Details for: DDX11

Gene ID: 1663

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: DDX11

Ensembl ID: ENSG00000013573

Description: DEAD/H-box helicase 11

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 5.43
    rCSI 13.19%
    PRS 91.98
  • secretory cell CL0000151
    CSI 4.27
    rCSI 4.45%
    PRS 97.41
  • ionocyte CL0005006
    CSI 3.76
    rCSI 4.03%
    PRS 98.2
  • neural crest cell CL0011012
    CSI 3.51
    rCSI 2.78%
    PRS 96.01
  • granulocyte monocyte progenitor cell CL0000557
    CSI 3.46
    rCSI 3%
    PRS 98.61
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.25
    rCSI 2.27%
    PRS 98.85
  • group 3 innate lymphoid cell CL0001071
    CSI 2.97
    rCSI 2.23%
    PRS 98.55
  • pulmonary ionocyte CL0017000
    CSI 2.92
    rCSI 3.56%
    PRS 98.53
  • common myeloid progenitor CL0000049
    CSI 2.86
    rCSI 2.31%
    PRS 98.67
  • promyelocyte CL0000836
    CSI 2.67
    rCSI 3.85%
    PRS 98.14
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.64
    rCSI 3.29%
    PRS 92.02
  • transit amplifying cell of colon CL0009011
    CSI 2.55
    rCSI 2.99%
    PRS 98.08
  • stem cell CL0000034
    CSI 2.48
    rCSI 2.39%
    PRS 96.84
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.46
    rCSI 2.85%
    PRS 94.58
  • mesenchymal cell CL0008019
    CSI 2.16
    rCSI 5.5%
    PRS 96.71
  • common dendritic progenitor CL0001029
    CSI 2.13
    rCSI 2.68%
    PRS 99.2
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.12
    rCSI 3.74%
    PRS 93.23

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [DDX11](/details-gene/1663) (DEAD/H-box helicase 11), also known as ChlR1, is an ATP-dependent DNA helicase belonging to the XPD family of helicases. It plays a fundamental role in maintaining genomic stability through its involvement in DNA repair, replication fork processing, and, most notably, the establishment and maintenance of sister chromatid cohesion during cell division ([Link](https://doi.org/10.1242/jcs.03262)). Mutations in [DDX11](/details-gene/1663) are the cause of Warsaw breakage syndrome ([OMIM [601150](https://omim.org/entry/601150)]), a rare cohesinopathy characterized by severe growth retardation and chromosomal instability ([Link](https://doi.org/10.1016/j.ajhg.2010.01.008)). Expression data indicates that **Overall**, [DDX11](/details-gene/1663) shows high significance in a diverse range of highly proliferative and metabolically active cell types, including neuronal cells, hematopoietic progenitors, and various stem and secretory cells, highlighting its essential function in cellular proliferation and maintenance. ## Cellular Roles and Expression Landscape The expression profile of [DDX11](/details-gene/1663) underscores its critical role in fundamental cellular processes rather than defining a specific cell lineage. **Overall**, its significance is highest in functionally diverse cell types that share a common requirement for high-fidelity DNA replication and cell division. Key expression patterns include: * **Nervous System:** [DDX11](/details-gene/1663) shows the highest significance in [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040) (CSI: 5.43) and is also significant in [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) and developing [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338). This suggests a vital role in both the development and potential maintenance of the neuronal genome. * **Progenitor and Stem Cells:** The gene is highly significant in multiple progenitor populations, including [granulocyte monocyte progenitor cell](/details-cell/CL0000557), [common myeloid progenitor](/details-cell/CL0000049), and [promyelocyte](/details-cell/CL0000836), as well as in undifferentiated [stem cell](/details-cell/CL0000034) populations. This is consistent with its established function in chromosome cohesion, a process essential for the rapid and accurate proliferation of these cells. * **Specialized and Secretory Cells:** High significance is also observed in [secretory cell](/details-cell/CL0000151), [ionocyte](/details-cell/CL0005006), and [pulmonary ionocyte](/details-cell/CL0017000). The functional demands on these cells, including high transcriptional activity and metabolic stress, may necessitate robust DNA repair and stress response mechanisms in which [DDX11](/details-gene/1663) is involved. The broad expression across neuronal, hematopoietic, and epithelial progenitor lineages suggests that [DDX11](/details-gene/1663) is a core component of the cellular machinery responsible for maintaining genomic integrity in actively dividing and long-lived cells. ## Pathways and Molecular Function [DDX11](/details-gene/1663) is a multifunctional helicase with well-defined biochemical activities. Its primary molecular functions include [ATP binding](/details-gene/GO:0005524), [ATP-dependent activity, acting on dna](/details-gene/GO:0008094), and [5'-3' dna helicase activity](/details-gene/GO:0043139), enabling it to unwind DNA structures ([Link](https://doi.org/10.1093/nar/28.4.917)). It also exhibits binding affinity for various DNA conformations, including [g-quadruplex dna binding](/details-gene/GO:0051880) and [dna replication origin binding](/details-gene/GO:0003688). These molecular activities are integral to several critical biological processes: * **Sister Chromatid Cohesion:** [DDX11](/details-gene/1663) is essential for the [establishment of sister chromatid cohesion](/details-gene/GO:0034085) and interacts with the Ctf18 RFC-like complex, a key player in this process ([Link](https://doi.org/10.1074/jbc.m802696200)). Its role is indispensable for proper chromosome segregation during mitosis. * **DNA Damage Response and Repair:** The gene is centrally involved in the [dna damage response](/details-gene/GO:0006974) and [dna repair](/details-gene/GO:0006281). It contributes to [replication fork processing](/details-gene/GO:0031297) and is implicated in recovery from DNA damage induced by agents like bleomycin ([GO:1904976](/details-gene/GO:1904976)) and cisplatin ([GO:0072719](/details-gene/GO:0072719)), as shown in studies on its role in replication recovery ([Link](https://doi.org/10.1016/j.yexcr.2013.06.005)). * **Cellular Stress Response:** Reactome pathway analysis links [DDX11](/details-gene/1663) to the [unfolded protein response (upr)](/details-pathway/R-HSA-381119), a component of the broader [cellular responses to stress](/details-pathway/R-HSA-2262752). This connection may explain its importance in highly active [secretory cell](/details-cell/CL0000151) types that experience high levels of endoplasmic reticulum stress. Functionally, [DDX11](/details-gene/1663) is localized to the [nucleus](/details-gene/GO:0005634), specifically within the [nucleoplasm](/details-gene/GO:0005654), [nucleolus](/details-gene/GO:0005730), and on [chromatin](/details-gene/GO:0000785), placing it at the site of its core functions. ## Research Directions The widespread importance of [DDX11](/details-gene/1663) in genome maintenance, particularly in proliferative cells, presents several avenues for future research, including its specific roles in tissue homeostasis and disease. Based on the available data, the following hypotheses can be proposed: 1. Given its critical role in sister chromatid cohesion and high significance in [granulocyte monocyte progenitor cell](/details-cell/CL0000557) and [common myeloid progenitor](/details-cell/CL0000049), depletion or dysfunction of [DDX11](/details-gene/1663) may lead to hematopoietic stem cell exhaustion or promote leukemogenesis by inducing chromosomal instability in these rapidly dividing progenitor populations. 2. The high significance of [DDX11](/details-gene/1663) in long-lived, post-mitotic cells like [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040) suggests a non-canonical, proliferation-independent role. We hypothesize that [DDX11](/details-gene/1663) is crucial for neuronal health by resolving transcription-associated R-loops or G-quadruplex structures that accumulate over time and contribute to age-related neurodegeneration. A key experiment to test the first hypothesis would involve the conditional knockout of [DDX11](/details-gene/1663) in a murine hematopoietic stem cell (HSC) model. The impact on hematopoiesis could be assessed through serial bone marrow transplantation assays to measure HSC self-renewal capacity, flow cytometry to analyze lineage differentiation, and cytogenetic analysis to quantify the accumulation of chromosomal aberrations in progenitor populations over time. **Therapeutic Potential:** [DDX11](/details-gene/1663) represents a compelling therapeutic target, particularly in oncology. Its role in DNA repair and replication makes cancer cells, which often have high replicative stress and compromised DNA damage responses, potentially more dependent on its function for survival. This is supported by evidence that [DDX11](/details-gene/1663) is essential for the survival of advanced melanomas ([Link](https://doi.org/10.1186/1476-4598-11-82)). Therefore, **inhibition** of its helicase activity with a small molecule inhibitor is a plausible therapeutic strategy. However, its importance in healthy progenitor and stem cells presents a significant risk of on-target toxicity, such as myelosuppression. A successful therapeutic approach would likely require a favorable therapeutic window or a targeted delivery system to concentrate the inhibitor in tumor tissue.

Genular Protein ID: 970077289

Symbol: DDX11_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q96FC9 Q13333 Q86VQ4 Q86W62 Q92498 Q92770 Q92998 Q92999

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 2 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CORUM 1 CPTC 1 CTD 1 ChEBI 12 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 6 Ensembl 5 ExpressionAtlas 1 GO 43 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 Pumba 1 RNAct 1 Reactome 1 RefSeq 5 Rhea 1 SMART 2 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8798685

Title: The human homologue of the yeast CHL1 gene is a novel keratinocyte growth factor regulated gene.

PubMed ID: 8798685

DOI: 10.1074/jbc.271.40.24337

PubMed ID: 9013641

Title: Characterization of putative human homologues of the yeast chromosome transmission fidelity gene, CHL1.

PubMed ID: 9013641

DOI: 10.1074/jbc.272.6.3823

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10648783

Title: Characterization of the enzymatic activity of hChlR1, a novel human DNA helicase.

PubMed ID: 10648783

DOI: 10.1093/nar/28.4.917

PubMed ID: 17105772

Title: The DNA helicase ChlR1 is required for sister chromatid cohesion in mammalian cells.

PubMed ID: 17105772

DOI: 10.1242/jcs.03262

PubMed ID: 17189189

Title: ChlR1 is required for loading papillomavirus E2 onto mitotic chromosomes and viral genome maintenance.

PubMed ID: 17189189

DOI: 10.1016/j.molcel.2006.11.005

PubMed ID: 18499658

Title: Studies with the human cohesin establishment factor, ChlR1. Association of ChlR1 with Ctf18-RFC and Fen1.

PubMed ID: 18499658

DOI: 10.1074/jbc.m802696200

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 20137776

Title: Warsaw breakage syndrome, a cohesinopathy associated with mutations in the XPD helicase family member DDX11/ChlR1.

PubMed ID: 20137776

DOI: 10.1016/j.ajhg.2010.01.008

PubMed ID: 20124417

Title: Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion.

PubMed ID: 20124417

DOI: 10.1242/jcs.057984

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21854770

Title: Mammalian ChlR1 has a role in heterochromatin organization.

PubMed ID: 21854770

DOI: 10.1016/j.yexcr.2011.08.006

PubMed ID: 22102414

Title: Biochemical characterization of Warsaw breakage syndrome helicase.

PubMed ID: 22102414

DOI: 10.1074/jbc.m111.276022

PubMed ID: 23116066

Title: The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced melanomas.

PubMed ID: 23116066

DOI: 10.1186/1476-4598-11-82

PubMed ID: 23797032

Title: Roles of ChlR1 DNA helicase in replication recovery from DNA damage.

PubMed ID: 23797032

DOI: 10.1016/j.yexcr.2013.06.005

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 26089203

Title: The Warsaw breakage syndrome-related protein DDX11 is required for ribosomal RNA synthesis and embryonic development.

PubMed ID: 26089203

DOI: 10.1093/hmg/ddv213

PubMed ID: 27477908

Title: A Long Noncoding RNA Regulates Sister Chromatid Cohesion.

PubMed ID: 27477908

DOI: 10.1016/j.molcel.2016.06.031

PubMed ID: 26503245

Title: Tim/Timeless, a member of the replication fork protection complex, operates with the Warsaw breakage syndrome DNA helicase DDX11 in the same fork recovery pathway.

PubMed ID: 26503245

DOI: 10.1093/nar/gkv1112

PubMed ID: 32705708

Title: Timeless couples G-quadruplex detection with processing by DDX11 helicase during DNA replication.

PubMed ID: 32705708

DOI: 10.15252/embj.2019104185

PubMed ID: 23033317

Title: Identification and biochemical characterization of a novel mutation in DDX11 causing warsaw breakage syndrome.

PubMed ID: 23033317

DOI: 10.1002/humu.22226

Sequence Information:

  • Length: 970
  • Mass: 108313
  • Checksum: 5BF49FE74E912B48
  • Sequence:
    • MANETQKVGA IHFPFPFTPY SIQEDFMAEL YRVLEAGKIG IFESPTGTGK SLSLICGALS 
WLRDFEQKKR EEEARLLETG TGPLHDEKDE SLCLSSSCEG AAGTPRPAGE PAWVTQFVQK 
KEERDLVDRL KAEQARRKQR EERLQQLQHR VQLKYAAKRL RQEEEERENL LRLSREMLET 
GPEAERLEQL ESGEEELVLA EYESDEEKKV ASRVDEDEDD LEEEHITKIY YCSRTHSQLA 
QFVHEVKKSP FGKDVRLVSL GSRQNLCVNE DVKSLGSVQL INDRCVDMQR SRHEKKKGAE 
EEKPKRRRQE KQAACPFYNH EQMGLLRDEA LAEVKDMEQL LALGKEARAC PYYGSRLAIP 
AAQLVVLPYQ MLLHAATRQA AGIRLQDQVV IIDEAHNLID TITGMHSVEV SGSQLCQAHS 
QLLQYVERYG KRLKAKNLMY LKQILYLLEK FVAVLGGNIK QNPNTQSLSQ TGTELKTIND 
FLFQSQIDNI NLFKVQRYCE KSMISRKLFG FTERYGAVFS SREQPKLAGF QQFLQSLQPR 
TTEALAAPAD ESQASTLRPA SPLMHIQGFL AALTTANQDG RVILSRQGSL SQSTLKFLLL 
NPAVHFAQVV KECRAVVIAG GTMQPVSDFR QQLLACAGVE AERVVEFSCG HVIPPDNILP 
LVICSGISNQ PLEFTFQKRE LPQMMDEVGR ILCNLCGVVP GGVVCFFPSY EYLRQVHAHW 
EKGGLLGRLA ARKKIFQEPK SAHQVEQVLL AYSRCIQACG QERGQVTGAL LLSVVGGKMS 
EGINFSDNLG RCVVMVGMPF PNIRSAELQE KMAYLDQTLS PRPGTPREGS GGEPVHEGRQ 
PVHRQGHQAP EGFCQRSAPG PAICPAPCPG QAAGLDPSPC GGQSYLWPRH CCCAEVSPGE 
VGLFLMGNHT TAWRRALPLS CPLETVFVVG VVCGDPVTKV KPRRRVWSPE CCQDPGTGVS 
SRRRKWGNPE

Genular Protein ID: 3463577510

Symbol: Q2NKM7_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q2NKM7

Database IDs:

ARBA 11 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 1 DNASU 1 DisGeNET 1 EMBL 2 GO 7 Gene3D 1 InterPro 7 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 3 SAM 2 SMART 2 SUPFAM 1 iPTMnet 1

Citations:

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 906
  • Mass: 101622
  • Checksum: 2C4916339682C62B
  • Sequence:
    • MANETQKVGA IHFPFPFTPY SIQEDFMAEL YRVLEAGKIG IFESPTGTGK SLSLICGALS 
WLRDFEQKKR EEEARLLETG TGPLHDEKDE SLCLSSSCEG AAGTPRPAGE PAWVTQFVQK 
KEERDLVDRL KAEQARRKQR EERLQQLQHR VQLKYAAKRL RQEEEERENL LRLSREMLET 
GPEAERLEQL ESGEEELVLA EYESDEEKKV ASRVDEDEDD LEEEHITKIY YCSRTHSQLA 
QFVHEVKKSP FGKDVRLVSL GSRQNLCVNE DVKSLGSVQL INDRCVDMQR SRHEKKKGAE 
EEKPKRRRQE KQAACPFYNH EQMGLLRDEA LAEVKDMEQL LALGKEARAC PYYGSRLAIP 
AAQLVVLPYQ MLLHAATRQA AGIRLQDQVV IIDEAHNLID TITGMHSVEV SGSQLCQAHS 
QLLQYVERYG KRLKAKNLMY LKQILYLLEK FVAVLGGNIK QNPNTQSLSQ TGTELKTIND 
FLFQSQIDNI NLFKVQRYCE KSMISRKLFG FTERYGAVFS SREQPKLAGF QQFLQSLQPR 
TTEALAAPAD ESQASVPQPA SPLMHIEGFL AALTTANQDG RVILSRQGSL SQSTLKFLLL 
NPAVHFAQVV KECRAVVIAG GTMQPVSDFR QQLLACAGVE AERVVEFSCG HVIPPDNILP 
LVICIGVSNQ PLEFTFQKRD LPQMMDEVGR ILCNLCSVVS GGVVCFFPSY EYLRQVHAHW 
EKGGLLGHLA ARKKIFQEPK SAHQVEQVLL AYSRCIQACG QERGPVTGAL LLSVVGGKMS 
EGINFSDNLG RCVVMVGMPF PNIRSAELQE KMAYLDQTLP RAPGQAPPGK ALVENLCMKA 
VNQSIGRAIR HQKDFASIVL LDQRYARPPV LAKLPAWIRA RVEVKATFGP AIAAVQKFHR 
EKSASS