DDX3X

Chr XXLDXLR

DEAD-box helicase 3 X-linked

Also known as: CAP-Rf, DBX, DDX14, DDX3, HLP2, MRX102, MRXSSB

NCBI Gene: 1654ENSG00000215301UniProt: O00571OMIM: 300160

The protein encoded by this gene is a member of the large DEAD-box protein family, that is defined by the presence of the conserved Asp-Glu-Ala-Asp (DEAD) motif, and has ATP-dependent RNA helicase activity. This protein has been reported to display a high level of RNA-independent ATPase activity, and unlike most DEAD-box helicases, the ATPase activity is thought to be stimulated by both RNA and DNA. This protein has multiple conserved domains and is thought to play roles in both the nucleus and cytoplasm. Nuclear roles include transcriptional regulation, mRNP assembly, pre-mRNA splicing, and mRNA export. In the cytoplasm, this protein is thought to be involved in translation, cellular signaling, and viral replication. Misregulation of this gene has been implicated in tumorigenesis. This gene has a paralog located in the nonrecombining region of the Y chromosome. Pseudogenes sharing similarity to both this gene and the DDX3Y paralog are found on chromosome 4 and the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked syndromic, Snijders Blok typeMIM #300958
XLDXLR

Clinical highlights

Gene-disease validity (ClinGen)
X-linked syndromic intellectual disability · XLDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
155
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.12
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — DDX3X
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.12LOEUF
pLI 1.000
Z-score 4.65
OE 0.00 (0.00–0.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
4.33Z-score
OE missense 0.28 (0.23–0.33)
78 obs / 282.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.12)
0≤0.351.4
Missense OE?0.28 (0.23–0.33)
0≤0.61.4
Synonymous OE?1.09
0≤1.21.6
LoF obs/exp: 0 / 25.2Missense obs/exp: 78 / 282.9Syn Z: -0.68

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DDX3X · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients