The OTUD5 gene is located on chromosome X at Xp11.23 and encodes a lysine-48/lysine-63 linkage-specific deubiquitinase. OTUD5 was first reported in relation to X-linked multiple congenital anomalies-neurodevelopmental syndrome in 2021 (Tripolszki et al.,PMID: 33131077). This disorder is characterized by characteristic craniofacial features, intellectual disability and global developmental delays, poor growth and with some individuals presenting with cardiac, skeletal, and genitourinary anomalies. The disorder has a very variable presentation. At least 11 unique variants (10 missense, 1 inframe deletion) have been reported in 12 probands in five publications (PMIDs: 33523931, 33131077, 35143101, 38037881, 33748114) and are included in this curation. This gene-disease relationship is supported by biochemical function studies, protein-protein interactions, and functional alterations in patient derived cells (PMIDs: 23827681, 28343629, 33523931). The mechanism of pathogenicity appears to be hypomorphic variants that are predominantly missense. In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date July 19, 2024 (SOP Version 10).
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.