Developmental Brain Disorder Gene Database

LoF Variant Gene

Gene
Search
Return to LoF Gene Listing Page

Tier

1

DDX3X

HGNC:2745 (protein-coding gene)

DEAD-box helicase 3 X-linked

Unique Cases:
81
Disorders:
ID, ASD, EP, ADHD, CP
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

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, Cerebral Palsy

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

Publications:

Lennox AL et. al., Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development., Neuron, 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
Suzuki T et. al., A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders., Ann Clin Transl Neurol, 2020
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021
Bowling KM et. al., Genomic diagnosis for children with intellectual disability and/or developmental delay., Genome Med, 2017
Elliott AM et. al., Genome-wide sequencing and the clinical diagnosis of genetic disease: The CAUSES study., HGG Adv, 2022
Fehlings DL et. al., Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy., Nat Genet, 2024
Wang Y et. al., Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy., Nat Med, 2024

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
Back To Top

Autism & Developmental Medicine Institute