{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lacoste J"],"funding":["Government of Ontario","NHGRI NIH HHS","Wyoming Affiliate of Susan G Komen Breast Cancer Foundation","National Institutes of Health","Cancer Prevention and Research Institute of Texas","NIGMS NIH HHS","Canadian Institutes of Health Research"],"pagination":["6725-6741.e13"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11568917"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["187(23)"],"pubmed_abstract":["Widespread sequencing has yielded thousands of missense variants predicted or confirmed as disease causing. This creates a new bottleneck: determining the functional impact of each variant-typically a painstaking, customized process undertaken one or a few genes and variants at a time. Here, we established a high-throughput imaging platform to assay the impact of coding variation on protein localization, evaluating 3,448 missense variants of over 1,000 genes and phenotypes. We discovered that mislocalization is a common consequence of coding variation, affecting about one-sixth of all pathogenic missense variants, all cellular compartments, and recessive and dominant disorders alike. Mislocalization is primarily driven by effects on protein stability and membrane insertion rather than disr"],"journal":["Cell"],"pubmed_title":["Pervasive mislocalization of pathogenic coding variants underlying human disorders."],"pmcid":["PMC11568917"],"funding_grant_id":["UM1 HG011989","RM1 HG010461","R35 GM122547","R35 GM137836","R35 GM133658"],"pubmed_authors":["Senft R","Shafqat-Abbasi H","Roth FP","Haghighi M","Ryder PV","Yi SS","Reno C","Lacoste J","Hao T","Xiong X","Taipale M","Segal D","Cimini BA","Nyirakanani C","Singh S","Calderwood MA","Lin ZY","McClain GG","Carpenter AE","Teelucksingh T","Hill DE","Qian WW","Miglietta E","Haider S","Vidal M","Sahni N","Murray RR","Peng J","Gingras AC"],"additional_accession":[]},"is_claimable":false,"name":"Pervasive mislocalization of pathogenic coding variants underlying human disorders.","description":"Widespread sequencing has yielded thousands of missense variants predicted or confirmed as disease causing. This creates a new bottleneck: determining the functional impact of each variant-typically a painstaking, customized process undertaken one or a few genes and variants at a time. Here, we established a high-throughput imaging platform to assay the impact of coding variation on protein localization, evaluating 3,448 missense variants of over 1,000 genes and phenotypes. We discovered that mislocalization is a common consequence of coding variation, affecting about one-sixth of all pathogenic missense variants, all cellular compartments, and recessive and dominant disorders alike. Mislocalization is primarily driven by effects on protein stability and membrane insertion rather than disr","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-06-06T13:56:49.208Z","creation":"2026-05-31T03:10:10.93Z"},"accession":"S-EPMC11568917","cross_references":{"pubmed":["39353438"],"doi":["10.1016/j.cell.2024.09.003"]}}