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Dysfunction of the two intermediate dynein chains WDR34 and WDR60 causes Short Rib Thoracic Dystrophy (SRTD), a human skeletal chondrodysplasias with high lethality. However, individual protein functions are incompletely understood as complete loss of function of WDR34 or WDR60 is lethal in vertebrates and individuals with SRTD carry at least one putative hypomorphic missense allele. Gene knockout is therefore not suitable to study the effect of these human missense disease alleles. Therefore, using CRISPR single base editors, we recreate three different human disease missense alleles, including a novel WDR60 variant, p.Ala968Val identified in this study. Consistent with previous findings in the dynein-2 full loss of function models and patient fibroblasts, mutant cell lines show hedgehog signaling defects as well as disturbed retrograde IFT. Transcriptome analyses reveal differentially regulated expression of genes associated with various biological processes, including regulation of the actin cytoskeleton. Further, we observe differential regulation of genes associated with Golgi intracellular transport. In addition to providing cellular model systems enabling investigations of the effect of human SRTD disease alleles, our findings indicate non-ciliary functions for WDR34 and WDR60 in addition to the established roles as components of the retrograde IFT motor complex in cilia.<\/jats:p>","DOI":"10.1038\/s42003-026-10507-2","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T18:47:23Z","timestamp":1782931643000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Base editing-derived models of human WDR34 and WDR60 disease alleles replicate retrograde intraflagellar transport (IFT) and hedgehog signaling defects"],"prefix":"10.1038","volume":"9","author":[{"given":"Dinu","family":"Antony","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif Yilmaz","family":"G\u00fcle\u00e7","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Klawonn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeineb","family":"Bakey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Sch\u00fcle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwang-Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7757-4630","authenticated-orcid":false,"given":"Toni","family":"Cathomen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilona","family":"Skatulla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9274-8865","authenticated-orcid":false,"given":"Han G.","family":"Brunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian J.","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1714-6749","authenticated-orcid":false,"given":"Miriam","family":"Schmidts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"10507_CR1","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1038\/nrm3667","volume":"14","author":"AJ Roberts","year":"2013","unstructured":"Roberts, A. 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