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FANCD2 (Fanconi anemia, complementation group D2)

Written1998-04Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2002-06Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

Alias_namesFACD
FANCD
Alias_symbol (synonym)FAD
FA-D2
Other aliasFAD2
HGNC (Hugo) FANCD2
LocusID (NCBI) 2177
Atlas_Id 103
Location 3p25.3  [Link to chromosome band 3p25]
Location_base_pair Starts at 10026387 and ends at 10101937 bp from pter ( according to hg19-Feb_2009)  [Mapping FANCD2.png]
Local_order not far from XPC, in 3p25
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2016)		FANCD2 (3p25.3) / CMTM6 (3p22.3)FANCD2 (3p25.3) / MTMR14 (3p25.3)PCNX1 (14q24.2) / FANCD2 (3p25.3)
RAD18 (3p25.3) / FANCD2 (3p25.3)

DNA/RNA

Description 44 exons; 4356 bp open reading frame; the first exon is non-coding.

Protein

Description 1452 amino acids; 155 kDa (FANCD2-S isoform, for short), and 162 kDa (FANCD2-L isoform, for long) by ubiquitin addition
Expression weak
Localisation nucleus
Function the FA complex is comprised of : FANCA, FANCC, FANCE, FANCF, and FANCG; this complex is only found in the nucleus.
  • FANCA and FANCG form a complex in the cytoplasm, through a N-term FANCA (involving the nuclear localization signal) - FANCG interaction; FANCC join the complex; phosphorylation of FANCA would induce its translocation into the nucleus.This FA complex translocates into the nucleus, where FANCE and FANCF are present; FANCE and FANCF join the complex. The FA complex subsequently interacts with FANCD2 by monoubiquitination of FANCD2 during S phase or following DNA damage. Activated (ubiquinated ) FANCD2 (i.e. FANCD2-L), downstream in the FA pathway, will then interact with other proteins involved in DNA repair, possibly BRCA1; after DNA repair, FANCD2 return to the non-ubiquinated form (FANCD2-S).
  • FANCD2co-localizes with BRCA1 in DNA damaged-induced loci and in the synaptonemal complex of meotic chromosomes as well.
    • Homology significant homologies can be found with proteins from various species

    Implicated in

    Note
      
    Entity Fanconi anaemia (FA); FANCD2 is implicated in the FA complementation group D, a heterogeneous group, with at least 2 genes: FANCD2, and a yet undiscovered FANCD1. FA complementation group D represents about 1% of FA cases. In FA complementation group D patients, the FA complex is normal, in contrast with results found in group A, B (with a yet unknown gene), C, E, F, and G patients.
    Disease Fanconi anaemia is a chromosome instability syndrome/cancer prone disease (at risk of leukaemia and squamous cell carcinoma)
    Prognosis Fanconi anaemia's prognosis is poor; mean survival is 20 years: patients die of bone marrow failure (infections, haemorrhages), leukaemia, or solid cancer.
  • It has recently been shown that significant phenotypic differences were found between the various complementation groups. Patients from the rare groups FA-D, FA-E, and FA-F had somatic abnormalities more frequently.
    • Cytogenetics Spontaneously enhanced chromatid-type aberrations (breaks, gaps, interchanges; increased rate of breaks compared to control, when induced by specific clastogens known as DNA cross-linking agents (e.g. mitomycin C, diepoxybutane).
      

    Bibliography

    Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia.
    Callén E, Samper E, Ramírez MJ, Creus A, Marcos R, Ortega JJ, Olivé T, Badell I, Blasco MA, Surrallés J
    Human molecular genetics. 2002 ; 11 (4) : 439-444.
    PMID 11854176
     
    Molecular biology of Fanconi anemia: implications for diagnosis and therapy.
    D'Andrea AD, Grompe M
    Blood. 1997 ; 90 (5) : 1725-1736.
    PMID 9292505
     
    Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group.
    Faivre L, Guardiola P, Lewis C, Dokal I, Ebell W, Zatterale A, Altay C, Poole J, Stones D, Kwee ML, van Weel-Sipman M, Havenga C, Morgan N, de Winter J, Digweed M, Savoia A, Pronk J, de Ravel T, Jansen S, Joenje H, Gluckman E, Mathew CG
    Blood. 2000 ; 96 (13) : 4064-4070.
    PMID 11110674
     
    Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.
    Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, D'Andrea AD
    Molecular cell. 2001 ; 7 (2) : 249-262.
    PMID 11239454
     
    Fanconi anemia and DNA repair.
    Grompe M, D'Andrea A
    Human molecular genetics. 2001 ; 10 (20) : 2253-2259.
    PMID 11673408
     
    Localization of the Fanconi anemia complementation group D gene to a 200-kb region on chromosome 3p25.3.
    Hejna JA, Timmers CD, Reifsteck C, Bruun DA, Lucas LW, Jakobs PM, Toth-Fejel S, Unsworth N, Clemens SL, Garcia DK, Naylor SL, Thayer MJ, Olson SB, Grompe M, Moses RE
    American journal of human genetics. 2000 ; 66 (5) : 1540-1551.
    PMID 10762542
     
    Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway.
    Medhurst AL, Huber PA, Waisfisz Q, de Winter JP, Mathew CG
    Human molecular genetics. 2001 ; 10 (4) : 423-429.
    PMID 11157805
     
    Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner.
    Qiao F, Moss A, Kupfer GM
    The Journal of biological chemistry. 2001 ; 276 (26) : 23391-23396.
    PMID 11297559
     
    Positional cloning of a novel Fanconi anemia gene, FANCD2.
    Timmers C, Taniguchi T, Hejna J, Reifsteck C, Lucas L, Bruun D, Thayer M, Cox B, Olson S, D'Andrea AD, Moses R, Grompe M
    Molecular cell. 2001 ; 7 (2) : 241-248.
    PMID 11239453
     
    Microcell mediated chromosome transfer maps the Fanconi anaemia group D gene to chromosome 3p.
    Whitney M, Thayer M, Reifsteck C, Olson S, Smith L, Jakobs PM, Leach R, Naylor S, Joenje H, Grompe M
    Nature genetics. 1995 ; 11 (3) : 341-343.
    PMID 7581463
     
    The Chinese hamster FANCG/XRCC9 mutant NM3 fails to express the monoubiquitinated form of the FANCD2 protein, is hypersensitive to a range of DNA damaging agents and exhibits a normal level of spontaneous sister chromatid exchange.
    Wilson JB, Johnson MA, Stuckert AP, Trueman KL, May S, Bryant PE, Meyn RE, D'Andrea AD, Jones NJ
    Carcinogenesis. 2001 ; 22 (12) : 1939-1946.
    PMID 11751423
     
    Current knowledge on the pathophysiology of Fanconi anemia: from genes to phenotypes.
    Yamashita T, Nakahata T
    International journal of hematology. 2001 ; 74 (1) : 33-41.
    PMID 11530803
     
    Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9.
    Yang Y, Kuang Y, Montes De Oca R, Hays T, Moreau L, Lu N, Seed B, D'Andrea AD
    Blood. 2001 ; 98 (12) : 3435-3440.
    PMID 11719385
     

    Citation

    This paper should be referenced as such :
    Huret, JL
    FANCD2 (Fanconi anemia, complementation group D2)
    Atlas Genet Cytogenet Oncol Haematol. 2002;6(4):277-278.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/FADID103.html
    History of this paper:
    Huret, JL. FAD (Fanconi anaemia group D). Atlas Genet Cytogenet Oncol Haematol. 1998;2(3):83-83.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37433/04-1998-FAD.pdf

    Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 2 ]
      Fanconi anemia Familial Myeloproliferative Disorders

    External links

    Nomenclature
    HGNC (Hugo)FANCD2   3585
    LRG (Locus Reference Genomic)LRG_306
    Cards
    AtlasFADID103
    Entrez_Gene (NCBI)FANCD2  2177  Fanconi anemia complementation group D2
    AliasesFA-D2; FA4; FACD; FAD; 
    FAD2; FANCD
    GeneCards (Weizmann)FANCD2
    Ensembl hg19 (Hinxton)ENSG00000144554 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000144554 [Gene_View]  chr3:10026387-10101937 [Contig_View]  FANCD2 [Vega]
    ICGC DataPortalENSG00000144554
    TCGA cBioPortalFANCD2
    AceView (NCBI)FANCD2
    Genatlas (Paris)FANCD2
    WikiGenes2177
    SOURCE (Princeton)FANCD2
    Genetics Home Reference (NIH)FANCD2
    Genomic and cartography
    GoldenPath hg38 (UCSC)FANCD2  -     chr3:10026387-10101937 +  3p25.3   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)FANCD2  -     3p25.3   [Description]    (hg19-Feb_2009)
    EnsemblFANCD2 - 3p25.3 [CytoView hg19]  FANCD2 - 3p25.3 [CytoView hg38]
    Mapping of homologs : NCBIFANCD2 [Mapview hg19]  FANCD2 [Mapview hg38]
    OMIM189960   227646   613984   
    Gene and transcription
    Genbank (Entrez)AF230336 AF340183 AK022613 AK074406 AK307512
    RefSeq transcript (Entrez)NM_001018115 NM_001319984 NM_033084
    RefSeq genomic (Entrez)
    Consensus coding sequences : CCDS (NCBI)FANCD2
    Cluster EST : UnigeneHs.208388 [ NCBI ]
    CGAP (NCI)Hs.208388
    Alternative Splicing GalleryENSG00000144554
    Gene ExpressionFANCD2 [ NCBI-GEO ]   FANCD2 [ EBI - ARRAY_EXPRESS ]   FANCD2 [ SEEK ]   FANCD2 [ MEM ]
    Gene Expression Viewer (FireBrowse)FANCD2 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)2177
    GTEX Portal (Tissue expression)FANCD2
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ9BXW9   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtQ9BXW9  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ9BXW9
    Splice isoforms : SwissVarQ9BXW9
    PhosPhoSitePlusQ9BXW9
    Domains : Interpro (EBI)FANCD2   
    Domain families : Pfam (Sanger)FancD2 (PF14631)   
    Domain families : Pfam (NCBI)pfam14631   
    Conserved Domain (NCBI)FANCD2
    DMDM Disease mutations2177
    Blocks (Seattle)FANCD2
    SuperfamilyQ9BXW9
    Human Protein AtlasENSG00000144554
    Peptide AtlasQ9BXW9
    HPRD01968
    IPIIPI00075081   IPI00604399   IPI00604576   IPI00604753   IPI00925969   IPI00925767   
    Protein Interaction databases
    DIP (DOE-UCLA)Q9BXW9
    IntAct (EBI)Q9BXW9
    FunCoupENSG00000144554
    BioGRIDFANCD2
    STRING (EMBL)FANCD2
    ZODIACFANCD2
    Ontologies - Pathways
    QuickGOQ9BXW9
    Ontology : AmiGOcondensed chromosome  protein binding  nucleus  nucleoplasm  nucleolus  cytosol  DNA repair  synapsis  gamete generation  response to gamma radiation  nuclear body  cellular response to oxidative stress  interstrand cross-link repair  regulation of regulatory T cell differentiation  brain morphogenesis  regulation of inflammatory response  regulation of sequence-specific DNA binding transcription factor activity  DNA polymerase binding  neuronal stem cell population maintenance  regulation of CD40 signaling pathway  
    Ontology : EGO-EBIcondensed chromosome  protein binding  nucleus  nucleoplasm  nucleolus  cytosol  DNA repair  synapsis  gamete generation  response to gamma radiation  nuclear body  cellular response to oxidative stress  interstrand cross-link repair  regulation of regulatory T cell differentiation  brain morphogenesis  regulation of inflammatory response  regulation of sequence-specific DNA binding transcription factor activity  DNA polymerase binding  neuronal stem cell population maintenance  regulation of CD40 signaling pathway  
    Pathways : BIOCARTABRCA1-dependent Ub-ligase activity [Genes]    Role of BRCA1, BRCA2 and ATR in Cancer Susceptibility [Genes]   
    Pathways : KEGGFanconi anemia pathway   
    REACTOMEQ9BXW9 [protein]
    REACTOME PathwaysR-HSA-6796648 [pathway]   
    NDEx NetworkFANCD2
    Atlas of Cancer Signalling NetworkFANCD2
    Wikipedia pathwaysFANCD2
    Orthology - Evolution
    OrthoDB2177
    GeneTree (enSembl)ENSG00000144554
    Phylogenetic Trees/Animal Genes : TreeFamFANCD2
    HOVERGENQ9BXW9
    HOGENOMQ9BXW9
    Homologs : HomoloGeneFANCD2
    Homology/Alignments : Family Browser (UCSC)FANCD2
    Gene fusions - Rearrangements
    Fusion : MitelmanFANCD2/MTMR14 [3p25.3/3p25.3]  
    Fusion: TCGAFANCD2 3p25.3 MTMR14 3p25.3 BRCA
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerFANCD2 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)FANCD2
    dbVarFANCD2
    ClinVarFANCD2
    1000_GenomesFANCD2 
    Exome Variant ServerFANCD2
    ExAC (Exome Aggregation Consortium)FANCD2 (select the gene name)
    Genetic variants : HAPMAP2177
    Genomic Variants (DGV)FANCD2 [DGVbeta]
    DECIPHERFANCD2 [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisFANCD2 
    Mutations
    ICGC Data PortalFANCD2 
    TCGA Data PortalFANCD2 
    Broad Tumor PortalFANCD2
    OASIS PortalFANCD2 [ Somatic mutations - Copy number]
    Cancer Gene: CensusFANCD2 
    Somatic Mutations in Cancer : COSMICFANCD2  [overview]  [genome browser]  [tissue]  [distribution]  
    Mutations and Diseases : HGMDFANCD2
    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
    LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
    LOVD (Leiden Open Variation Database)Fanconi anemia database
    BioMutasearch FANCD2
    DgiDB (Drug Gene Interaction Database)FANCD2
    DoCM (Curated mutations)FANCD2 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)FANCD2 (select a term)
    intoGenFANCD2
    NCG5 (London)FANCD2
    Cancer3DFANCD2(select the gene name)
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM189960    227646    613984   
    Orphanet634   
    MedgenFANCD2
    Genetic Testing Registry FANCD2
    NextProtQ9BXW9 [Medical]
    TSGene2177
    GENETestsFANCD2
    Target ValidationFANCD2
    Huge Navigator FANCD2 [HugePedia]
    snp3D : Map Gene to Disease2177
    BioCentury BCIQFANCD2
    ClinGenFANCD2
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD2177
    Chemical/Pharm GKB GenePA27999
    Clinical trialFANCD2
    Miscellaneous
    canSAR (ICR)FANCD2 (select the gene name)
    Other databaseFanconi anemia mutation database
    Probes
    Litterature
    PubMed185 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineFANCD2
    EVEXFANCD2
    GoPubMedFANCD2
    iHOPFANCD2
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Fri Jun 30 11:06:28 CEST 2017
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