VIPAS39 was first reported in relation to autosomal recessive arthrogryposis, renal dysfunction, and cholestasis 2 (ARC) in 2010 (Cullinane AR, et al. ,2010, PMID: 20190753). The classical presentation of ARC includes congenital joint contractures, renal tubular dysfunction, and cholestasis. Additional features include ichthyosis, central nervous system malformation, platelet anomalies, and severe failure to thrive. At least 13 unique variants (mostly nonsense but also frameshift, splicing, start loss, and missense) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 9 probands in 4 publications (PMIDs: 20190753, 22753090, 23002115, 23636179). This gene-disease relationship is supported by its interaction with VPS33B (PMID: 20190753) and their function as part of a complex that interacts with an active form of RAB11A involved in apical membrane protein sorting, the alteration in mIMCD-3 cells confirming the role of VIPAS39 in regulating apical-basolateral polarity in the kidney consistent with the renal dysfunction seen in patients (PMID: 20190753), a zebrafish model recapitulating biliary abnormalities (PMID: 20190753), and a mouse model with collagen abnormalities identified in skin fibroblasts and tendons consistent with the characteristic ARC features of ichthyosis, arthrogryposis, osteopenia and bone fractures (PMID: 27435297). In summary VIPAS39 is definitively associated with autosomal recessive arthrogryposis, renal dysfunction, and cholestasis 2.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.