOI: 10.1101/gad.352311.124

Deep mutational scanning quantifies DNA binding and predicts clinical outcomes of PAX6 variants

Author(s): Alexander F McDonnell, Marcin Plech, Benjamin J Livesey, Lukas Gerasimavicius, Liusaidh J Owen, Hildegard Nikki Hall, David R FitzPatrick, Joseph A Marsh, Grzegorz Kudla
Published in: Molecular Systems Biology, 2023, ISSN 1744-4292
Publisher: Nature Publishing Group
DOI: 10.1101/2023.07.25.550478

acmgscaler: An R package and Colab for standardised gene-level variant effect score calibration within the ACMG/AMP framework

Author(s): Mihaly Badonyi, Joseph A Marsh
Published in: Bioinformatics, 2026, ISSN 1367-4811
Publisher: Oxford University Press
DOI: 10.1101/2025.05.16.654507

Buffering of genetic dominance by allele-specific protein complex assembly

Author(s): Mihaly Badonyi, Joseph A Marsh
Published in: Science Advances, Issue 9, 2023, Page(s) eadf9845, ISSN 2375-2548
Publisher: American Association for the Advancement of Science
DOI: 10.1126/sciadv.adf9845

Correspondence between functional scores from deep mutational scans and predicted effects on protein stability

Author(s): Lukas Gerasimavicius, Benjamin J. Livesey, Joseph A. Marsh
Published in: Protein Science, Issue 32, 2023, Page(s) e4688, ISSN 1469-896X
Publisher: Wiley
DOI: 10.1002/pro.4688

Variant scoring tools for deep mutational scanning

Author(s): Hasan Çubuk, Xinyi Jin, Belinda Phipson, Joseph A Marsh, Alan F Rubin
Published in: Molecular Systems Biology, Issue 21, 2025, Page(s) 1293-1305, ISSN 1744-4292
Publisher: Nature Publishing Group
DOI: 10.1038/s44320-025-00137-x

Prevalence of loss-of-function, gain-of-function and dominant-negative mechanisms across genetic disease phenotypes

Author(s): Mihaly Badonyi, Joseph A. Marsh
Published in: Nature Communications, Issue 16, 2025, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-025-63234-3

Guidelines for releasing a variant effect predictor

Author(s): Benjamin J. Livesey, Mihaly Badonyi, Mafalda Dias, Jonathan Frazer, Sushant Kumar, Kresten Lindorff-Larsen, David M. McCandlish, Rose Orenbuch, Courtney A. Shearer, Lara Muffley, Julia Foreman, Andrew M. Glazer, Ben Lehner, Debora S. Marks, Frederick P. Roth, Alan F. Rubin, Lea M. Starita, Joseph A. Marsh
Published in: Genome Biology, Issue 26, 2025, ISSN 1474-760X
Publisher: Springer Science and Business Media LLC
DOI: 10.1186/s13059-025-03572-z

Protein structural context of cancer mutations reveals molecular mechanisms and candidate driver genes

Author(s): Diego Chillón-Pino, Mihaly Badonyi, Colin A. Semple, Joseph A. Marsh
Published in: Cell Reports, Issue 43, 2025, Page(s) 114905, ISSN 2211-1247
Publisher: Cell Press
DOI: 10.1016/j.celrep.2024.114905

Gain-of-function human <i>UNC93B1</i> variants cause systemic lupus erythematosus and chilblain lupus

Author(s): Clémence David, Carlos A. Arango-Franco, Mihaly Badonyi, Julien Fouchet, Gillian I. Rice, Blaise Didry-Barca, Lucie Maisonneuve, Luis Seabra, Robin Kechiche, Cécile Masson, Aurélie Cobat, Laurent Abel, Estelle Talouarn, Vivien Béziat, Caroline Deswarte, Katie Livingstone, Carle Paul, Gulshan Malik, Alison Ross, Jane Adam, Jo Walsh, Sathish Kumar, Damien Bonnet, Christine Bodemer, Brigitte Bade
Published in: Journal of Experimental Medicine, Issue 221, 2024, ISSN 0022-1007
Publisher: Rockefeller University Press
DOI: 10.1084/jem.20232066

Updated benchmarking of variant effect predictors using deep mutational scanning

Author(s): Benjamin J Livesey, Joseph A Marsh
Published in: Molecular Systems Biology, Issue 19, 2023, Page(s) e11474, ISSN 1744-4292
Publisher: Nature Publishing Group
DOI: 10.15252/msb.202211474