DDX3X

Chr X

DEAD-box helicase 3 X-linked

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

The protein is an ATP-dependent RNA helicase that regulates transcription, mRNA splicing, mRNA export, and translation in both nuclear and cytoplasmic compartments. Loss-of-function mutations cause X-linked intellectual developmental disorder, Snijders Blok type, which can follow either X-linked dominant or recessive inheritance patterns. The gene is highly intolerant to loss-of-function variants, indicating that haploinsufficiency is the primary disease mechanism.

GeneReviewsResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismLOEUF 0.12
Clinical SummaryDDX3X
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Gene-Disease Validity (ClinGen)
X-linked syndromic intellectual disability · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — DDX3X
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 4.65
OE 0.00 (0.000.12)
Highly constrained

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

Missense Constraint
4.33Z-score
OE missense 0.28 (0.230.33)
78 obs / 282.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.12)
00.351.4
Missense OE0.28 (0.230.33)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 0 / 25.2Missense obs/exp: 78 / 282.9Syn Z: -0.68
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveDDX3X-related intellectual disabilityLOFmonoallelic_X_heterozygous
definitiveDDX3X-related intellectual developmental disorderOTHERXLR
DN
0.4784th %ile
GOF
0.4283th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.12

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗