CNOT3 (HGNC: 7879) encodes the CCR4-NOT transcription complex subunit 3, which is a component of the CCR4-NOT complex. The protein plays as a global regulator of RNA polymerase II transcription. Genetic predisposition in CNOT3 have been observed in patients with ID/ASD (PMID: 31201375; 32720325; 31474762), T-cell acute lymphoblastic leukemia (PMID: 23263491), lung cancer (PMID: 31177396; PMID: 3053184), polyposis adenomas (PMID: 31231471); colorectal cancer (PMID: 2789937). Typical phenotypes of complex neurodevelopmental disorder (MONDO: 0100038) have been repeatedly observed across studies, and identical variants detected in unrelated probands inherited by autosomal dominant mechanism (HP:0000006). CNOT3 de novo missense and LOF variants, which are absent from gnomAD, have been found in patients from a DDD study (PMID: 31201375) or other study (PMID: 31474762) with identical clinical presentations of ID/ASD, hypotonia and dysmorphic features. Familial transmission of LOF variants have been observed in two families with history of ID (PMID: 32720325). Genetic evidence reached the max score of 12 points. There are no functional studies present in the literature. In summary, CNOT3 is definitively associated with complex neurodevelopmental disorder. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 08/24/2021 (SOP Version 8).
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.