DDX3X
DEAD-box helicase 3 X-linked, the group of DEAD-box helicases
Basic information
Region (hg38): X:41333347-41364472
Previous symbols: [ "DDX3" ]
Links
Phenotypes
GenCC
Source:
- intellectual disability, X-linked 102 (Definitive), mode of inheritance: XLR
- intellectual disability, X-linked 102 (Definitive), mode of inheritance: XL
- intellectual disability, X-linked 102 (Strong), mode of inheritance: XL
- X-linked syndromic intellectual disability (Definitive), mode of inheritance: XL
- Toriello-Carey syndrome (Supportive), mode of inheritance: AR
- X-linked intellectual disability-hypotonia-movement disorder syndrome (Supportive), mode of inheritance: XL
- intellectual disability, X-linked 102 (Definitive), mode of inheritance: XL
- X-linked syndromic intellectual disability (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Intellectual developmental disorder, X-linked, Snijders Blok type (Mental retardation, X-linked 102) | XL | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Musculoskeletal; Neurologic | 25533962; 26235985 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (451 variants)
- Intellectual disability, X-linked 102 (126 variants)
- Inborn genetic diseases (65 variants)
- Intellectual disability (15 variants)
- not specified (8 variants)
- DDX3X-related condition (7 variants)
- Neurodevelopmental disorder (5 variants)
- See cases (4 variants)
- Congenital cerebellar hypoplasia (2 variants)
- DDX3X-Related Disorder (2 variants)
- DDX3X-related X-linked intellectual disability (2 variants)
- Neurodevelopmental delay (2 variants)
- X-linked intellectual disability-hypotonia-movement disorder syndrome (2 variants)
- Rare genetic intellectual disability (2 variants)
- Global developmental delay (1 variants)
- Neurodevelopmental abnormality (1 variants)
- Intellectual disability, X-linked 102;Cerebellar vermis hypoplasia (1 variants)
- Autism;Intellectual disability (1 variants)
- Syndromic X-linked intellectual disability Claes-Jensen type (1 variants)
- DDX3X-Related Neurodevelopmental Disorder (1 variants)
- Marfanoid habitus and intellectual disability (1 variants)
- X-linked syndromic intellectual disability (1 variants)
- Delayed speech and language development;Global developmental delay;Microcephaly (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DDX3X gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 54 | 66 | ||||
| missense | 21 | 59 | 101 | 185 | ||
| nonsense | 36 | 45 | ||||
| start loss | 3 | |||||
| frameshift | 62 | 16 | 78 | |||
| inframe indel | 11 | |||||
| splice donor/acceptor (+/-2bp) | 15 | 11 | 29 | |||
| splice region ? | 1 | 3 | 7 | 19 | 7 | 37 |
| non coding ? | 11 | 63 | 35 | 109 | ||
| Total | 141 | 98 | 121 | 122 | 44 |
Highest pathogenic variant AF is 0.00000896
Variants in DDX3X
This is a list of pathogenic ClinVar variants found in the DDX3X region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| X-41333436-C-T | Likely benign (Aug 06, 2019) | |||
| X-41333711-G-C | Likely benign (Sep 29, 2019) | |||
| X-41333716-A-C | Likely benign (Aug 10, 2019) | |||
| X-41333721-AC-A | Likely benign (Aug 10, 2019) | |||
| X-41334181-G-A | Likely benign (Jul 27, 2018) | |||
| X-41334253-A-G | Pathogenic (Jan 06, 2024) | |||
| X-41334255-G-A | DDX3X-related disorder | Pathogenic (Jun 07, 2023) | ||
| X-41334255-G-C | Inborn genetic diseases | Pathogenic (Apr 17, 2017) | ||
| X-41334255-G-T | Intellectual disability, X-linked 102 | Pathogenic (Jan 24, 2024) | ||
| X-41334258-T-TC | DDX3X-Related Neurodevelopmental Disorder | Likely pathogenic (-) | ||
| X-41334270-G-A | Likely benign (Jul 19, 2022) | |||
| X-41334275-A-G | Uncertain significance (Jul 08, 2020) | |||
| X-41334279-G-A | Likely benign (Dec 08, 2023) | |||
| X-41334283-G-A | Uncertain significance (May 15, 2022) | |||
| X-41334290-A-G | Uncertain significance (Dec 01, 2023) | |||
| X-41334292-C-T | Intellectual disability | Pathogenic (Sep 10, 2020) | ||
| X-41334294-G-C | Intellectual disability, X-linked 102 | Benign (-) | ||
| X-41334298-G-C | Intellectual disability, X-linked 102 | Likely pathogenic (Nov 23, 2023) | ||
| X-41334299-T-A | Likely pathogenic (Dec 01, 2022) | |||
| X-41334306-C-G | not specified | Likely benign (Mar 12, 2024) | ||
| X-41334316-A-C | Likely benign (Dec 02, 2023) | |||
| X-41334316-A-G | Benign (Nov 09, 2021) | |||
| X-41334492-C-T | Benign (Jul 15, 2018) | |||
| X-41334493-C-T | Benign (Jul 15, 2018) | |||
| X-41334613-T-G | Likely benign (Aug 30, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DDX3X | protein_coding | protein_coding | ENST00000399959 | 17 | 31075 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000143 | 115149 | 0 | 1 | 115150 | 0.00000434 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.33 | 78 | 283 | 0.276 | 0.0000238 | 4371 |
| Missense in Polyphen | 6 | 74.692 | 0.080329 | 1334 | ||
| Synonymous | -0.675 | 98 | 89.9 | 1.09 | 0.00000712 | 1230 |
| Loss of Function | 4.65 | 0 | 25.2 | 0.00 | 0.00000186 | 458 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000399 | 0.0000399 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Multifunctional ATP-dependent RNA helicase. The ATPase activity can be stimulated by various ribo- and deoxynucleic acids indicative for a relaxed substrate specificity. In vitro can unwind partially double-stranded DNA with a preference for 5'- single-stranded DNA overhangs. Is involved in several steps of gene expression, such as transcription, mRNA maturation, mRNA export and translation. However, the exact mechanisms are not known and some functions may be specific for a subset of mRNAs. Involved in transcriptional regulation. Can enhance transcription from the CDKN1A/WAF1 promoter in a SP1-dependent manner. Found associated with the E-cadherin promoter and can down-regulate transcription from the promoter. Involved in regulation of translation initiation. Proposed to be involved in positive regulation of translation such as of cyclin E1/CCNE1 mRNA and specifically of mRNAs containing complex secondary structures in their 5'UTRs; these functions seem to require RNA helicase activity. Specifically promotes translation of a subset of viral and cellular mRNAs carrying a 5'proximal stem-loop structure in their 5'UTRs and cooperates with the eIF4F complex. Proposed to act prior to 43S ribosomal scanning and to locally destabilize these RNA structures to allow recognition of the mRNA cap or loading onto the 40S subunit. After association with 40S ribosomal subunits seems to be involved in the functional assembly of 80S ribosomes; the function seems to cover translation of mRNAs with structured and non-structured 5'UTRs and is independent of RNA helicase activity. Also proposed to inhibit cap-dependent translation by competetive interaction with EIF4E which can block the EIF4E:EIF4G complex formation. Proposed to be involved in stress response and stress granule assembly; the function is independent of RNA helicase activity and seems to involve association with EIF4E. May be involved in nuclear export of specific mRNAs but not in bulk mRNA export via interactions with XPO1 and NXF1. Also associates with polyadenylated mRNAs independently of NXF1. Associates with spliced mRNAs in an exon junction complex (EJC)-dependent manner and seems not to be directly involved in splicing. May be involved in nuclear mRNA export by association with DDX5 and regulating its nuclear location. Involved in innate immune signaling promoting the production of type I interferon (IFN-alpha and IFN-beta); proposed to act as viral RNA sensor, signaling intermediate and transcriptional coactivator. Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFNB induction, plays a role of scaffolding adapter that links IKBKE and IRF3 and coordinates their activation. Also found associated with IFNB promoters; the function is independent of IRF3. Can bind to viral RNAs and via association with MAVS/IPS1 and DDX58/RIG-I is thought to induce signaling in early stages of infection. Involved in regulation of apoptosis. May be required for activation of the intrinsic but inhibit activation of the extrinsic apoptotic pathway. Acts as an antiapoptotic protein through association with GSK3A/B and BIRC2 in an apoptosis antagonizing signaling complex; activation of death receptors promotes caspase-dependent cleavage of BIRC2 and DDX3X and relieves the inhibition. May be involved in mitotic chromosome segregation. Is an allosteric activator of CSNK1E, it stimulates CSNK1E-mediated phosphorylation of DVL2 and is involved in the positive regulation of canonical Wnt signaling (PubMed:23413191). {ECO:0000269|PubMed:16301996, ECO:0000269|PubMed:16818630, ECO:0000269|PubMed:17357160, ECO:0000269|PubMed:17667941, ECO:0000269|PubMed:18264132, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:18596238, ECO:0000269|PubMed:18628297, ECO:0000269|PubMed:18636090, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20375222, ECO:0000269|PubMed:20657822, ECO:0000269|PubMed:20837705, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:21730191, ECO:0000269|PubMed:21883093, ECO:0000269|PubMed:22034099, ECO:0000269|PubMed:22323517, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:23413191, ECO:0000269|PubMed:23478265}.;
- Disease
- DISEASE: Mental retardation, X-linked 102 (MRX102) [MIM:300958]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. MRX102 features include mild to severe intellectual disability, hypotonia, movement disorders, behavior problems, corpus callosum hypoplasia, and epilepsy. Additionally, patients manifest variable non-neurologic features such as joint hyperlaxity, skin pigmentary abnormalities, cleft lip and/or palate, hearing and visual impairment, and precocious puberty. {ECO:0000269|PubMed:26235985}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Viral carcinogenesis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);RIG-I-like Receptor Signaling;Neutrophil degranulation;TCR;Innate Immune System;Immune System;EGFR1;TNFalpha
(Consensus)
Recessive Scores
- pRec
- 0.338
Intolerance Scores
- loftool
- 0.0555
- rvis_EVS
- -0.12
- rvis_percentile_EVS
- 44.54
Haploinsufficiency Scores
- pHI
- 0.760
- hipred
- Y
- hipred_score
- 0.758
- ghis
- 0.686
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.694
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |
Mouse Genome Informatics
- Gene name
- Ddx3x
- Phenotype
- nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- ddx3xb
- Affected structure
- trunk
- Phenotype tag
- abnormal
- Phenotype quality
- curved ventral
Gene ontology
- Biological process
- translational initiation;chromosome segregation;extrinsic apoptotic signaling pathway via death domain receptors;response to virus;RNA secondary structure unwinding;positive regulation of gene expression;viral process;Wnt signaling pathway;negative regulation of translation;positive regulation of cell growth;negative regulation of cell growth;negative regulation of protein complex assembly;DNA duplex unwinding;positive regulation of interferon-beta production;stress granule assembly;intracellular signal transduction;mature ribosome assembly;positive regulation of apoptotic process;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;neutrophil degranulation;positive regulation of viral genome replication;innate immune response;positive regulation of translation;positive regulation of transcription by RNA polymerase II;positive regulation of translational initiation;cellular response to arsenic-containing substance;cellular response to osmotic stress;positive regulation of chemokine (C-C motif) ligand 5 production;positive regulation of protein serine/threonine kinase activity;positive regulation of canonical Wnt signaling pathway;intrinsic apoptotic signaling pathway;positive regulation of G1/S transition of mitotic cell cycle;protein localization to cytoplasmic stress granule;negative regulation of intrinsic apoptotic signaling pathway
- Cellular component
- extracellular region;nucleus;cytoplasm;mitochondrial outer membrane;cytosol;eukaryotic translation initiation factor 3 complex;cytoplasmic stress granule;nuclear speck;cytosolic small ribosomal subunit;secretory granule lumen;extracellular exosome;ficolin-1-rich granule lumen
- Molecular function
- DNA binding;RNA binding;GTPase activity;ATP-dependent DNA helicase activity;ATP-dependent RNA helicase activity;protein binding;ATP binding;transcription factor binding;poly(A) binding;eukaryotic initiation factor 4E binding;ATPase activity;nucleoside-triphosphatase activity;translation initiation factor binding;RNA strand annealing activity;RNA stem-loop binding;ribosomal small subunit binding;CTPase activity;protein serine/threonine kinase activator activity;cadherin binding;mRNA 5'-UTR binding