Developmental Brain Disorder Gene Database

LoF Variant Gene

Gene

Return to LoF Gene Listing Page

Tier

1 DDX3X

HGNC:2745 (protein-coding gene)

DEAD-box helicase 3 X-linked

Unique Cases:: 71

Disorders:: ID, ASD, EP, ADHD

Last Updated:: May 1, 2021

Gene Summary:

DBD Genes Classification: DDX3X is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.

Gene Function: Multifunctional ATP-dependent RNA helicase (PubMed:17357160, PubMed:21589879, PubMed:31575075). The ATPase activity can be stimulated by various ribo-and deoxynucleic acids indicative for a relaxed substrate specificity (PubMed:29222110). In vitro can unwind partially double-stranded DNA with a preference for 5'-single-stranded DNA overhangs (PubMed:17357160, PubMed:21589879). Binds RNA G- quadruplex (rG4s) structures, including those located in the 5'-UTR of NRAS mRNA (PubMed:30256975). Involve... (Source: Uniprot)

Previous symbols: DDX3

Alias symbols: DBX, HLP2, DDX14, CAP-Rf

Chromosomal Location: Xp11.4

Genomic Coordinates: GRCh37:chrX:41192561-41223725; GRCh38:chrX:41333308-41364472

Associated Disorders: Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder

Predictive Scores:

HI Score (Decipher): 12.73

pLI (gnomAD): 1.00

LOEUF (gnomAD): 0.12

Classifications from External Sources:

SFARI Score (SFARI): 1

DDG2P Classification (DDG2P): Definitive

ClinGen Classification (ClinGen): Definitive1

GenCC Classification (GenCC): Definitive4 Strong1 Supportive2

Cases:

Publications:

Lennox AL et. al., Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development., Neuron, 2020

Wang T et. al., Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders., Nat Commun, 2020

Snijders Blok L et. al., Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling., Am J Hum Genet, 2015

Fieremans N et. al., Identification of Intellectual Disability Genes in Female Patients with a Skewed X-Inactivation Pattern., Hum Mutat, 2016

Iossifov I et. al., The contribution of de novo coding mutations to autism spectrum disorder., Nature, 2014

Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019

Guo H et. al., Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model., Mol Autism, 2018

Walker RF et. al., Clinical and genetic analysis of a rare syndrome associated with neoteny., Genet Med, 2018

Hu H et. al., Genetics of intellectual disability in consanguineous families., Mol Psychiatry, 2019

Kellaris G et. al., A hypomorphic inherited pathogenic variant in DDX3X causes male intellectual disability with additional neurodevelopmental and neurodegenerative features., Hum Genomics, 2018

External References:

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.

NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.

Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.

DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.

SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.

ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.

GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.

gnomAD

Developmental Brain Disorder Gene Database

LoF Variant Gene

Tier

1

DDX3X

HGNC:2745 (protein-coding gene)

DEAD-box helicase 3 X-linked

Gene Summary:

Predictive Scores:

12.73

1.00

0.12

Classifications from External Sources:

1

Definitive

Definitive1

Definitive4 Strong1 Supportive2

Cases:

Publications:

External References: