FANCD2 (Fanconi anemia, complementation group D2)

2002-06-01   Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Identity

HGNC
LOCATION
3p25.3
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
FA-D2,FA4,FACD,FAD,FAD2,FANCD
FUSION GENES

DNA/RNA

Description

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

Proteins

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

    Entity name
    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 anaemias 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

    Pubmed IDLast YearTitleAuthors
    118541762002Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia.Callén E et al
    92925051997Molecular biology of Fanconi anemia: implications for diagnosis and therapy.D'Andrea AD et al
    111106742000Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group.Faivre L et al
    112394542001Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.Garcia-Higuera I et al
    116734082001Fanconi anemia and DNA repair.Grompe M et al
    107625422000Localization of the Fanconi anemia complementation group D gene to a 200-kb region on chromosome 3p25.3.Hejna JA et al
    111578052001Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway.Medhurst AL et al
    112975592001Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner.Qiao F et al
    112394532001Positional cloning of a novel Fanconi anemia gene, FANCD2.Timmers C et al
    75814631995Microcell mediated chromosome transfer maps the Fanconi anaemia group D gene to chromosome 3p.Whitney M et al
    117514232001The 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 et al
    115308032001Current knowledge on the pathophysiology of Fanconi anemia: from genes to phenotypes.Yamashita T et al
    117193852001Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9.Yang Y et al

    Other Information

    Locus ID:

    NCBI: 2177
    MIM: 613984
    HGNC: 3585
    Ensembl: ENSG00000144554

    Variants:

    dbSNP: 2177
    ClinVar: 2177
    TCGA: ENSG00000144554
    COSMIC: FANCD2

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000144554ENST00000287647Q9BXW9
    ENSG00000144554ENST00000383807Q9BXW9
    ENSG00000144554ENST00000383807A0A024R2G2
    ENSG00000144554ENST00000419585Q9BXW9
    ENSG00000144554ENST00000419585A0A024R2G2
    ENSG00000144554ENST00000421731H7BZJ7
    ENSG00000144554ENST00000431693Q9BXW9
    ENSG00000144554ENST00000435522F8WE37
    ENSG00000144554ENST00000625535F8WE37

    Expression (GTEx)

    0
    5
    10
    15
    20
    25
    30

    Pathways

    PathwaySourceExternal ID
    Fanconi anemia pathwayKEGGko03460
    Fanconi anemia pathwayKEGGhsa03460
    Gene ExpressionREACTOMER-HSA-74160
    Generic Transcription PathwayREACTOMER-HSA-212436
    Transcriptional Regulation by TP53REACTOMER-HSA-3700989
    DNA RepairREACTOMER-HSA-73894
    Fanconi Anemia PathwayREACTOMER-HSA-6783310
    TP53 Regulates Transcription of DNA Repair GenesREACTOMER-HSA-6796648

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    References

    Pubmed IDYearTitleCitations
    194659222009Replication stress induces sister-chromatid bridging at fragile site loci in mitosis.258
    122391512002S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51.195
    156500502005Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair.170
    153140222004ATR couples FANCD2 monoubiquitination to the DNA-damage response.159
    206030152010Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2.150
    206711562010FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair.127
    205389112010Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway.124
    265840492015The Fanconi Anemia Pathway Protects Genome Integrity from R-loops.88
    149887232004The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR-NBS1-FANCD2 pathways.85
    154544912005Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin.71

    Citation

    Jean-Loup Huret

    FANCD2 (Fanconi anemia, complementation group D2)

    Atlas Genet Cytogenet Oncol Haematol. 2002-06-01

    Online version: http://atlasgeneticsoncology.org/gene/103/fancd2

    Historical Card

    1998-04-01 FANCD2 (Fanconi anemia, complementation group D2) by  Jean-Loup Huret 

    Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France