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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
DDX23
DEAD-box helicase 23
Chromosome 12 Β· 12q13.12
NCBI Gene: 9416Ensembl: ENSG00000174243.12HGNC: HGNC:17347UniProt: B3KY11
163PubMed Papers
20Diseases
0Drugs
5Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
R-loop processinghelicase activityRNA bindingU4/U6 x U5 tri-snRNP complexdengue diseaseglobal developmental delay with speech and behavioral abnormalitiesNeurodevelopmental disorderIMAGe syndrome
✦AI Summary

DDX23 (DEAD-box helicase 23) is a multifunctional RNA helicase with primary roles in pre-mRNA splicing and innate antiviral immunity. In splicing, DDX23 functions as a spliceosomal component whose phosphorylation by SRPK2 is required for B complex formation 1. DDX23 interacts directly with SR protein SRSF1, with its N-terminal RS-like domain mediating spliceosome incorporation and the transition from pre-B to B spliceosome complexes 2. Beyond splicing, DDX23 suppresses incorrect R-loops formed during transcription 3. DDX23 functions as an evolutionarily conserved dsRNA sensor that translocates from nucleus to cytoplasm upon viral detection, forming complexes with TRIF or MAVS to activate NF-ΞΊB and IRF3 signaling during innate immune responses 4. In viral infections, DDX23 negatively regulates FMDV IRES-dependent translation and replication, though the virus degrades DDX23 via 3C proteinase 5. Clinically, elevated DDX23 m6A methylation promotes pancreatic ductal adenocarcinoma progression and gemcitabine resistance through PI3K/Akt signaling activation 6. Additionally, pharmacological promotion of SDC4/DDX23 complex formation induces hepatocellular carcinoma genomic instability 7. These findings establish DDX23 as a multivalent regulator of RNA metabolism and immunity with therapeutic relevance in cancer and viral diseases.

Sources cited
1
DDX23 phosphorylation by SRPK2 is required for spliceosomal B complex formation
PMID: 18425142
2
DDX23 suppresses incorrect R-loops formed during transcription
PMID: 28076779
3
General spliceosome mechanism providing context for DDX23's splicing function
PMID: 31794245
4
DDX23 interacts with SRSF1 through its N-terminal RS-like domain and is essential for pre-B to B spliceosome transition
PMID: 38743621
5
DDX23 is an evolutionarily conserved dsRNA sensor that translocates to cytoplasm and interacts with TRIF/MAVS during innate immune responses
PMID: 31620127
6
DDX23 negatively regulates FMDV IRES-dependent translation and replication but is degraded by viral 3C proteinase
PMID: 33255534
7
DDX23 mRNA m6A methylation by METTL3 promotes pancreatic cancer progression and gemcitabine resistance via PI3K/Akt signaling
PMID: 36977668
8
SDC4/DDX23 complex formation induces hepatocellular carcinoma genomic instability and inhibits migration
PMID: 33990545
9
DDX23 is a DExH/D-box helicase involved in innate immune activation against viral infections
PMID: 36006669
Disease Associationsβ“˜20
dengue diseaseOpen Targets
0.37Weak
global developmental delay with speech and behavioral abnormalitiesOpen Targets
0.37Weak
Neurodevelopmental disorderOpen Targets
0.34Weak
Abnormal facial shapeOpen Targets
0.27Weak
bilateral perisylvian polymicrogyriaOpen Targets
0.27Weak
Failure to thriveOpen Targets
0.27Weak
fetal growth restrictionOpen Targets
0.27Weak
IMAGe syndromeOpen Targets
0.27Weak
Motor delayOpen Targets
0.27Weak
genetic disorderOpen Targets
0.19Weak
complex neurodevelopmental disorderOpen Targets
0.18Weak
developmental disorder of mental healthOpen Targets
0.18Weak
Abruptio PlacentaeOpen Targets
0.14Weak
neurodegenerative diseaseOpen Targets
0.12Weak
Intellectual disabilityOpen Targets
0.12Weak
neurodevelopmental disorder with visual defects and brain anomaliesOpen Targets
0.12Weak
alcohol drinkingOpen Targets
0.11Weak
hypertensionOpen Targets
0.09Suggestive
Increased blood pressureOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.07Suggestive
Pathogenic Variants5
NM_004818.3(DDX23):c.1722C>A (p.Asn574Lys)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 574
NM_004818.3(DDX23):c.2437C>T (p.Arg813Cys)Likely pathogenic
Congenital bilateral perisylvian syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 813
NM_004818.3(DDX23):c.2131A>G (p.Lys711Glu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 711
NM_004818.3(DDX23):c.2127_2132del (p.Asn709_Leu710del)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 709
NM_004818.3(DDX23):c.1912C>T (p.Arg638Cys)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 638
View on ClinVar β†—
Related Genes
GCFC2Protein interaction100%SNRNP200Protein interaction100%SF3B2Protein interaction100%SNRPGProtein interaction100%SF3A2Protein interaction100%SNRPA1Protein interaction100%
Tissue Expression6 tissues
Lung
100%
Ovary
94%
Liver
91%
Brain
85%
Heart
65%
Bone Marrow
57%
Gene Interaction Network
Click a node to explore
DDX23GCFC2SNRNP200SF3B2SNRPGSF3A2SNRPA1
PROTEIN STRUCTURE
Preparing viewer…
PDB4NHO Β· 2.00 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.41Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.31 [0.23–0.41]
RankingsWhere DDX23 stands among ~20K protein-coding genes
  • #2,748of 20,598
    Most Researched163 Β· top quartile
  • #3,494of 5,498
    Most Pathogenic Variants5
  • #2,127of 17,882
    Most Constrained (LOEUF)0.41 Β· top quartile
Genes detectedDDX23
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
RNA Splicing by the Spliceosome.
PMID: 31794245
Annu Rev Biochem Β· 2020
1.00
2
METTL3 enhances pancreatic ductal adenocarcinoma progression and gemcitabine resistance through modifying DDX23 mRNA N6 adenosine methylation.
PMID: 36977668
Cell Death Dis Β· 2023
0.90
3
SRSF1 interactome determined by proximity labeling reveals direct interaction with spliceosomal RNA helicase DDX23.
PMID: 38743621
Proc Natl Acad Sci U S A Β· 2024
0.80
4
Syndromic neurodevelopmental disorder associated with de novo variants in DDX23.
PMID: 34050707
Am J Med Genet A Β· 2021
0.72
5
The DDX23 Negatively Regulates Translation and Replication of Foot-and-Mouth Disease Virus and Is Degraded by 3C Proteinase.
PMID: 33255534
Viruses Β· 2020
0.70