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

Informazioni relative al progetto

PROT-STRUCT-DISEASE

ID dell’accordo di sovvenzione: 101001169

DOI

10.3030/101001169

Progetto chiuso

Data della firma CE 20 Gennaio 2021

Data di avvio 1 Giugno 2021

Data di completamento 31 Maggio 2026

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 2 000 000,00

Contributo UE

€ 2 000 000,00

Coordinato da

THE UNIVERSITY OF EDINBURGH
United Kingdom

CORDIS fornisce collegamenti ai risultati finali pubblici e alle pubblicazioni dei progetti ORIZZONTE.

I link ai risultati e alle pubblicazioni dei progetti del 7° PQ, così come i link ad alcuni tipi di risultati specifici come dataset e software, sono recuperati dinamicamente da .OpenAIRE .

Risultati finali

Open Research Data Pilot (1)

Data Management Plan

Pubblicazioni

Peer reviewed articles (22)

ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma

Autori: 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
Pubblicato in: Cell Reports, Numero 43, 2024, Pagina/e 114406, ISSN 2211-1247
Editore: Cell Press
DOI: 10.1016/j.celrep.2024.114406

Structural extension of the human exocyst is enabled by a minimal interface

Autori: Haonan D. Xu, Mihaly Badonyi, Marilyn Paul, Watanyoo Sopipong, Stuart A. MacGowan, Joseph A. Marsh, David H. Murray
Pubblicato in: Structure, Numero 34, 2026, Pagina/e 870-879.e5, ISSN 0969-2126
Editore: Cell Press
DOI: 10.1016/j.str.2026.02.004

Assessing variant effect predictors and disease mechanisms in intrinsically disordered proteins

Autori: Mohamed Fawzy, Joseph A. Marsh
Pubblicato in: PLOS Computational Biology, Numero 21, 2025, Pagina/e e1013400, ISSN 1553-7358
Editore: Public Library of Science (PLoS)
DOI: 10.1371/journal.pcbi.1013400

Structural insight into the function of human peptidyl arginine deiminase 6

Autori: Jack P.C. Williams, Stephane Mouilleron, Rolando Hernandez Trapero, M. Teresa Bertran, Joseph A. Marsh, Louise J. Walport
Pubblicato in: Computational and Structural Biotechnology Journal, Numero 23, 2024, Pagina/e 3258-3269, ISSN 2001-0370
Editore: Elsevier
DOI: 10.1016/j.csbj.2024.08.019

Proteome-scale prediction of molecular mechanisms underlying dominant genetic diseases

Autori: Mihaly Badonyi, Joseph A. Marsh
Pubblicato in: PLOS ONE, Numero 19, 2024, Pagina/e e0307312, ISSN 1932-6203
Editore: Public Library of Science
DOI: 10.1371/journal.pone.0307312

Mechanistic modeling of recessive disease through allelic integration of variant effects

Autori: Hasan Çubuk, Marcin Plech, Vahid Aslanzadeh, Marie Zikanova, Vaclava Skopova, Stanislav Kmoch, Yuxin Shen, Joseph A. Marsh, Grzegorz Kudla
Pubblicato in: Cell Systems, Numero 17, 2026, Pagina/e 101595, ISSN 2405-4712
Editore: Elsevier BV
DOI: 10.1016/j.cels.2026.101595

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

Autori: Lukas Gerasimavicius, Benjamin J Livesey, Joseph A Marsh
Pubblicato in: Nature Communications, 2022, ISSN 2041-1723
Editore: Nature Publishing Group
DOI: 10.1038/s41467-022-31686-6

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

Autori: 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
Pubblicato in: Genes &amp; Development, Numero 39, 2025, Pagina/e 634-651, ISSN 0890-9369
Editore: Cold Spring Harbor Laboratory Press
DOI: 10.1101/gad.352311.124

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

Autori: Alexander F McDonnell, Marcin Plech, Benjamin J Livesey, Lukas Gerasimavicius, Liusaidh J Owen, Hildegard Nikki Hall, David R FitzPatrick, Joseph A Marsh, Grzegorz Kudla
Pubblicato in: Molecular Systems Biology, 2023, ISSN 1744-4292
Editore: 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

Autori: Mihaly Badonyi, Joseph A Marsh
Pubblicato in: Bioinformatics, 2026, ISSN 1367-4811
Editore: Oxford University Press
DOI: 10.1101/2025.05.16.654507

A structure-guided approach to noncoding variant evaluation for transcription factor binding using AlphaFold 3

Autori: Lukas Gerasimavicius, Simon C Biddie, Joseph A Marsh
Pubblicato in: Nucleic Acids Research, Numero 54, 2026, ISSN 0305-1048
Editore: Oxford University Press
DOI: 10.1093/nar/gkaf1417

Complementary Roles of Structure and Variant Effect Predictors in RyR1 Clinical Interpretation

Autori: Rolando Hernández Trapero, Mihaly Badonyi, Lukas Gerasimavicius, Joseph A. Marsh
Pubblicato in: Human Mutation, Numero 2025, 2025, ISSN 1059-7794
Editore: John Wiley & Sons Inc.
DOI: 10.1155/humu/1834898

Buffering of genetic dominance by allele-specific protein complex assembly

Autori: Mihaly Badonyi, Joseph A Marsh
Pubblicato in: Science Advances, Numero 9, 2023, Pagina/e eadf9845, ISSN 2375-2548
Editore: 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

Autori: Lukas Gerasimavicius, Benjamin J. Livesey, Joseph A. Marsh
Pubblicato in: Protein Science, Numero 32, 2023, Pagina/e e4688, ISSN 1469-896X
Editore: Wiley
DOI: 10.1002/pro.4688

Variant scoring tools for deep mutational scanning

Autori: Hasan Çubuk, Xinyi Jin, Belinda Phipson, Joseph A Marsh, Alan F Rubin
Pubblicato in: Molecular Systems Biology, Numero 21, 2025, Pagina/e 1293-1305, ISSN 1744-4292
Editore: 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

Autori: Mihaly Badonyi, Joseph A. Marsh
Pubblicato in: Nature Communications, Numero 16, 2025, ISSN 2041-1723
Editore: Nature Publishing Group
DOI: 10.1038/s41467-025-63234-3

Guidelines for releasing a variant effect predictor

Autori: 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
Pubblicato in: Genome Biology, Numero 26, 2025, ISSN 1474-760X
Editore: Springer Science and Business Media LLC
DOI: 10.1186/s13059-025-03572-z

Dominant-negative effects of Weaver syndrome-associated EZH2 variants

Autori: Orla Deevy, Jingjing Li, Craig Monger, Francesca Matrà, Ellen Tuck, Molly Davies, Mihaly Badonyi, Maeve Boyce, Emma J. Doyle, Karsten Hokamp, Darragh Nimmo, Simona Rodighiero, Qi Zhang, Chen Davidovich, Joseph A. Marsh, Diego Pasini, Eric Conway, Adrian P. Bracken
Pubblicato in: Genes &amp; Development, Numero 39, 2025, Pagina/e 1355-1376, ISSN 0890-9369
Editore: Cold Spring Harbor Laboratory Press
DOI: 10.1101/gad.351884.124

Disease-associated genetic variants can cause missense effects in tissue-specific protein isoforms

Autori: Giovanna Weykopf, Mihaly Badonyi, Elias T. Friman, Jasmine Minh Hang Nguyen, Alexis Ioannou, Benjamin J. Livesey, Audrey Coutts, Elizabeth F. Hird, Murray Wham, Chloe M. Stanton, Veronique Vitart, Jing Su, Lee Murphy, J. Kenneth Baillie, Mark D. Gorrell, Joseph A. Marsh, Wendy A. Bickmore, Simon C. Biddie
Pubblicato in: Nature Communications, Numero 17, 2026, ISSN 2041-1723
Editore: Nature Publishing Group
DOI: 10.1038/s41467-026-74280-w

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

Autori: Diego Chillón-Pino, Mihaly Badonyi, Colin A. Semple, Joseph A. Marsh
Pubblicato in: Cell Reports, Numero 43, 2025, Pagina/e 114905, ISSN 2211-1247
Editore: Cell Press
DOI: 10.1016/j.celrep.2024.114905

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

Autori: 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
Pubblicato in: Journal of Experimental Medicine, Numero 221, 2024, ISSN 0022-1007
Editore: Rockefeller University Press
DOI: 10.1084/jem.20232066

Updated benchmarking of variant effect predictors using deep mutational scanning

Autori: Benjamin J Livesey, Joseph A Marsh
Pubblicato in: Molecular Systems Biology, Numero 19, 2023, Pagina/e e11474, ISSN 1744-4292
Editore: Nature Publishing Group
DOI: 10.15252/msb.202211474