{"doi":"10.1073/pnas.2105228119","title":"A dominant negative variant of <i>RAB5B</i> disrupts maturation of surfactant protein B and surfactant protein C","abstract":"Significance The Rab5 GTPase functions in early endosome (EE) fusion in the endocytic pathway. Here, we propose that RAB5B also has a noncanonical vesicular fusion function in the regulated secretion pathway that produces mature surfactant proteins SP-B and SP-C in the lung. This function was revealed from investigation of a proband with interstitial lung disease suggestive of a surfactant dysfunction disorder who carried a de novo Asp136His variant in the RAB5B gene. Our modeling in C. elegans provided information on the genetic and cell biological mechanism, and analyses of proband and normal lung biopsies suggested a function for RAB5B and EEs in surfactant protein processing/trafficking. This work indicates that RAB5B p.Asp136His causes a surfactant dysfunction disorder.","journal":"Proceedings of the National Academy of Sciences","year":2022,"id":247975,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9606,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":273848,"name":"Jiehong Pan","orcid":"0000-0003-2384-6845","position":1,"is_corresponding":false},{"id":886665,"name":"David R. 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