FANCG (Fanconi anemia, complementation group G)

2002-06-01   Jean-Loup Huret 

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

Identity

HGNC
LOCATION
9p13.3
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
FAG,XRCC9
FUSION GENES

DNA/RNA

Description

14 exons; 1869 bp open reading frame

Transcription

2.2 and 2.5 kb

Proteins

Description

622 amino acids, 69 kDa; contains a leucine zipper; can be phosphorylated

Expression

weak; testis, thymus, lymphoblasts.

Localisation

predominantly nuclear

Function

part of the FA complex with FANCA, FANCC, FANCE, and FANCF; 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, 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.
  • Homology

    no known homology

    Mutations

    Germinal

    wide range of mutations (splice, nonsense, missense)

    Implicated in

    Entity name
    Fanconi anaemia (FA); FANCG is implicated in the FA complementation group G; it represents about 10% of FA cases.
    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. FA group G patients had more severe cytopenia and a higher incidence of leukemia. FA group G patients patients are high-risk groups with a poor hematologic outcome and should be considered as candidates both for frequent monitoring and early therapeutic intervention.
  • 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
    110932762000Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9.Demuth I et al
    111106742000Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group.Faivre L et al
    117562252002The FANCG Fanconi anemia protein interacts with CYP2E1: possible role in protection against oxidative DNA damage.Futaki M et al
    111810532001Fanconi anemia protein, FANCG, is a phosphoprotein and is upregulated with FANCA after TNF-alpha treatment.Futaki M 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
    118234462002Reduced fertility and hypersensitivity to mitomycin C characterize Fancg/Xrcc9 null mice.Koomen M et al
    109618562000Carboxy terminal region of the Fanconi anemia protein, FANCG/XRCC9, is required for functional activity.Kuang Y et al
    92564651997The human XRCC9 gene corrects chromosomal instability and mutagen sensitivities in CHO UV40 cells.Liu N et al
    111578052001Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway.Medhurst AL et al
    114382062001Functional analysis of patient-derived mutations in the Fanconi anemia gene, FANCG/XRCC9.Nakanishi K 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
    104686061999A physical complex of the Fanconi anemia proteins FANCG/XRCC9 and FANCA.Waisfisz Q 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
    98065481998The Fanconi anaemia group G gene FANCG is identical with XRCC9.de Winter JP et al

    Other Information

    Locus ID:

    NCBI: 2189
    MIM: 602956
    HGNC: 3588
    Ensembl: ENSG00000221829

    Variants:

    dbSNP: 2189
    ClinVar: 2189
    TCGA: ENSG00000221829
    COSMIC: FANCG

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000221829ENST00000378643O15287
    ENSG00000221829ENST00000378643Q53XM5
    ENSG00000221829ENST00000425676F8WC08
    ENSG00000221829ENST00000448890C9JSE3

    Expression (GTEx)

    0
    5
    10
    15
    20
    25
    30
    35

    Pathways

    PathwaySourceExternal ID
    Fanconi anemia pathwayKEGGko03460
    Fanconi anemia pathwayKEGGhsa03460
    FA core complexKEGGhsa_M00413
    FA core complexKEGGM00413
    DNA RepairREACTOMER-HSA-73894
    Fanconi Anemia PathwayREACTOMER-HSA-6783310

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    References

    Pubmed IDYearTitleCitations
    161952372006Polymorphisms of DNA repair genes and risk of non-small cell lung cancer.112
    199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
    166090222006Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer.71
    128610272003Fanconi anemia FANCG protein in mitigating radiation- and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells.50
    182127392008FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3.40
    204039972010Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer.30
    151382652004Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins.27
    198615172009Predisposition for TMPRSS2-ERG fusion in prostate cancer by variants in DNA repair genes.26
    193392702009Genetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 European countries: the ARCAGE project.24
    129154602003Direct interaction of the Fanconi anaemia protein FANCG with BRCA2/FANCD1.23

    Citation

    Jean-Loup Huret

    FANCG (Fanconi anemia, complementation group G)

    Atlas Genet Cytogenet Oncol Haematol. 2002-06-01

    Online version: http://atlasgeneticsoncology.org/gene/295/fancg