DDX6

Chr 11

DEAD-box helicase 6

Also known as: HLR2, IDDILF, P54, RCK, Rck/p54

NCBI Gene: 1656ENSG00000110367UniProt: P26196

This gene encodes a member of the DEAD box protein family. The protein is an RNA helicase found in P-bodies and stress granules, and functions in translation suppression and mRNA degradation. It is required for microRNA-induced gene silencing. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Mar 2012]

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder with impaired language and dysmorphic facies
121
ClinVar variants
36
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— DDX6
⚡
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.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 68 VUS of 121 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.17LOEUF
pLI 1.000
Z-score 4.65
OE 0.04 (0.01–0.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.78Z-score
OE missense 0.34 (0.29–0.41)
89 obs / 260.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.04 (0.01–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.34 (0.29–0.41)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 1 / 27.2Missense obs/exp: 89 / 260.8Syn Z: 0.24

ClinVar Variant Classifications

121 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic5
VUS68
Likely Benign10
Benign6
Conflicting1
31
Pathogenic
5
Likely Pathogenic
68
VUS
10
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
5
26
0
31
Likely Pathogenic
0
3
2
0
5
VUS
3
49
15
1
68
Likely Benign
0
4
4
2
10
Benign
0
0
5
1
6
Conflicting
—1
Total361524121

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

View in ClinVar →

Protein Context — Lollipop Plot

DDX6 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DDX6-related intellectual disability

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeting PGE2 mediated senescent neuron improves tumor therapy.
Zhao J et al.·Neuro Oncol
2025
Oncogene RNA helicase DDX6 promotes the process of c-Myc expression in gastric cancer cells.
Taniguchi K et al.·Mol Carcinog
2018
Rab3B enhances the stabilization of DDX6 to promote lung adenocarcinoma aggressiveness.
Yao G et al.·Mol Med
2024
Systemic sclerosis pathogenesis: contribution of recent advances in genetics.
Orvain C et al.·Curr Opin Rheumatol
2020Review
RNA decay in processing bodies is indispensable for adipogenesis.
Maeda R et al.·Cell Death Dis
2021
The DEAD-box RNA-binding protein DDX6 regulates parental RNA decay for cellular reprogramming to pluripotency.
Kami D et al.·PLoS One
2018
Rare De Novo Missense Variants in RNA Helicase DDX6 Cause Intellectual Disability and Dysmorphic Features and Lead to P-Body Defects and RNA Dysregulation.
Balak C et al.·Am J Hum Genet
2019
DDX6 regulates sequestered nuclear CUG-expanded DMPK-mRNA in dystrophia myotonica type 1.
Pettersson OJ et al.·Nucleic Acids Res
2014
DEAD-Box Helicase DDX6 Facilitated RIG-I-Mediated Type-I Interferon Response to EV71 Infection.
Zhang R et al.·Front Cell Infect Microbiol
2021
Cytogenetic, molecular genetic, and clinical characteristics of acute myeloid leukemia with a complex karyotype.
Mrózek K·Semin Oncol
2008Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Posttraumatic Stress Disorder

Biomolecular Characteristics of Reminder-Focused Positive-Psychiatry

RECRUITING
NCT04529031Phase NAUniversity of California, Los AngelesStarted 2024-09-01
Reminder Focused Positive Psychiatryattentional control condition (group process)

External Resources

Links to major genomics databases and tools