CNOT9 was first reported in relation to autosomal dominant complex neurodevelopmental disorder in 2023 (von Wintzingerode et al., PMID: 37092538). Phenotypic features reported in affected individuals include developmental delay, prominent speech delay, intellectual disability, seizures, anxiety, impulsivity, hyperactivity, and ophthalmological and skeletal abnormalities (PMID: 37092538).
Four de novo missense variants that have been reported in seven probands in one publication (PMID: 37092538) are included in this curation. Molecular modeling suggests that these variants can lead to reduced protein stability or impaired interaction with other proteins within the CCR4-NOT complex (PMID: 37092538). There is also experimental evidence such as biochemical and protein interaction (PMIDs: 30309886, 24768540).
In summary, there is limited evidence to support the gene-disease relationship between CNOT9 and autosomal dominant complex neurodevelopmental disorder. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on April 1, 2025 (SOP Version 11).
CNOT9 was first reported in relation to autosomal dominant complex neurodevelopmental disorder in 2023 (von Wintzingerode et al., 2023 PMID: 37092538). Phenotypic features reported in affected individuals include developmental delay, prominent speech delay, intellectual disability, seizures, anxiety, impulsivity, hyperactivity, and ophthalmological and skeletal abnormalities (PMID: 37092538).
Four de novo variants (missense) that have been reported in seven probands in one publication (PMID: 37092538) are included in this curation. Molecular modeling suggests that these variants can lead to reduced protein stability or impaired interaction with other proteins within the CCR4-NOT complex (PMID: 37092538). There is also experimental evidence such as biochemical and protein interaction (PMID: 30309886; 24768540).
In summary, there is limited evidence to support the gene-disease relationship between CNOT9 and autosomal dominant complex neurodevelopmental disorder. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the Intellectual Disability and Autism Gene Curation Expert Panel on April 1, 2025 (SOP Version 11).
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