FANCG (Fanconi anemia, complementation group G)

2002-06-01 Jean-Loup Huret Affiliation

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

Identity

HGNC

FANCG

LOCATION

9p13.3

IMAGE

LEGEND

Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

LOCUSID

2189

ALIAS

FAG,XRCC9

FUSION GENES

Show Gene Fusions

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 ID	Last Year	Title	Authors

Other Information

Locus ID:

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

Variants:

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

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000221829	ENST00000378643	O15287
ENSG00000221829	ENST00000378643	Q53XM5
ENSG00000221829	ENST00000425676	F8WC08
ENSG00000221829	ENST00000448890	C9JSE3

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Fanconi anemia pathway	KEGG	ko03460
Fanconi anemia pathway	KEGG	hsa03460
FA core complex	KEGG	hsa_M00413
FA core complex	KEGG	M00413
DNA Repair	REACTOME	R-HSA-73894
Fanconi Anemia Pathway	REACTOME	R-HSA-6783310

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
16195237	2006	Polymorphisms of DNA repair genes and risk of non-small cell lung cancer.	112
19913121	2009	Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.	85
16609022	2006	Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer.	71
12861027	2003	Fanconi anemia FANCG protein in mitigating radiation- and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells.	50
18212739	2008	FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3.	40
20403997	2010	Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer.	30
15138265	2004	Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins.	27
19861517	2009	Predisposition for TMPRSS2-ERG fusion in prostate cancer by variants in DNA repair genes.	26
19339270	2009	Genetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 European countries: the ARCAGE project.	24
12915460	2003	Direct 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/haematological-explorer/gene-fusions/?id=295