Submission Details

The DDX3X gene is located on chromosome X at Xp11.4 and encodes the DEAD-box helicase 3 X-linked protein. This protein is a member of the DEAD-box ATP-dependent RNA helicases. As a regulator of Wnt-β-catenin signaling, DDX3X plays an important role in embryonic development. DDX3X is also thought to play roles in transcription, translation, and cellular signaling. DDX3X was first reported in relation to DDX3X-related X-linked syndromic intellectual disability in 2015 (26235985: Snijders Blok et al. 2015; 25533962: Deciphering Developmental Disorders Study 2015). More than 35 unique variants, including missense and predicted null variants, have been reported in humans (26235985:Snijders Blok et al. 2015). Evidence supporting this gene-disease relationship includes case-level and experimental data. Variants in this gene were curated in six affected females from two publications (26235985: Snijders Blok et al. 2015; 30174453: Carneiro et al. 2018). All variant occurred de novo. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. Haploinsufficiency appears to be the mechanism of disease in affected females. This gene-disease association is supported by animal models showing disrupted embryonic development and embryonic lethality and functional alteration studies demonstrating impaired Wnt-β-catenin signaling following gene knockdown (23413191: Cruciat et al. 2013; 27179789: Chen et al. 2017). In summary,the DDX3X gene is definitively associated with DDX3X-related X-linked syndromic intellectual disability.

PubMed IDs:

26235985 30174453 23413191 27179789 28554332 27159028

Assertion Criteria:

Click here to view assertion criteria

https://clinicalgenome.org/site/assets/files/2165/gene_curation_sop_version_6_aug_2018_final.pdf

Submitter Submitted Date:

10/15/2020

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).

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