Atlas of Genetics and Cytogenetics in Oncology and Haematology

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DHX9 (DEAH (Asp-Glu-Ala-His) box polypeptide 9)

Written2009-07Frédéric Guénard, Francine Durocher
Cancer Genomics Laboratory, Oncology, Molecular Endocrinology Research Centre, CRCHUL, CHUQ, Laval University, Québec, G1V 4G2, Canada

(Note : for Links provided by Atlas : click)


Other aliasDDX9
LocusID (NCBI) 1660
Atlas_Id 44879
Location 1q25.3  [Link to chromosome band 1q25]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


Description The gene spans 48.5 kb and is composed of 27 exons.
Transcription Transcription start is 163 bp upstream of first ATG of the DHX9 ORF. The translation start site is located in exon 2 and there is a sole isoform ubiquitously expressed.
Pseudogene DHX9 pseudogene (DHX9P) is located at 13q22.


  Structure of DHX9. dsRBD, double-stranded RNA binding domain; RGG, arginine and glycine-rich region; NTD, nuclear transport domain.
Description Monomeric 140 kDa protein. Human DHX9 is 1270 amino acids. It contains an helicase catalytic domain flanked by two double-stranded RNA binding domains (dsRBD) at the N-terminus and an RGG-box at the C terminus. A bidirectional nuclear transport domain is located at the C terminus.
Expression All tissues tested, ubiquitous expression.
Localisation DHX9 shuttles between the nucleus and the cytoplasm.
Function DHX9 is a nucleic-acid helicase that unwinds double-stranded DNA and RNA in a nucleotide dependent manner. It acts as a transcriptional coactivator which stimulates transcription by interacting with the transcriptional coactivator CBP/p300, the breast cancer protein BRCA1, the RNA polymerase II and has an important role in the assembly of STAT6 transcriptosome.
DHX9 plays a role in regulating chromatin structure by interacting physically and functionally with topoisomerase IIa.
It mediates the attachment of nuclear ribonucleoprotein complexes to actin filaments, which may be related to RNA processing and transport. DHX9 interacts with the survival motor neuron which plays a role in the assembly and regeneration of small nuclear ribonucleoproteins and spliceosomes.
DHX9 acts as a nuclear shuttle protein promoting the export of mRNA transcripts through binding to TAP and HAP95.
In the cytoplasm, DHX9 is preferentially associated with actively translating polyribosomes and is necessary for efficient translation of RNAs that contain a highly structured 5'UTR.
DHX9 might be necessary for maintaining genomic stability as it plays a role in promoting the DNA processing function of WRN. Overexpression of a truncated DHX9 peptide prevents normal BRCA1 function, such as BRCA1 association with nuclear foci following DNA damage. DHX9 associates with gH2AX after DNA damage, suggesting a role for DHX9 in DNA repair.
DHX9 is also necessary for early embryonic development in mice.
Homology Sequence analysis revealed that DHX9 contains seven helicase core motifs that are conserved among the DEX[D/H] helicase superfamily. DHX9 is highly conserved among man, cow, mouse, worm, and fruit fly.


Note DHX9 truncating mutations were reported to affect the interaction with BRCA1 and RNA polymerase II, and to result in decreased transcriptional activity of BRCA1.
In mammals, DHX9-knockout mice are embryonic lethal for homozygous DHX9 mutants. DHX9 is thus necessary for early embryonic development in mice. It was also suggested that DHX9 is required for the survival and differentiation of embryonic ectoderm.
DHX9 maps to chromosome 1q25 near a major susceptibility locus for prostate cancer.

Implicated in

Entity Lung cancer
Note DHX9 is over-expressed in tumor samples compared to normal lung tissues. There was a tendency for higher expression levels in small cell lung cancer compared to non-small cell carcinomas.
Prognosis There was no correlation with tumor stage and survival.
Entity Breast cancer
Note Involvement of DHX9 in breast cancer susceptibility was analyzed in a cohort of breast cancer individuals from non-BRCA1/BRCA2 French Canadian families. This study did not identify any deleterious truncating mutation or aberrant splicing in the DHX9 gene. It was concluded that studies on much bigger cohorts are needed to fully evaluate the association of variants identified with breast cancer risk.
Entity Systemic lupus erythematosus (SLE)
Note Anti-DHX9 is a new serologic marker for SLE. The production of anti-DHX9 may depend on a process restricted to early SLE, or it may be highly sensitive to treatment.
Disease Systemic lupus erythematosus (SLE) is a largely genetically based disease in which environmental factors are also involved. SLE is an autoimmune disease characterized by autoantibody production and involvement of multiple organ systems. Variable manifestations and outcome reflect the clinical heterogeneity of the disease. It is characterized by acute and chronic inflammation of various tissues of the body including joints, kidneys, mucous membranes, and blood vessel walls.
Prognosis Among patients with SLE, anti-DHX9 was common in young patients and at an early stage of the disease.


Aromatic residues are required for RNA helicase A mediated transactivation.
Aratani S, Fujii R, Fujita H, Fukamizu A, Nakajima T.
Int J Mol Med. 2003 Aug;12(2):175-80.
PMID 12851713
The nuclear import of RNA helicase A is mediated by importin-alpha3.
Aratani S, Oishi T, Fujita H, Nakazawa M, Fujii R, Imamoto N, Yoneda Y, Fukamizu A, Nakajima T.
Biochem Biophys Res Commun. 2006 Feb 3;340(1):125-33.
PMID 16375861
A functional interaction between RHA and Ubc9, an E2-like enzyme specific for Sumo-1.
Argasinska J, Zhou K, Donnelly RJ, Hay RT, Lee CG.
J Mol Biol. 2004 Jul 30;341(1):15-25.
PMID 15312759
Nuclear DNA helicase II (RNA helicase A) interacts with Werner syndrome helicase and stimulates its exonuclease activity.
Friedemann J, Grosse F, Zhang S.
J Biol Chem. 2005 Sep 2;280(35):31303-13. Epub 2005 Jul 1.
PMID 15995249
A Role of RNA Helicase A in cis-Acting Transactivation Response Element-mediated Transcriptional Regulation of Human Immunodeficiency Virus Type 1.
Fujii R, Okamoto M, Aratani S, Oishi T, Ohshima T, Taira K, Baba M, Fukamizu A, Nakajima T.
J Biol Chem. 2001 Feb 23;276(8):5445-51. Epub 2000 Nov 28.
PMID 11096080
Genetic sequence variations of BRCA1-interacting genes AURKA, BAP1, BARD1 and DHX9 in French Canadian Families with high risk of breast cancer.
Guenard F, Labrie Y, Ouellette G, Joly Beauparlant C, Durocher F.
J Hum Genet. 2009;54(3):152-61. Epub 2009 Feb 6.
PMID 19197335
RNA helicase A is necessary for translation of selected messenger RNAs.
Hartman TR, Qian S, Bolinger C, Fernandez S, Schoenberg DR, Boris-Lawrie K.
Nat Struct Mol Biol. 2006 Jun;13(6):509-16. Epub 2006 May 7.
PMID 16680162
ZIC2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A.
Ishiguro A, Ideta M, Mikoshiba K, Chen DJ, Aruga J.
J Biol Chem. 2007 Mar 30;282(13):9983-95. Epub 2007 Jan 23.
PMID 17251188
The human RNA helicase A (DDX9) gene maps to the prostate cancer susceptibility locus at chromosome band 1q25 and its pseudogene (DDX9P) to 13q22, respectively.
Lee CG, Eki T, Okumura K, Nogami M, Soares Vda C, Murakami Y, Hanaoka F, Hurwitz J.
Somat Cell Mol Genet. 1999 Jan;25(1):33-9.
PMID 10925702
The p53 target protein Wig-1 binds hnRNP A2/B1 and RNA Helicase A via RNA.
Prahl M, Vilborg A, Palmberg C, Jornvall H, Asker C, Wiman KG.
FEBS Lett. 2008 Jun 25;582(15):2173-7. Epub 2008 Jun 2.
PMID 18519039
RNA helicase A interacts with RISC in human cells and functions in RISC loading.
Robb GB, Rana TM.
Mol Cell. 2007 May 25;26(4):523-37.
PMID 17531811
Association of RNA helicase a with human immunodeficiency virus type 1 particles.
Roy BB, Hu J, Guo X, Russell RS, Guo F, Kleiman L, Liang C.
J Biol Chem. 2006 May 5;281(18):12625-35. Epub 2006 Mar 8.
PMID 16527808
Overexpression of a protein fragment of RNA helicase A causes inhibition of endogenous BRCA1 function and defects in ploidy and cytokinesis in mammary epithelial cells.
Schlegel BP, Starita LM, Parvin JD.
Oncogene. 2003 Feb 20;22(7):983-91.
PMID 12592385
Specific interaction between RNA helicase A and Tap, two cellular proteins that bind to the constitutive transport element of type D retrovirus.
Tang H, Wong-Staal F.
J Biol Chem. 2000 Oct 20;275(42):32694-700.
PMID 10924507
RNA helicase A interacts with nuclear factor kappaB p65 and functions as a transcriptional coactivator.
Tetsuka T, Uranishi H, Sanda T, Asamitsu K, Yang JP, Wong-Staal F, Okamoto T.
Eur J Biochem. 2004 Sep;271(18):3741-51.
PMID 15355351
Oncoprotein EWS-FLI1 activity is enhanced by RNA helicase A.
Toretsky JA, Erkizan V, Levenson A, Abaan OD, Parvin JD, Cripe TP, Rice AM, Lee SB, Uren A.
Cancer Res. 2006 Jun 1;66(11):5574-81.
PMID 16740692
Characterization of RNA helicase A as component of STAT6-dependent enhanceosome.
Valineva T, Yang J, Silvennoinen O.
Nucleic Acids Res. 2006;34(14):3938-46. Epub 2006 Aug 12.
PMID 16914450
Analysis of the RNA helicase A gene in human lung cancer.
Wei X, Pacyna-Gengelbach M, Schluns K, An Q, Gao Y, Cheng S, Petersen I.
Oncol Rep. 2004 Jan;11(1):253-8.
PMID 14654934
A novel shuttle protein binds to RNA helicase A and activates the retroviral constitutive transport element.
Westberg C, Yang JP, Tang H, Reddy TR, Wong-Staal F.
J Biol Chem. 2000 Jul 14;275(28):21396-401.
PMID 10748171
Mapping the functional domains of HAP95, a protein that binds RNA helicase A and activates the constitutive transport element of type D retroviruses.
Yang JP, Tang H, Reddy TR, Wong-Staal F.
J Biol Chem. 2001 Aug 17;276(33):30694-700. Epub 2001 Jun 11.
PMID 11402034
Nuclear DNA helicase II/RNA helicase A binds to filamentous actin.
Zhang S, Buder K, Burkhardt C, Schlott B, Gorlach M, Grosse F.
J Biol Chem. 2002 Jan 4;277(1):843-53. Epub 2001 Oct 30.
PMID 11687588
Multiple functions of nuclear DNA helicase II (RNA helicase A) in nucleic acid metabolism.
Zhang S, Grosse F.
Acta Biochim Biophys Sin (Shanghai). 2004 Mar;36(3):177-83. (REVIEW)
PMID 15202501
Nucleolar localization of murine nuclear DNA helicase II (RNA helicase A).
Zhang S, Herrmann C, Grosse F.
J Cell Sci. 1999 Aug;112 ( Pt 16):2693-703.
PMID 10413677
Nuclear DNA helicase II (RNA helicase A) binds to an F-actin containing shell that surrounds the nucleolus.
Zhang S, Kohler C, Hemmerich P, Grosse F.
Exp Cell Res. 2004 Feb 15;293(2):248-58.
PMID 14729462
DNA-dependent protein kinase (DNA-PK) phosphorylates nuclear DNA helicase II/RNA helicase A and hnRNP proteins in an RNA-dependent manner.
Zhang S, Schlott B, Gorlach M, Grosse F.
Nucleic Acids Res. 2004 Jan 2;32(1):1-10. Print 2004.
PMID 14704337
RNA helicase A in the MEF1 transcription factor complex up-regulates the MDR1 gene in multidrug-resistant cancer cells.
Zhong X, Safa AR.
J Biol Chem. 2004 Apr 23;279(17):17134-41. Epub 2004 Feb 9.
PMID 14769796
RNA helicase A interacts with dsDNA and topoisomerase IIalpha.
Zhou K, Choe KT, Zaidi Z, Wang Q, Mathews MB, Lee CG.
Nucleic Acids Res. 2003 May 1;31(9):2253-60.
PMID 12711669


This paper should be referenced as such :
Guénard F, Durocher F
DHX9 (DEAH (Asp-Glu-Ala-His) box polypeptide 9);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version :

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 4 ]
  t(1;1)(p33;q25) DHX9/TAL1
DHX9/NPL (1q25)
t(1;1)(p33;q25) DHX9/TAL1
DHX9/NPL (1q25)

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  DHX9/ZBTB37 (1q25)
t(1;5)(q25;q35) DHX9/PRELID1

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)1660
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Oct 18 17:33:45 CEST 2018

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