Protein destabilization underlies pathogenic missense mutations in ARID1B

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2024年2月12日

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Fanny Mermet-Meillon,
Samuele Mercan,
Beatrice Bauer-Probst,
Cyril Allard,
Melusine Bleu,
Keith Calkins,
Judith Knehr,
Marc Altorfer,
Ulrike Naumann,
Kathleen Sprouffske,
Louise Barys,
Fabian Sesterhenn,
Giorgio G. Galli

摘要

ARID1B is a SWI/SNF subunit frequently mutated in human Coffin–Siris syndrome (CSS) and it is necessary for proliferation of ARID1A mutant cancers. While most CSS ARID1B aberrations introduce frameshifts or stop codons, the functional consequence of missense mutations found in ARID1B is unclear. We here perform saturated mutagenesis screens on ARID1B and demonstrate that protein destabilization is the main mechanism associated with pathogenic missense mutations in patients with Coffin–Siris Syndrome.