Phase separation as a missing mechanism for interpretation of disease mutations

B Tsang, I Pritišanac, SW Scherer, AM Moses… - Cell, 2020 - cell.com
It is unclear how disease mutations impact intrinsically disordered protein regions (IDRs),
which lack a stable folded structure. These mutations, while prevalent in disease, are …

Diverse molecular mechanisms underlying pathogenic protein mutations: beyond the loss-of-function paradigm

L Backwell, JA Marsh - Annual review of genomics and human …, 2022 - annualreviews.org
Most known disease-causing mutations occur in protein-coding regions of DNA. While some
of these involve a loss of protein function (eg, through premature stop codons or missense …

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

L Gerasimavicius, BJ Livesey, JA Marsh - Nature communications, 2022 - nature.com
Most known pathogenic mutations occur in protein-coding regions of DNA and change the
way proteins are made. Taking protein structure into account has therefore provided great …

AlphaFold heralds a data-driven revolution in biology and medicine

JM Thornton, RA Laskowski, N Borkakoti - Nature Medicine, 2021 - nature.com
AlphaFold heralds a data-driven revolution in biology and medicine | Nature Medicine Skip to
main content Thank you for visiting nature.com. You are using a browser version with limited …

DDMut: predicting effects of mutations on protein stability using deep learning

Y Zhou, Q Pan, DEV Pires… - Nucleic Acids …, 2023 - academic.oup.com
Understanding the effects of mutations on protein stability is crucial for variant interpretation
and prioritisation, protein engineering, and biotechnology. Despite significant efforts …

ProThermDB: thermodynamic database for proteins and mutants revisited after 15 years

R Nikam, A Kulandaisamy, K Harini… - Nucleic acids …, 2021 - academic.oup.com
ProThermDB is an updated version of the thermodynamic database for proteins and mutants
(ProTherm), which has∼ 31 500 data on protein stability, an increase of 84% from the …

Incomplete penetrance and variable expressivity: from clinical studies to population cohorts

R Kingdom, CF Wright - Frontiers in Genetics, 2022 - frontiersin.org
The same genetic variant found in different individuals can cause a range of diverse
phenotypes, from no discernible clinical phenotype to severe disease, even among related …

The genetics of asthma and the promise of genomics-guided drug target discovery

ZW El-Husseini, R Gosens, F Dekker… - The Lancet …, 2020 - thelancet.com
Asthma is an inflammatory airway disease that is estimated to affect 339 million people
globally. The symptoms of about 5–10% of patients with asthma are not adequately …

Genetic variation associated with condensate dysregulation in disease

SF Banani, LK Afeyan, SW Hawken, JE Henninger… - Developmental cell, 2022 - cell.com
A multitude of cellular processes involve biomolecular condensates, which has led to the
suggestion that diverse pathogenic mutations may dysregulate condensates. Although proof …

Folding and misfolding of human membrane proteins in health and disease: from single molecules to cellular proteostasis

JT Marinko, H Huang, WD Penn, JA Capra… - Chemical …, 2019 - ACS Publications
Advances over the past 25 years have revealed much about how the structural properties of
membranes and associated proteins are linked to the thermodynamics and kinetics of …