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INTS6 (integrator complex subunit 6)

Written2006-11Ilse Wieland
Institut für Humangenetik, Otto-von-Guericke-Universitüt, Leipziger Str. 44, 39120 Magdeburg, Germany

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DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 26
Alias_symbol (synonym)DICE1
Other aliasdeleted in cancer 1
LocusID (NCBI) 26512
Atlas_Id 40287
Location 13q14.3  [Link to chromosome band 13q14]
Location_base_pair Starts at 51361565 and ends at 51453139 bp from pter ( according to hg19-Feb_2009)  [Mapping INTS6.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
INTS6 (13q14.3) / CEP44 (4q34.1)


Description The DICE1 gene consists of 18 exons and contains a GpC-rich promoter.
Transcription A major transcript of 4.4 kb and a minor transcript of 6.9 kb was detected in fetal and adult tissues. In adult heart, brain and skeletal muscle an additional smaller transcript of 4 kb has been detected by Northern blot analysis. The DICE1 cDNA consists of 3665 bp with a coding sequence of 2661 bp; an alternatively spliced variant generated by skipping of exon 3 has been detected specifically in brain.
Pseudogene Presumably LOC285634 at 5p13.1


Description For the DICE1 protein 887 amino acids were predicted. A protein of approximately 100 kDaltons was detected by coupled in vitro transcription and translation. The Int6 protein was purified as an approximately 110 kDaltons polypeptide component of a nuclear Integrator complex.
Localisation Mainly nuclear localisation
Function Predicted motifs of DICE1 protein were a von willebrand factor a (VWFA) domain of nuclear proteins, nuclear sorting signals and a DEAD box of ATP-dependent helicases. Ectopic expression of DICE1 cDNA in tumour cells suppresses colony formation and in cell culture. The Int6 protein was purified as a subunit of a RNA polymerase II multiprotein complex with roles in transcriptional regulation and RNA processing.
Homology Weak homology to members of the helicase superfamily II


Note Mutations in the coding sequence of DICE1/DDX26 have been infrequently detected in tumour cells.
Somatic Frequent loss of heterozygosity (LOH) has been observed in lung, esophageal and prostate carcinomas. Promoter hypermethylation concomitant with reduced mRNA expression has been observed in lung and prostate carcinomas. In esophageal squamous cell carcinomas missense mutations V431I, R658Q have been detected. In prostate cancer cell line LNCaP missense mutation D546G has been described.

Implicated in

Entity Functional inactivation of the DICE1 gene has been implicated in tumorigenesis of sporadic lung carcinomas, esophagus carcinomas, prostate carcinomas and possibly other sporadic carcinomas.
Abnormal Protein A 6.3 kb fusion cDNA of a Notch-like with Dice1 cDNA (DBI-1) was detected in mouse cell line TC4. Overexpression of DBI-1 cDNA in IGF-IR transformed mouse cells compromised the mitogenic response to IGF-1 and interfered with anchorage-independent growth.
Oncogenesis Downregulation of DICE1 mRNA was detected in 7 of 8 non-small cell lung carcinoma cell lines by Northern blot analysis. Microdissected non-small cell lung carcinomas showed reduced or absent expression of DICE1 mRNA by RT-PCR. Promoter hypermethylation was found in tumour cells with downregulated DICE1 expression. Aberrantly sized transcripts were detected in two non-small cell lung carcinoma cell lines. A reduced DICE1 expression was also observed in prostate cancer cell lines DU145 and LNCaP by real-time RT-PCR. DICE1 promoter hypermethylation was detected in 6 of 10 microdissected prostate cancer samples. Ectopic expression of DICE1 cDNA inhibited colony formation of human non-small cell lung carcinoma cell lines and prostate carcinoma cell lines and suppressed anchorage-independent growth of IGF-IR transformed mouse cells.


Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II.
Baillat D, Hakimi MA, Näär AM, Shilatifard A, Cooch N, Shiekhattar R
Cell. 2005 ; 123 (2) : 265-276.
PMID 16239144
Deleted in cancer 1 (DICE1) is an essential protein controlling the topology of the inner mitochondrial membrane in C. elegans.
Han SM, Lee TH, Mun JY, Kim MJ, Kritikou EA, Lee SJ, Han SS, Hengartner MO, Koo HS
Development (Cambridge, England). 2006 ; 133 (18) : 3597-3606.
PMID 16914495
Absence of mutations in DICE1/DDX26 gene in human cancer cell lines with frequent 13q14 deletions.
Hern´ndez M, Papadopoulos N, Almeida TA
Cancer genetics and cytogenetics. 2005 ; 163 (1) : 91-92.
PMID 16271964
DBI-1, a novel gene related to the notch family, modulates mitogenic response to insulin-like growth factor 1.
Hoff HB 3rd, Tresini M, Li S, Sell C
Experimental cell research. 1998 ; 238 (2) : 359-370.
PMID 9473344
Allelic loss on chromosome 13q14 and mutation in deleted in cancer 1 gene in esophageal squamous cell carcinoma.
Li WJ, Hu N, Su H, Wang C, Goldstein AM, Wang Y, Emmert-Buck MR, Roth MJ, Guo WJ, Taylor PR
Oncogene. 2003 ; 22 (2) : 314-318.
PMID 12527901
Analysis of the mouse MAP1B gene identifies a highly conserved 4.3 kb 3' untranslated region and provides evidence against the proposed structure of DBI-1 cDNA.
Meixner A, Wiche G, Propst F
Biochimica et biophysica acta. 1999 ; 1445 (3) : 345-350.
PMID 10366719
Promoter CpG hypermethylation and downregulation of DICE1 expression in prostate cancer.
Röpke A, Buhtz P, Böhm M, Seger J, Wieland I, Allhoff EP, Wieacker PF
Oncogene. 2005 ; 24 (44) : 6667-6675.
PMID 16007164
Distribution and evolution of von Willebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere.
Whittaker CA, Hynes RO
Molecular biology of the cell. 2002 ; 13 (10) : 3369-3387.
PMID 12388743
Isolation of DICE1: a gene frequently affected by LOH and downregulated in lung carcinomas.
Wieland I, Arden KC, Michels D, Klein-Hitpass L, Böhm M, Viars CS, Weidle UH
Oncogene. 1999 ; 18 (32) : 4530-4537.
PMID 10467397
Molecular characterization of the DICE1 (DDX26) tumor suppressor gene in lung carcinoma cells.
Wieland I, Röpke A, Stumm M, Sell C, Weidle UH, Wieacker PF
Oncology research. 2001 ; 12 (11-12) : 491-500.
PMID 11939413
Ectopic expression of DICE1 suppresses tumor cell growth.
Wieland I, Sell C, Weidle UH, Wieacker P
Oncology reports. 2004 ; 12 (2) : 207-211.
PMID 15254679


This paper should be referenced as such :
Wieland, I
INTS6 (integrator complex subunit 6)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):165-166.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)INTS6   14879
Entrez_Gene (NCBI)INTS6  26512  integrator complex subunit 6
AliasesDBI-1; DDX26; DDX26A; DICE1; 
HDB; INT6; Notchl2
GeneCards (Weizmann)INTS6
Ensembl hg19 (Hinxton)ENSG00000102786 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000102786 [Gene_View]  ENSG00000102786 [Sequence]  chr13:51361565-51453139 [Contig_View]  INTS6 [Vega]
ICGC DataPortalENSG00000102786
TCGA cBioPortalINTS6
Genatlas (Paris)INTS6
SOURCE (Princeton)INTS6
Genetics Home Reference (NIH)INTS6
Genomic and cartography
GoldenPath hg38 (UCSC)INTS6  -     chr13:51361565-51453139 -  13q14.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)INTS6  -     13q14.3   [Description]    (hg19-Feb_2009)
GoldenPathINTS6 - 13q14.3 [CytoView hg19]  INTS6 - 13q14.3 [CytoView hg38]
Mapping of homologs : NCBIINTS6 [Mapview hg19]  INTS6 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AA251444 AA262171 AF086440 AF097645 AF141326
RefSeq transcript (Entrez)NM_001039937 NM_001039938 NM_001306091 NM_012141
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)INTS6
Cluster EST : UnigeneHs.439440 [ NCBI ]
CGAP (NCI)Hs.439440
Alternative Splicing GalleryENSG00000102786
Gene ExpressionINTS6 [ NCBI-GEO ]   INTS6 [ EBI - ARRAY_EXPRESS ]   INTS6 [ SEEK ]   INTS6 [ MEM ]
Gene Expression Viewer (FireBrowse)INTS6 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)26512
GTEX Portal (Tissue expression)INTS6
Human Protein AtlasENSG00000102786-INTS6 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UL03   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UL03  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UL03
Splice isoforms : SwissVarQ9UL03
Domaine pattern : Prosite (Expaxy)VWFA (PS50234)   
Domains : Interpro (EBI)INT_SG_DDX_CT_C    VWF_A    vWFA_dom_sf   
Domain families : Pfam (Sanger)INT_SG_DDX_CT_C (PF15300)    VWA_2 (PF13519)   
Domain families : Pfam (NCBI)pfam15300    pfam13519   
Conserved Domain (NCBI)INTS6
DMDM Disease mutations26512
Blocks (Seattle)INTS6
Human Protein Atlas [tissue]ENSG00000102786-INTS6 [tissue]
Peptide AtlasQ9UL03
IPIIPI00015922   IPI00738767   IPI00741295   IPI00908468   IPI00947494   IPI00947140   IPI00946585   IPI00947308   IPI00946446   IPI00946280   IPI00947301   IPI00946783   IPI00946979   
Protein Interaction databases
IntAct (EBI)Q9UL03
Ontologies - Pathways
Ontology : AmiGOtransmembrane signaling receptor activity  protein binding  nucleus  nucleoplasm  nucleoplasm  actin cytoskeleton  snRNA processing  integrator complex  integrator complex  snRNA 3'-end processing  snRNA transcription by RNA polymerase II  
Ontology : EGO-EBItransmembrane signaling receptor activity  protein binding  nucleus  nucleoplasm  nucleoplasm  actin cytoskeleton  snRNA processing  integrator complex  integrator complex  snRNA 3'-end processing  snRNA transcription by RNA polymerase II  
REACTOMEQ9UL03 [protein]
REACTOME PathwaysR-HSA-6807505 [pathway]   
NDEx NetworkINTS6
Atlas of Cancer Signalling NetworkINTS6
Wikipedia pathwaysINTS6
Orthology - Evolution
GeneTree (enSembl)ENSG00000102786
Phylogenetic Trees/Animal Genes : TreeFamINTS6
Homologs : HomoloGeneINTS6
Homology/Alignments : Family Browser (UCSC)INTS6
Gene fusions - Rearrangements
Fusion : FusionGDB17600    17601    17602    17603   
Fusion : Fusion_HubINTS6--ADAM17    INTS6--CEP44    INTS6--CUL4A    INTS6--OIP5-AS1    INTS6--SMIM14    INTS6--SSH2    PGAM5--INTS6    TSC22D1--INTS6   
Fusion : QuiverINTS6
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerINTS6 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)INTS6
Exome Variant ServerINTS6
ExAC (Exome Aggregation Consortium)ENSG00000102786
GNOMAD BrowserENSG00000102786
Varsome BrowserINTS6
Genetic variants : HAPMAP26512
Genomic Variants (DGV)INTS6 [DGVbeta]
DECIPHERINTS6 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisINTS6 
ICGC Data PortalINTS6 
TCGA Data PortalINTS6 
Broad Tumor PortalINTS6
OASIS PortalINTS6 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICINTS6  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DINTS6
Mutations and Diseases : HGMDINTS6
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch INTS6
DgiDB (Drug Gene Interaction Database)INTS6
DoCM (Curated mutations)INTS6 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)INTS6 (select a term)
NCG5 (London)INTS6
Cancer3DINTS6(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry INTS6
NextProtQ9UL03 [Medical]
Target ValidationINTS6
Huge Navigator INTS6 [HugePedia]
snp3D : Map Gene to Disease26512
BioCentury BCIQINTS6
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD26512
Chemical/Pharm GKB GenePA27212
Clinical trialINTS6
canSAR (ICR)INTS6 (select the gene name)
DataMed IndexINTS6
PubMed40 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Nov 13 21:30:39 CET 2019

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