DDX53

Chr X

DEAD-box helicase 53

Also known as: CAGE, CT26

This gene encodes a DEAD-box helicase that participates in ATP-dependent RNA unwinding. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq
DNmechanismLOEUF 0.85
Clinical SummaryDDX53
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.66) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
76 unique Pathogenic / Likely Pathogenic· 98 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.85LOEUF
pLI 0.662
Z-score 1.74
OE 0.00 (0.000.85)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
0.01Z-score
OE missense 1.00 (0.901.11)
240 obs / 240.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.85)
00.351.4
Missense OE1.00 (0.901.11)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 0 / 3.5Missense obs/exp: 240 / 240.2Syn Z: -1.07
DN
0.74top 25%
GOF
0.6247th %ile
LOF
0.3746th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic71
Likely Pathogenic5
VUS98
Likely Benign14
Benign11
Conflicting1
71
Pathogenic
5
Likely Pathogenic
98
VUS
14
Likely Benign
11
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
71
0
71
Likely Pathogenic
1
1
3
0
5
VUS
4
78
16
0
98
Likely Benign
0
9
0
5
14
Benign
0
6
0
5
11
Conflicting
1
Total5949010200

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DDX53 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC