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CDC6 (cell division cycle 6 homolog (S. cerevisiae))

Written2008-01Michael Zachariadis, Vassilis G Gorgoulis
University of Athens, Faculty of Medicine, Department of Anatomy (MZ) ; Department of Histology, Embryology, Molecular Carcinogenesis Group (VGG)

(Note : for Links provided by Atlas : click)

Identity

Alias_namesCDC18L
CDC6 (cell division cycle 6, S. cerevisiae) homolog
CDC6 cell division cycle 6 homolog (S. cerevisiae)
cell division cycle 6 homolog (S. cerevisiae)
Other aliascdc6
hCDC6
HsCDC18
HsCDC6
p62
HGNC (Hugo) CDC6
LocusID (NCBI) 990
Atlas_Id 40014
Location 17q21.2  [Link to chromosome band 17q21]
Location_base_pair Starts at 40287894 and ends at 40303161 bp from pter ( according to hg19-Feb_2009)  [Mapping CDC6.png]
Local_order centrosome ---- CASC3-RAPGEFL1-WIPF2-CDC6-RARA-TOP2A
Fusion genes
(updated 2017)		Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CACNB1 (17q12) / CDC6 (17q21.2)CDC6 (17q21.2) / CDC6 (17q21.2)CDC6 (17q21.2) / GK5 (3q23)
CDC6 (17q21.2) / IKZF3 (17q12)CDC6 (17q21.2) / RAPGEFL1 (17q21.1)CDC6 (17q21.2) / RNFT1 (17q23.1)
PTBP3 (9q32) / CDC6 (17q21.2)RARA (17q21.2) / CDC6 (17q21.2)UTP6 (17q11.2) / CDC6 (17q21.2)

DNA/RNA

Description The gene starts at 35697672 bp from pter and ends at 35712939 bp from pter. Its size is 15267 bases and its orientation lie at the plus strand.
The 5' promoter region contains putative sites for transcriptional control, including an initiator element, a CHR element, two main binding sites for E2F, a putative Sp1 site, and a CCAAT region. No consensus TATA box is evident. This resembles the organization of other genes encoding proteins associated with the G1/S transition.
Transcription The gene has 12 exons. The five putative transcripts (see table below) encode the same product of 560aa. There are about 230 EST sequences.
Accession N°
Transcript length (bp)
Notes
NM_001254
3053
RefSeq
CR598029
1802
mRNA
BC025232
2861
mRNA
HSU77949
2653
mRNA
AF022109
2021
mRNA
Pseudogene there are no known pseudogenes

Protein

Description The CDC6 protein or p62 is composed of 560 amino acids with a molecular weight of 62720 Da. The central portion of the protein contains a conserved nucleotide binding/ATPase domain, which classifies it to a large superfamily of ATPases known as "ATPases associated with various cellular activities" (AAA) proteins and specifically to the AAA+ subfamily. The Walker-A motif GXXGXGK(T/S) (nucleotide binding) of the AAA+ domain spans aa 202-209, while the Walker-B motif D(D/E)XX (nucleotide hydrolysis) spans aa 284-287. The domain contains also a leucine zipper (aa 306-327), and a caspase dependent cleavage site DQL290DS.
The N-terminal domain contains: three consensus phosphorylation sites at serine (S)54, S74 and S106, which are phosphorylated in vivo by CDK-related activity at the G1/S boundary; a putative conserved nuclear localization sequence ((S/T)PXK57R58(L/I)); two putative destruction boxes (D-box (aa 56-64) and KEN box (aa 81-83)), which target CDC6 for proteolysis by APCCDH1 during early G1 or G0, but not S, G2 or M; and a cyclin binding domain mapped to a Cy-motif (aa 93-100) that is similar to the cyclin binding regions in p21/WAF1/SDI1 and E2F-1.
The C-terminal domain contains: a putative classical nuclear export signal (NES) between residues 462-488 (ILVCSLMLLIRQLKI), a caspase dependent cleavage site SEV442DG, and a conserved winged-helix domain (WHD) with unknown function; it possibly mediates protein-protein interactions or a direct interaction with the DNA helix.
Expression It is expressed in all proliferating cells but not in quiescent or differentiated cells.
Localisation Even though it was believed at first that p62CDC6 was nuclear during G1 and cytoplasmic during S and G2, lately it has been found that there is an endogenous fraction of the protein that remains chromatin-bound throughout the cell cycle.
Function - ATP binding
- Chromatin binding
- Nucleoside-triphosphatase activity
- Nucleotide binding
- Protein binding
- Loading factor for MCM2-7: Cdc6/Cdc18 is recruited to replication origins by ORC. Once localized at replication origins, Cdc6 helps to recruit and load MCM factors onto DNA in a process that requires CDC6-mediated ATP hydrolysis. After loading of MCM2-7 on DNA, CDC6 is not necessary for origin firing and dissociates from the complex, through a phosphorylation-dependent procedure. It seems though that CDC6 has additional roles related to S/M checkpoint control. Accumulating evidence suggests that CDC6 is required for proper control of mitotic entry. Deregulation of CDC6 results in mitotic block, aberrant mitotic progression, or apoptosis.
Homology ORC1

Mutations

Note No known mutations

Implicated in

Note
  
Entity Carcinogenesis
Note Because of its key role in DNA replication, deregulation of CDC6 could lead to genomic instability fueling the risk for neoplastic transformation. Indeed, CDC6 upregulation has been observed in many cancerous lesions, including brain tumors, non-small cell lung carcinomas, mantle cell lymphomas, and various cervical neoplasias. Interestingly, in aggressive prostate cancer, CDC6 is downregulated.
CDC6 encompasses certain oncogenic characteristics that manifest themselves when CDC6 expression is deregulated. For example, CDC6 induces DNA replication in quiescent cells, while in certain occasions overexpression of CDC6 leads to DNA overreplication in tumour cells.
While cells have mechanisms to prevent aberrant DNA replication, deregulation of CDC6, or /and its partner in pre-RCs, CDT1 may lead to abrogation of the antitumor barriers of senescence and apoptosis. In addition their stable expression in premalignant papilloma cells lead to transformation of these cells, which upon injection into nude mice produce tumors, an activity that clearly portrays the oncogenic potential of CDC6 deregulation.
Moreover, deregulation of CDC6 may lead to inactivation of the INK4/ARF locus through recruitment of histone deacetylases HDAC1 and HDAC2 and heterochromatinization of the INK4/ARF locus. This locus encodes the tumour suppressor genes p16INK4a, p15INK4b, and ARF, and inactivation of this locus is closely related to cancer.
  

Bibliography

CDKs give Cdc6 a license to drive into S phase.
Ayad NG
Cell. 2005 ; 122 (6) : 825-827.
PMID 16179249
 
Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints.
Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, Vassiliou LV, Kolettas E, Niforou K, Zoumpourlis VC, Takaoka M, Nakagawa H, Tort F, Fugger K, Johansson F, Sehested M, Andersen CL, Dyrskjot L, Ørntoft T, Lukas J, Kittas C, Helleday T, Halazonetis TD, Bartek J, Gorgoulis VG
Nature. 2006 ; 444 (7119) : 633-637.
PMID 17136093
 
Synthesis and turn-over of the replicative Cdc6 protein during the HeLa cell cycle.
Biermann E, Baack M, Kreitz S, Knippers R
European journal of biochemistry / FEBS. 2002 ; 269 (3) : 1040-1046.
PMID 11846807
 
Targeted destruction of DNA replication protein Cdc6 by cell death pathways in mammals and yeast.
Blanchard F, Rusiniak ME, Sharma K, Sun X, Todorov I, Castellano MM, Gutierrez C, Baumann H, Burhans WC
Molecular biology of the cell. 2002 ; 13 (5) : 1536-1549.
PMID 12006651
 
Immunohistochemical localization of cdc6 in squamous and glandular neoplasia of the uterine cervix.
Bonds L, Baker P, Gup C, Shroyer KR
Archives of pathology & laboratory medicine. 2002 ; 126 (10) : 1164-1168.
PMID 12296751
 
CDC6: from DNA replication to cell cycle checkpoints and oncogenesis.
Borlado LR, Méndez J
Carcinogenesis. 2008 ; 29 (2) : 237-243.
PMID 18048387
 
Human replication protein Cdc6 prevents mitosis through a checkpoint mechanism that implicates Chk1.
Clay-Farrace L, Pelizon C, Santamaria D, Pines J, Laskey RA
The EMBO journal. 2003 ; 22 (3) : 704-712.
PMID 12554670
 
The regulated association of Cdt1 with minichromosome maintenance proteins and Cdc6 in mammalian cells.
Cook JG, Chasse DA, Nevins JR
The Journal of biological chemistry. 2004 ; 279 (10) : 9625-9633.
PMID 14672932
 
Analysis of Cdc6 function in the assembly of mammalian prereplication complexes.
Cook JG, Park CH, Burke TW, Leone G, DeGregori J, Engel A, Nevins JR
Proceedings of the National Academy of Sciences of the United States of America. 2002 ; 99 (3) : 1347-1352.
PMID 11805305
 
Chromatin-bound Cdc6 persists in S and G2 phases in human cells, while soluble Cdc6 is destroyed in a cyclin A-cdk2 dependent process.
Coverley D, Pelizon C, Trewick S, Laskey RA
Journal of cell science. 2000 ; 113 ( Pt 11) : 1929-1938.
PMID 10806104
 
Multiple mechanisms regulate subcellular localization of human CDC6.
Delmolino LM, Saha P, Dutta A
The Journal of biological chemistry. 2001 ; 276 (29) : 26947-26954.
PMID 11346650
 
p53-Dependent regulation of Cdc6 protein stability controls cellular proliferation.
Duursma A, Agami R
Molecular and cellular biology. 2005 ; 25 (16) : 6937-6947.
PMID 16055707
 
Nuclear organization of DNA replication initiation proteins in mammalian cells.
Fujita M, Ishimi Y, Nakamura H, Kiyono T, Tsurumi T
The Journal of biological chemistry. 2002 ; 277 (12) : 10354-10361.
PMID 11779870
 
Cell cycle regulation of human CDC6 protein. Intracellular localization, interaction with the human mcm complex, and CDC2 kinase-mediated hyperphosphorylation.
Fujita M, Yamada C, Goto H, Yokoyama N, Kuzushima K, Inagaki M, Tsurumi T
The Journal of biological chemistry. 1999 ; 274 (36) : 25927-25932.
PMID 10464337
 
Oncogenic activity of Cdc6 through repression of the INK4/ARF locus.
Gonzalez S, Klatt P, Delgado S, Conde E, Lopez-Rios F, Sanchez-Cespedes M, Mendez J, Antequera F, Serrano M
Nature. 2006 ; 440 (7084) : 702-706.
PMID 16572177
 
Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA damage.
Hall JR, Kow E, Nevis KR, Lu CK, Luce KS, Zhong Q, Cook JG
Molecular biology of the cell. 2007 ; 18 (9) : 3340-3350.
PMID 17567951
 
Cell cycle-regulated expression of mammalian CDC6 is dependent on E2F.
Hateboer G, Wobst A, Petersen BO, Le Cam L, Vigo E, Sardet C, Helin K
Molecular and cellular biology. 1998 ; 18 (11) : 6679-6697.
PMID 9774682
 
Mutation of cyclin/cdk phosphorylation sites in HsCdc6 disrupts a late step in initiation of DNA replication in human cells.
Herbig U, Griffith JW, Fanning E
Molecular biology of the cell. 2000 ; 11 (12) : 4117-4130.
PMID 11102512
 
The Cdc6 nucleotide-binding site regulates its activity in DNA replication in human cells.
Herbig U, Marlar CA, Fanning E
Molecular biology of the cell. 1999 ; 10 (8) : 2631-2645.
PMID 10436018
 
Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6.
Jiang W, Wells NJ, Hunter T
Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (11) : 6193-6198.
PMID 10339564
 
Overexpression of the replication licensing regulators hCdt1 and hCdc6 characterizes a subset of non-small-cell lung carcinomas: synergistic effect with mutant p53 on tumor growth and chromosomal instability--evidence of E2F-1 transcriptional control over hCdt1.
Karakaidos P, Taraviras S, Vassiliou LV, Zacharatos P, Kastrinakis NG, Kougiou D, Kouloukoussa M, Nishitani H, Papavassiliou AG, Lygerou Z, Gorgoulis VG
The American journal of pathology. 2004 ; 165 (4) : 1351-1365.
PMID 15466399
 
The functional role of Cdc6 in S-G2/M in mammalian cells.
Lau E, Zhu C, Abraham RT, Jiang W
EMBO reports. 2006 ; 7 (4) : 425-430.
PMID 16439999
 
Deregulated overexpression of hCdt1 and hCdc6 promotes malignant behavior.
Liontos M, Koutsami M, Sideridou M, Evangelou K, Kletsas D, Levy B, Kotsinas A, Nahum O, Zoumpourlis V, Kouloukoussa M, Lygerou Z, Taraviras S, Kittas C, Bartkova J, Papavassiliou AG, Bartek J, Halazonetis TD, Gorgoulis VG
Cancer research. 2007 ; 67 (22) : 10899-10909.
PMID 18006835
 
Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis.
Méndez J, Stillman B
Molecular and cellular biology. 2000 ; 20 (22) : 8602-8612.
PMID 11046155
 
CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis.
Mailand N, Diffley JF
Cell. 2005 ; 122 (6) : 915-926.
PMID 16153703
 
Quantitation of CDC6 and MCM5 mRNA in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix.
Murphy N, Ring M, Heffron CC, Martin CM, McGuinness E, Sheils O, O'Leary JJ
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2005 ; 18 (6) : 844-849.
PMID 15696126
 
Cdc6 expression as a marker of proliferative activity in brain tumors.
Ohta S, Koide M, Tokuyama T, Yokota N, Nishizawa S, Namba H
Oncology reports. 2001 ; 8 (5) : 1063-1066.
PMID 11496317
 
Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F.
Ohtani K, Tsujimoto A, Ikeda M, Nakamura M
Oncogene. 1998 ; 17 (14) : 1777-1785.
PMID 9778043
 
Down to the origin: Cdc6 protein and the competence to replicate.
Pelizon C
Trends in cell biology. 2003 ; 13 (3) : 110-113.
PMID 12628342
 
Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1.
Petersen BO, Wagener C, Marinoni F, Kramer ER, Melixetian M, Lazzerini Denchi E, Gieffers C, Matteucci C, Peters JM, Helin K
Genes & development. 2000 ; 14 (18) : 2330-2343.
PMID 10995389
 
Unbalanced expression of licensing DNA replication factors occurs in a subset of mantle cell lymphomas with genomic instability.
Pinyol M, Salaverria I, Bea S, Fern´ndez V, Colomo L, Campo E, Jares P
International journal of cancer. Journal international du cancer. 2006 ; 119 (12) : 2768-2774.
PMID 17036332
 
Down-regulation of Cdc6, a cell cycle regulatory gene, in prostate cancer.
Robles LD, Frost AR, Davila M, Hutson AD, Grizzle WE, Chakrabarti R
The Journal of biological chemistry. 2002 ; 277 (28) : 25431-25438.
PMID 12006585
 
Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase.
Saha P, Chen J, Thome KC, Lawlis SJ, Hou ZH, Hendricks M, Parvin JD, Dutta A
Molecular and cellular biology. 1998 ; 18 (5) : 2758-2767.
PMID 9566895
 
Recruitment of ORC or CDC6 to DNA is sufficient to create an artificial origin of replication in mammalian cells.
Takeda DY, Shibata Y, Parvin JD, Dutta A
Genes & development. 2005 ; 19 (23) : 2827-2836.
PMID 16322558
 
Identification of the sequence responsible for the nuclear localization of human Cdc6.
Takei Y, Yamamoto K, Tsujimoto G
FEBS letters. 1999 ; 447 (2-3) : 292-296.
PMID 10214964
 
A p53-dependent checkpoint pathway prevents rereplication.
Vaziri C, Saxena S, Jeon Y, Lee C, Murata K, Machida Y, Wagle N, Hwang DS, Dutta A
Molecular cell. 2003 ; 11 (4) : 997-1008.
PMID 12718885
 
A human protein related to yeast Cdc6p.
Williams RS, Shohet RV, Stillman B
Proceedings of the National Academy of Sciences of the United States of America. 1997 ; 94 (1) : 142-147.
PMID 8990175
 
Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells.
Yan Z, DeGregori J, Shohet R, Leone G, Stillman B, Nevins JR, Williams RS
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (7) : 3603-3608.
PMID 9520412
 
Cleavage of Cdc6 by caspase-3 promotes ATM/ATR kinase-mediated apoptosis of HeLa cells.
Yim H, Hwang IS, Choi JS, Chun KH, Jin YH, Ham YM, Lee KY, Lee SK
The Journal of cell biology. 2006 ; 174 (1) : 77-88.
PMID 16801388
 

Citation

This paper should be referenced as such :
Zachariadis, M ; Gorgoulis, VG. CDC6 (cell division cycle 6 homolog (S
cerevisiae))
Atlas Genet Cytogenet Oncol Haematol. 2008;12(5):362-364.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CDC6ID40014ch17q21.html

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Male breast cancer

External links

Nomenclature
HGNC (Hugo)CDC6   1744
Cards
AtlasCDC6ID40014ch17q21
Entrez_Gene (NCBI)CDC6  990  cell division cycle 6
AliasesCDC18L; HsCDC18; HsCDC6; MGORS5
GeneCards (Weizmann)CDC6
Ensembl hg19 (Hinxton)ENSG00000094804 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000094804 [Gene_View]  chr17:40287894-40303161 [Contig_View]  CDC6 [Vega]
ICGC DataPortalENSG00000094804
TCGA cBioPortalCDC6
AceView (NCBI)CDC6
Genatlas (Paris)CDC6
WikiGenes990
SOURCE (Princeton)CDC6
Genetics Home Reference (NIH)CDC6
Genomic and cartography
GoldenPath hg38 (UCSC)CDC6  -     chr17:40287894-40303161 +  17q21.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CDC6  -     17q21.2   [Description]    (hg19-Feb_2009)
EnsemblCDC6 - 17q21.2 [CytoView hg19]  CDC6 - 17q21.2 [CytoView hg38]
Mapping of homologs : NCBICDC6 [Mapview hg19]  CDC6 [Mapview hg38]
OMIM602627   613805   
Gene and transcription
Genbank (Entrez)AA210818 AF022109 AK313620 BC025232 BE296640
RefSeq transcript (Entrez)NM_001254
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CDC6
Cluster EST : UnigeneHs.405958 [ NCBI ]
CGAP (NCI)Hs.405958
Alternative Splicing GalleryENSG00000094804
Gene ExpressionCDC6 [ NCBI-GEO ]   CDC6 [ EBI - ARRAY_EXPRESS ]   CDC6 [ SEEK ]   CDC6 [ MEM ]
Gene Expression Viewer (FireBrowse)CDC6 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)990
GTEX Portal (Tissue expression)CDC6
Human Protein AtlasENSG00000094804-CDC6 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ99741   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ99741  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ99741
Splice isoforms : SwissVarQ99741
PhosPhoSitePlusQ99741
Domains : Interpro (EBI)AAA+_ATPase    Cdc6/18    Cdc6_C    P-loop_NTPase    WHTH_DNA-bd_dom   
Domain families : Pfam (Sanger)AAA_22 (PF13401)    Cdc6_C (PF09079)   
Domain families : Pfam (NCBI)pfam13401    pfam09079   
Domain families : Smart (EMBL)AAA (SM00382)  Cdc6_C (SM01074)  
Conserved Domain (NCBI)CDC6
DMDM Disease mutations990
Blocks (Seattle)CDC6
PDB (SRS)2CCH    2CCI    4I5L    4I5N   
PDB (PDBSum)2CCH    2CCI    4I5L    4I5N   
PDB (IMB)2CCH    2CCI    4I5L    4I5N   
PDB (RSDB)2CCH    2CCI    4I5L    4I5N   
Structural Biology KnowledgeBase2CCH    2CCI    4I5L    4I5N   
SCOP (Structural Classification of Proteins)2CCH    2CCI    4I5L    4I5N   
CATH (Classification of proteins structures)2CCH    2CCI    4I5L    4I5N   
SuperfamilyQ99741
Human Protein Atlas [tissue]ENSG00000094804-CDC6 [tissue]
Peptide AtlasQ99741
HPRD04022
IPIIPI00014575   
Protein Interaction databases
DIP (DOE-UCLA)Q99741
IntAct (EBI)Q99741
FunCoupENSG00000094804
BioGRIDCDC6
STRING (EMBL)CDC6
ZODIACCDC6
Ontologies - Pathways
QuickGOQ99741
Ontology : AmiGODNA replication checkpoint  regulation of cyclin-dependent protein serine/threonine kinase activity  G1/S transition of mitotic cell cycle  regulation of transcription involved in G1/S transition of mitotic cell cycle  nucleotide binding  mitotic cell cycle  spindle pole  protein binding  ATP binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  Golgi apparatus  cytosol  cytosol  DNA replication  DNA replication initiation  traversing start control point of mitotic cell cycle  negative regulation of DNA replication  negative regulation of cell proliferation  kinase binding  regulation of mitotic metaphase/anaphase transition  positive regulation of cytokinesis  positive regulation of cyclin-dependent protein serine/threonine kinase activity  positive regulation of fibroblast proliferation  spindle midzone  cell division  positive regulation of chromosome segregation  cellular response to vasopressin  cellular response to angiotensin  
Ontology : EGO-EBIDNA replication checkpoint  regulation of cyclin-dependent protein serine/threonine kinase activity  G1/S transition of mitotic cell cycle  regulation of transcription involved in G1/S transition of mitotic cell cycle  nucleotide binding  mitotic cell cycle  spindle pole  protein binding  ATP binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  Golgi apparatus  cytosol  cytosol  DNA replication  DNA replication initiation  traversing start control point of mitotic cell cycle  negative regulation of DNA replication  negative regulation of cell proliferation  kinase binding  regulation of mitotic metaphase/anaphase transition  positive regulation of cytokinesis  positive regulation of cyclin-dependent protein serine/threonine kinase activity  positive regulation of fibroblast proliferation  spindle midzone  cell division  positive regulation of chromosome segregation  cellular response to vasopressin  cellular response to angiotensin  
Pathways : BIOCARTACDK Regulation of DNA Replication [Genes]   
Pathways : KEGGCell cycle   
REACTOMEQ99741 [protein]
REACTOME PathwaysR-HSA-69300 [pathway]   
NDEx NetworkCDC6
Atlas of Cancer Signalling NetworkCDC6
Wikipedia pathwaysCDC6
Orthology - Evolution
OrthoDB990
GeneTree (enSembl)ENSG00000094804
Phylogenetic Trees/Animal Genes : TreeFamCDC6
HOVERGENQ99741
HOGENOMQ99741
Homologs : HomoloGeneCDC6
Homology/Alignments : Family Browser (UCSC)CDC6
Gene fusions - Rearrangements
Fusion : MitelmanCACNB1/CDC6 [17q12/17q21.2]  [t(17;17)(q12;q21)]  
Fusion : MitelmanCDC6/IKZF3 [17q21.2/17q12]  [t(17;17)(q12;q21)]  
Fusion : MitelmanCDC6/RNFT1 [17q21.2/17q23.1]  [t(17;17)(q21;q23)]  
Fusion : MitelmanRARA/CDC6 [17q21.2/17q21.2]  [t(17;17)(q21;q21)]  
Fusion: TCGACACNB1 17q12 CDC6 17q21.2 BRCA
Fusion: TCGACDC6 17q21.2 RNFT1 17q23.1 BRCA
Fusion: TCGARARA 17q21.2 CDC6 17q21.2 LUAD
Fusion: TCGARP11-546D6.2 CDC6 17q21.2 LUSC
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCDC6 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CDC6
dbVarCDC6
ClinVarCDC6
1000_GenomesCDC6 
Exome Variant ServerCDC6
ExAC (Exome Aggregation Consortium)ENSG00000094804
GNOMAD BrowserENSG00000094804
Genetic variants : HAPMAP990
Genomic Variants (DGV)CDC6 [DGVbeta]
DECIPHERCDC6 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCDC6 
Mutations
ICGC Data PortalCDC6 
TCGA Data PortalCDC6 
Broad Tumor PortalCDC6
OASIS PortalCDC6 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCDC6  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCDC6
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 CDC6
DgiDB (Drug Gene Interaction Database)CDC6
DoCM (Curated mutations)CDC6 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CDC6 (select a term)
intoGenCDC6
NCG5 (London)CDC6
Cancer3DCDC6(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602627    613805   
Orphanet2357   
MedgenCDC6
Genetic Testing Registry CDC6
NextProtQ99741 [Medical]
TSGene990
GENETestsCDC6
Target ValidationCDC6
Huge Navigator CDC6 [HugePedia]
snp3D : Map Gene to Disease990
BioCentury BCIQCDC6
ClinGenCDC6
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD990
Chemical/Pharm GKB GenePA26271
Clinical trialCDC6
Miscellaneous
canSAR (ICR)CDC6 (select the gene name)
Probes
Litterature
PubMed123 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCDC6
EVEXCDC6
GoPubMedCDC6
iHOPCDC6
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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