DDX6 Gene

DDX6 Gene

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">DDX6 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>DDX6</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>DEAD-Box Helicase 6</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>11p13</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1656</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>601834</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000110367</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P46193</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>p54, RCK, DDX6, HELR</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">G3BP1</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">GW182</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">DCP1/DCP2</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">CCR4-NOT</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">Ago2</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">FMRP</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">TDP-43</td>
<td>Indirect</td>
</tr>
<tr>
<td class="label">FUS</td>
<td>Indirect</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a"

DDX6 Gene

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">DDX6 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>DDX6</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>DEAD-Box Helicase 6</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>11p13</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1656</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>601834</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000110367</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P46193</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>p54, RCK, DDX6, HELR</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">G3BP1</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">GW182</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">DCP1/DCP2</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">CCR4-NOT</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">Ago2</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">FMRP</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">TDP-43</td>
<td>Indirect</td>
</tr>
<tr>
<td class="label">FUS</td>
<td>Indirect</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">3 edges</a></td>
</tr>
</table>

The DDX6 gene encodes DEAD-Box Helicase 6 (also known as p54, RCK, or DDX6), a member of the DEAD-box family of RNA helicases. DDX6 is a highly conserved ATP-dependent RNA helicase that plays central roles in RNA metabolism, including mRNA decay, translational repression, and the formation of RNA granules. DDX6 is a major component of processing bodies (P-bodies) and stress granules, which are cytoplasmic RNA-protein aggregates implicated in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), and other neurodegenerative diseases. [@ayache2015][@mochizuki2021]

Gene Information

Protein Structure

DDX6 is a 482-amino acid protein with a molecular weight of approximately 54 kDa. It contains the characteristic motifs of the DEAD-box helicase family:

Core Domains

• Motif I (AxxGxGKT): ATP binding
• Motif II (DEAD): ATP hydrolysis (helicase activity)
• Motif III: ATP-dependent RNA unwinding
• Motif IV: RNA binding
• Motif V: RNA binding
• Motif VI: ATP hydrolysis and helicase activity

Structural Features

• Two RecA-like helicase domains (N-terminal and C-terminal)
• Flexible linker between domains
• Multiple post-translational modification sites
• RGG-rich N-terminal region involved in protein-protein interactions

Cellular Functions

Processing Bodies (P-Bodies)

DDX6 is a central component of P-bodies, which are cytoplasmic foci involved in mRNA decay and translational repression:

• DDX6 recruits other P-body components including GW182, CCR4-NOT, and DCP1/DCP2
• DDX6 promotes mRNA decapping and 5'-to-3' decay
• DDX6 mediates translational repression through interaction with the miRNA pathway
• P-bodies serve as sites of mRNA storage and degradation
• DDX6 ATPase activity regulates P-body dynamics

Stress Granules

DDX6 is recruited to stress granules, which form in response to cellular stress:

• Stress granules contain translationally stalled mRNPs
• DDX6 interacts with G3BP1, TIA-1, and other stress granule markers
• DDX6 regulates stress granule assembly and dynamics
• ATPase-deficient DDX6 mutants alter stress granule behavior
• DDX6-containing stress granules can transition to pathological aggregates in disease

mRNA Decay and Translation Regulation

DDX6 participates in multiple mRNA regulatory pathways:

Decapping and Decay

• DDX6 promotes mRNA decapping through interaction with DCP1/DCP2
• Facilitates 5'-to-3' exonucleolytic decay
• DDX6 recruits the CCR4-NOT deadenylation complex

Translational Repression

• DDX6 blocks translation initiation by interfering with eIF4E function
• Interacts with P-bodies and represses translation
• Plays roles in miRNA-mediated gene silencing
• Can also promote translation in certain contexts

Role in the Nervous System

Neuronal Expression

DDX6 is widely expressed in the brain with high levels in:

• [Cortex](/brain-regions/cortex) — pyramidal neurons
• [Hippocampus](/brain-regions/hippocampus) — CA1 and CA3 pyramidal cells
• Cerebellum — Purkinje cells
• Spinal cord motor neurons
• Throughout the central and peripheral nervous system

Synaptic Function

In neurons, DDX6 localizes to:

• Dendritic shafts and spines
• Synaptic terminals
• RNA granules in dendrites

Local Protein Synthesis

Synaptic Plasticity

• Regulates translation of synaptic proteins
• Participates in long-term potentiation (LTP)
• Affects dendritic spine morphology
• Required for memory consolidation

Neuronal Stress Response

DDX6 participates in the neuronal stress response:

• Forms stress granules in response to oxidative stress
• Aggregates in pathological inclusions in neurodegenerative diseases
• May protect against proteotoxic stress
• Dysregulation leads to toxic gain-of-function

Disease Associations

Amyotrophic Lateral Sclerosis (ALS)

DDX6 is directly implicated in [ALS](/diseases/amyotrophic-lateral-sclerosis) pathogenesis:

• DDX6 is a major component of stress granules that become pathological in ALS
• Mutations in DDX6 have been identified in ALS and FTD patients
• DDX6-positive inclusions are found in motor neurons of ALS patients
• DDX6 aggregates colocalize with TDP-43 inclusions in most ALS cases
• DDX6 dysfunction may contribute to RNA metabolism defects in ALS
• DDX6 variants affect disease progression and phenotype

Frontotemporal Dementia (FTD)

DDX6 is involved in [FTD](/diseases/frontotemporal-dementia):

• DDX6-positive inclusions are found in some FTD cases
• DDX6 mutations cause familial FTD in some families
• DDX6 interacts with other FTD proteins including FUS and TDP-43
• DDX6 dysfunction may contribute to RNA dysregulation in FTD
• DDX6 is in the FTLD-U subtype with TDP-43 pathology

Spinocerebellar Ataxia

DDX6 is implicated in ataxia pathogenesis:

• DDX6 dysregulation contributes to cerebellar degeneration
• DDX6 mutations have been linked to SCA
• DDX6-containing granules may transport mutant proteins in SCA
• DDX6-mediated translational dysregulation affects Purkinje cell function

Fragile X Syndrome

DDX6 plays a role in [Fragile X Syndrome](/diseases/fragile-x-syndrome):

• DDX6 is regulated by FMRP (Fragile X mental retardation protein)
• DDX6 mediates translational dysregulation in FXS
• DDX6 levels are altered in FMRP knockout mice
• DDX6 may be a therapeutic target in FXS

Other Neurological Conditions

• Alzheimer's Disease: DDX6 may be involved in amyloid-mediated toxicity
• Huntington's Disease: DDX6 in stress granule formation with mutant huntingtin
• Multiple System Atrophy: DDX6 in glial cytoplasmic inclusions

Therapeutic Approaches

Direct Targeting

• Developing small molecules that modulate DDX6 helicase activity
• Antisense oligonucleotides to reduce toxic DDX6 aggregates
• CRISPR approaches to correct disease-causing mutations

Indirect Strategies

• Targeting stress granule formation pathways
• Modulating autophagy to clear DDX6 inclusions
• Enhancing RNA metabolism function

Research Directions

• Understanding DDX6 aggregation mechanisms in disease
• Developing DDX6-targeted therapeutics
• Biomarker development for DDX6-related disease
• Gene therapy approaches

Signaling and Interactions

Protein Interactions

Key Publications

See Also

• [DDX5 Gene](/genes/ddx5) — Related DEAD-box helicase
• [DDX3X Gene](/genes/ddx3x) — Related DEAD-box helicase in stress granules
• [TDP-43 Protein](/proteins/tdp-43) — RNA-binding protein in ALS/FTD
• [FUS Protein](/proteins/fus-protein) — Fused in sarcoma protein
• [Stress Granule Pathway](/mechanisms/stress-granule-pathway)
• [P-Body Pathway](/mechanisms/p-body-pathway)
• [ALS](/diseases/amyotrophic-lateral-sclerosis)
• [Frontotemporal Dementia](/diseases/frontotemporal-dementia)
• [Spinocerebellar Ataxia](/diseases/spinocerebellar-ataxia)
• [Synaptic Plasticity](/mechanisms/synaptic-plasticity)

External Links

• [NCBI Gene - DDX6](https://www.ncbi.nlm.nih.gov/gene/1656)
• [UniProt - P46193](https://www.uniprot.org/uniprot/P46193)
• [OMIM - 601834](https://www.omim.org/entry/601834)
• [GeneCards - DDX6](https://www.genecards.org/cgi-bin/carddisp.pl?gene=DDX6)

Pathway Diagram

The following diagram shows the key molecular relationships involving DDX6 Gene discovered through SciDEX knowledge graph analysis: