{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:30:42Z","timestamp":1787567442655,"version":"build-2736575974"},"reference-count":46,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01HL167046"],"award-info":[{"award-number":["R01HL167046"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R01HL167046"],"award-info":[{"award-number":["R01HL167046"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["F31HL162483-01A1"],"award-info":[{"award-number":["F31HL162483-01A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"award":["F31HL162483-01A1"],"award-info":[{"award-number":["F31HL162483-01A1"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (\n                    <jats:italic>CFTR<\/jats:italic>\n                    ). Though most people with CF have one or two copies of the \u0394F508 mutation, there are hundreds of other distinct CF mutations that vary in their mechanistic effects and response to therapeutics. Endogenous chaperones are known to have divergent effects on the druggability of CF variants. Nevertheless, it remains unclear how this proteostatic modulation is related to the underlying mechanistic effects of distinct classes of CF mutations. Here, we survey the effects of a previously discovered effector (calnexin, CANX) on the expression and pharmacological rescue of 232 CF variants using deep mutational scanning. We find that CANX is generally required for robust plasma membrane expression of the CFTR protein, particularly for CF variants that perturb its second nucleotide-binding domain. CANX also appears to be critical for the pharmacological rescue of CF variants with poor basal expression. Though corrector selectivity is generally dictated by the properties of mutations, we find that CANX enhances the sensitivity of CF variants within a domain-swapped region of membranes spanning domain 2 to the type III corrector VX-445. Overall, mutagenic trends suggest CANX modulates the later stages of CFTR assembly and disproportionately affects variants bearing mutations within the C-terminal domains. Interestingly, we find that the loss of CANX results in widespread perturbations of CF variant interactomes and that the proteostatic effects of CANX are generally decoupled from changes in CFTR activity. Together, our findings reveal how the proteostasis machinery may shape the variant-specific effects of corrector molecules.\n                  <\/jats:p>","DOI":"10.7554\/elife.107180","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T15:30:26Z","timestamp":1753975826000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.107180","source":"Crossref","is-referenced-by-count":0,"title":["General trends in the calnexin-dependent expression and pharmacological rescue of clinical CFTR variants"],"prefix":"10.7554","volume":"14","author":[{"given":"Austin","family":"Tedman","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02dqehb95","id-type":"ROR","asserted-by":"publisher"}],"name":"The James Tarpo Jr. and Margaret Tarpo Department of Chemistry, Purdue University","place":["West Lafayette, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9654-6611","authenticated-orcid":true,"suffix":"III","given":"John A","family":"Olson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02vm5rt34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Vanderbilt University","place":["Nashville, United States"]},{"id":[{"id":"https:\/\/ror.org\/02vm5rt34","id-type":"ROR","asserted-by":"publisher"}],"name":"Program in Chemical and Physical Biology, Vanderbilt University","place":["Nashville, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-2999","authenticated-orcid":true,"given":"Minsoo","family":"Kim","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02vm5rt34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Vanderbilt University","place":["Nashville, United States"]},{"id":[{"id":"https:\/\/ror.org\/02vm5rt34","id-type":"ROR","asserted-by":"publisher"}],"name":"Program in Chemical and Physical Biology, Vanderbilt University","place":["Nashville, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Catherine","family":"Foye","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Emory University School of Medicine","place":["Atlanta, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"JaNise J","family":"Jackson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Emory University School of Medicine","place":["Atlanta, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0572-330X","authenticated-orcid":true,"given":"Eli F","family":"McDonald","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02vm5rt34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Vanderbilt University","place":["Nashville, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1238-987X","authenticated-orcid":true,"given":"Andrew G","family":"McKee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01kg8sb98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Indiana University","place":["Bloomington, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Karen","family":"Noguera","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01kg8sb98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Indiana University","place":["Bloomington, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Charles P","family":"Kuntz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02dqehb95","id-type":"ROR","asserted-by":"publisher"}],"name":"The James Tarpo Jr. and Margaret Tarpo Department of Chemistry, Purdue University","place":["West Lafayette, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Jens","family":"Meiler","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02vm5rt34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Vanderbilt University","place":["Nashville, United States"]},{"id":[{"id":"https:\/\/ror.org\/03s7gtk40","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Drug Discovery, Leipzig University","place":["Leipzig, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Kathryn E","family":"Oliver","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Emory University School of Medicine","place":["Atlanta, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4363-6116","authenticated-orcid":true,"given":"Lars","family":"Plate","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02vm5rt34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Vanderbilt University","place":["Nashville, United States"]},{"id":[{"id":"https:\/\/ror.org\/02vm5rt34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological Sciences, Vanderbilt University","place":["Nashville, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0955-7633","authenticated-orcid":true,"given":"Jonathan P","family":"Schlebach","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02dqehb95","id-type":"ROR","asserted-by":"publisher"}],"name":"The James Tarpo Jr. and Margaret Tarpo Department of Chemistry, Purdue University","place":["West Lafayette, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1016\/j.jcf.2024.02.006","type":"journal-article","article-title":"In vitro modulator responsiveness of 655 CFTR variants found in people with cystic fibrosis","volume":"23","author":"Bihler","year":"2024","journal-title":"Journal of Cystic Fibrosis"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2414768121","type":"journal-article","article-title":"Ribosomal frameshifting selectively modulates the assembly, function, and pharmacological rescue of a misfolded CFTR variant","volume":"121","author":"Carmody","year":"2024","journal-title":"PNAS"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/0092-8674(90)90148-8","type":"journal-article","article-title":"Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis","volume":"63","author":"Cheng","year":"1990","journal-title":"Cell"},{"key":"bib4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037682","type":"journal-article","article-title":"A chaperone trap contributes to the onset of cystic fibrosis","volume":"7","author":"Coppinger","year":"2012","journal-title":"PLOS ONE"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"3174","DOI":"10.1021\/acsinfecdis.0c00500","type":"journal-article","article-title":"Comparative multiplexed interactomics of SARS-CoV-2 and homologous coronavirus nonstructural proteins identifies unique and shared host-cell dependencies","volume":"6","author":"Davies","year":"2020","journal-title":"ACS Infectious Diseases"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"5242","DOI":"10.1128\/MCB.25.12.5242-5252.2005","type":"journal-article","article-title":"Most F508del-CFTR is targeted to degradation at an early folding checkpoint and independently of calnexin","volume":"25","author":"Farinha","year":"2005","journal-title":"Molecular and Cellular Biology"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1126\/science.ade2216","type":"journal-article","article-title":"Molecular structures reveal synergistic rescue of \u0394508 CFTR by Trikafta modulators","volume":"378","author":"Fiedorczuk","year":"2022","journal-title":"Science"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/S0014-5793(01)02561-3","type":"journal-article","article-title":"Green fluorescent protein\u2010based halide indicators with improved chloride and iodide affinities","volume":"499","author":"Galietta","year":"2001","journal-title":"FEBS Letters"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1083\/jcb.200808124","type":"journal-article","article-title":"N-glycans are direct determinants of CFTR folding and stability in secretory and endocytic membrane traffic","volume":"184","author":"Glozman","year":"2009","journal-title":"The Journal of Cell Biology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"13477","DOI":"10.1074\/jbc.RA118.003192","type":"journal-article","article-title":"Correcting the F508del-CFTR variant by modulating eukaryotic translation initiation factor 3-mediated translation initiation","volume":"293","author":"Hutt","year":"2018","journal-title":"The Journal of Biological Chemistry"},{"key":"bib11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052442","type":"journal-article","article-title":"Proximity profiling of the CFTR interaction landscape in response to orkambi","volume":"23","author":"Iazzi","year":"2022","journal-title":"International Journal of Molecular Sciences"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.105242","type":"journal-article","article-title":"Elexacaftor\/VX-445-mediated CFTR interactome remodeling reveals differential correction driven by mutation-specific translational dynamics","volume":"299","author":"Kim","year":"2023","journal-title":"The Journal of Biological Chemistry"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.166955","type":"journal-article","article-title":"Co-translational folding of the first transmembrane domain of ABC-transporter CFTR is supported by assembly with the first cytosolic domain","volume":"433","author":"Kleizen","year":"2021","journal-title":"Journal of Molecular Biology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"4322","DOI":"10.1111\/febs.15330","type":"journal-article","article-title":"Calnexin cycle - structural features of the ER chaperone system","volume":"287","author":"Kozlov","year":"2020","journal-title":"The FEBS Journal"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1111\/tra.12358","type":"journal-article","article-title":"N-Glycan-based ER molecular chaperone and protein quality control system: The Calnexin binding cycle","volume":"17","author":"Lamriben","year":"2016","journal-title":"Traffic"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/gm404","type":"journal-article","article-title":"A yeast phenomic model for the gene interaction network modulating CFTR-\u0394F508 protein biogenesis","volume":"4","author":"Louie","year":"2012","journal-title":"Genome Medicine"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1038\/ncb2090","type":"journal-article","article-title":"Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition","volume":"12","author":"Luciani","year":"2010","journal-title":"Nature Cell Biology"},{"key":"bib18","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx183","type":"journal-article","article-title":"A platform for functional assessment of large variant libraries in mammalian cells","volume":"45","author":"Matreyek","year":"2017","journal-title":"Nucleic Acids Research"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E21-11-0578","type":"journal-article","article-title":"Distinct proteostasis states drive pharmacologic chaperone susceptibility for cystic fibrosis transmembrane conductance regulator misfolding mutants","volume":"33","author":"McDonald","year":"2022","journal-title":"Molecular Biology of the Cell"},{"key":"bib20","doi-asserted-by":"publisher","DOI":"10.3390\/biom12030471","type":"journal-article","article-title":"Structural comparative modeling of multi-domain F508del CFTR","volume":"12","author":"McDonald","year":"2022","journal-title":"Biomolecules"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"2128","DOI":"10.1021\/acschembio.3c00310","type":"journal-article","article-title":"CFTR folding: From structure and proteostasis to cystic fibrosis personalized medicine","volume":"18","author":"McDonald","year":"2023","journal-title":"ACS Chemical Biology"},{"key":"bib22","type":"software","article-title":"CANX_KD_CFTR_Rosetta_Models","volume-title":"Software Heritage","author":"McDonald","year":"2025","unstructured":"McDonald EF. 2025. CANX_KD_CFTR_Rosetta_Models. Software Heritage. swh:1:rev:64f9d4cc0a33118681b7e069d6d9b6b458a6bd6e. https:\/\/archive.softwareheritage.org\/swh:1:dir:ef2ae60cbb6e5f688b2c5d4b7b0ae551473d89d7;origin=https:\/\/github.com\/emcd173\/CANX_KD_CFTR_Rosetta_Models;visit=swh:1:snp:109c8bfcfd00f542687fe2d928c25b9864864ffa;anchor=swh:1:rev:64f9d4cc0a33118681b7e069d6d9b6b458a6bd6e."},{"key":"bib23","doi-asserted-by":"publisher","DOI":"10.1101\/2024.07.10.602964","type":"preprint","article-title":"Proteostasis landscapes of cystic fibrosis variants reveals drug response vulnerability","volume-title":"bioRxiv","author":"McDonald","year":"2025"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.chembiol.2023.05.001","type":"journal-article","article-title":"General trends in the effects of VX-661 and VX-445 on the plasma membrane expression of clinical CFTR variants","volume":"30","author":"McKee","year":"2023","journal-title":"Cell Chemical Biology"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","type":"journal-article","article-title":"Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele","volume":"381","author":"Middleton","year":"2019","journal-title":"The New England Journal of Medicine"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1016\/j.bbamcr.2008.04.002","type":"journal-article","article-title":"Role of calnexin in the ER quality control and productive folding of CFTR; differential effect of calnexin knockout on wild-type and \u0394F508 CFTR","volume":"1783","author":"Okiyoneda","year":"2008","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Cell Research"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"5236","DOI":"10.1172\/JCI124282","type":"journal-article","article-title":"Slowing ribosome velocity restores folding and function of mutant CFTR","volume":"129","author":"Oliver","year":"2019","journal-title":"The Journal of Clinical Investigation"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1038\/nature15729","type":"journal-article","article-title":"\u2206F508 CFTR interactome remodelling promotes rescue of cystic fibrosis","volume":"528","author":"Pankow","year":"2015","journal-title":"Nature"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay7505","type":"journal-article","article-title":"Probing biophysical sequence constraints within the transmembrane domains of rhodopsin by deep mutational scanning","volume":"6","author":"Penn","year":"2020","journal-title":"Science Advances"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"L23","DOI":"10.1152\/ajplung.00426.2012","type":"journal-article","article-title":"Efficient delivery of RNA interference oligonucleotides to polarized airway epithelia in vitro","volume":"305","author":"Ramachandran","year":"2013","journal-title":"American Journal of Physiology-Lung Cellular and Molecular Physiology"},{"key":"bib31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2010612118","type":"journal-article","article-title":"Positive epistasis between disease-causing missense mutations and silent polymorphism with effect on mRNA translation velocity","volume":"118","author":"Rauscher","year":"2021","journal-title":"PNAS"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"4570","DOI":"10.1091\/mbc.e08-04-0357","type":"journal-article","article-title":"Assembly and misassembly of cystic fibrosis transmembrane conductance regulator: folding defects caused by deletion of F508 occur before and after the calnexin-dependent association of membrane spanning domain (MSD) 1 and MSD2","volume":"19","author":"Rosser","year":"2008","journal-title":"Molecular Biology of the Cell"},{"key":"bib33","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.86581","type":"journal-article","article-title":"Analysis of cystic fibrosis-associated P67L CFTR illustrates barriers to personalized therapeutics for orphan diseases","volume":"1","author":"Sabusap","year":"2016","journal-title":"JCI Insight"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100598","type":"journal-article","article-title":"The CFTR P67L variant reveals a key role for N-terminal lasso helices in channel folding, maturation, and pharmacologic rescue","volume":"296","author":"Sabusap","year":"2021","journal-title":"The Journal of Biological Chemistry"},{"key":"bib35","type":"software","article-title":"RP-dms-analysis","volume-title":"Software Heritage","author":"schebachlab","year":"2022","unstructured":"schebachlab. 2022. RP-dms-analysis. Software Heritage. swh:1:rev:bf029f0b56c850e0b0a4a71f4e7706268531bf49. https:\/\/archive.softwareheritage.org\/swh:1:dir:388ef21c875a9607d0fc42e9d4a1b355c85a6c37;origin=https:\/\/github.com\/schebachlab\/RP-dms-analysis;visit=swh:1:snp:c1b86387681f11d045bc7d2e23945189e52e27fd;anchor=swh:1:rev:bf029f0b56c850e0b0a4a71f4e7706268531bf49."},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1038\/ng.2745","type":"journal-article","article-title":"Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene","volume":"45","author":"Sosnay","year":"2013","journal-title":"Nature Genetics"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1056\/NEJMoa1709846","type":"journal-article","article-title":"Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del","volume":"377","author":"Taylor-Cousar","year":"2017","journal-title":"The New England Journal of Medicine"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2024.168591","type":"journal-article","article-title":"The folding pathway of ABC transporter CFTR: Effective and robust","volume":"436","author":"van der Sluijs","year":"2024","journal-title":"Journal of Molecular Biology"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1091\/mbc.E14-04-0935","type":"journal-article","article-title":"From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations","volume":"27","author":"Veit","year":"2016","journal-title":"Molecular Biology of the Cell"},{"key":"bib40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002462","type":"journal-article","article-title":"Ribosomal stalk protein silencing partially corrects the \u0394F508-CFTR functional expression defect","volume":"14","author":"Veit","year":"2016","journal-title":"PLOS Biology"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11070643","type":"journal-article","article-title":"A precision medicine approach to optimize modulator therapy for rare CFTR folding mutants","volume":"11","author":"Veit","year":"2021","journal-title":"Journal of Personalized Medicine"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1002\/cyto.a.22275","type":"journal-article","article-title":"A novel fluorescent sensor for measurement of CFTR function by flow cytometry","volume":"83","author":"Vijftigschild","year":"2013","journal-title":"Cytometry. Part A"},{"key":"dataset1","type":"dataset","article-title":"General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants","volume-title":"NCBI","author":"Schlebach","year":"2025","unstructured":"Schlebach J. 2025. General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants. NCBI. https:\/\/www.ncbi.nlm.nih.gov\/search\/all\/?term=PRJNA1244365. PRJNA1244365."},{"key":"dataset2","type":"dataset","article-title":"General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants - DDA","volume-title":"PRIDE","author":"Plate","year":"2025","unstructured":"Plate L. 2025. General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants - DDA. PRIDE. https:\/\/www.ebi.ac.uk\/pride\/archive\/projects\/PXD061664. PXD061664."},{"key":"dataset3","doi-asserted-by":"publisher","DOI":"10.17632\/ksfmxv8zts.1","type":"dataset","article-title":"General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants","volume-title":"Mendeley Data","author":"Tedman","year":"2025","unstructured":"Tedman A, Olson J, Kim M, Foye C, Jackson J, McDonald E, McKee A, Noguera K, Kuntz C, Meiler J, Oliver K, Plate L, Schlebach J. 2025. General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants. Mendeley Data."},{"key":"dataset4","type":"dataset","article-title":"General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants \u2013 DIA","volume-title":"PRIDE","author":"Plate","year":"2025","unstructured":"Plate L. 2025. General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants \u2013 DIA. PRIDE. https:\/\/www.ebi.ac.uk\/pride\/archive\/projects\/PXD066492. PXD066492."}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/107180\/elife-107180-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/107180\/elife-107180-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/107180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:14:25Z","timestamp":1787562865000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/107180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,11]]},"references-count":46,"alternative-id":["10.7554\/eLife.107180"],"URL":"https:\/\/doi.org\/10.7554\/elife.107180","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.04.03.647093","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2025.04.03.647093","asserted-by":"object"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.107180.3","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.107180.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.107180.2","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"PRJNA1244365","asserted-by":"subject"},{"id-type":"accession","id":"PXD061664","asserted-by":"subject"},{"id-type":"doi","id":"10.17632\/ksfmxv8zts.1","asserted-by":"subject"},{"id-type":"accession","id":"PXD066492","asserted-by":"subject"},{"id-type":"uri","id":"https:\/\/archive.softwareheritage.org\/swh:1:dir:ef2ae60cbb6e5f688b2c5d4b7b0ae551473d89d7;origin=https:\/\/github.com\/emcd173\/CANX_KD_CFTR_Rosetta_Models;visit=swh:1:snp:109c8bfcfd00f542687fe2d928c25b9864864ffa;anchor=swh:1:rev:64f9d4cc0a33118681b7e069d6d9b6b458a6bd6e","asserted-by":"subject"},{"id-type":"uri","id":"https:\/\/archive.softwareheritage.org\/swh:1:dir:388ef21c875a9607d0fc42e9d4a1b355c85a6c37;origin=https:\/\/github.com\/schebachlab\/RP-dms-analysis;visit=swh:1:snp:c1b86387681f11d045bc7d2e23945189e52e27fd;anchor=swh:1:rev:bf029f0b56c850e0b0a4a71f4e7706268531bf49","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,11]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP107180"}}