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
11854176	2002	Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia.	Callén E et al
11093276	2000	Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9.	Demuth I et al
11110674	2000	Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group.	Faivre L et al
11756225	2002	The FANCG Fanconi anemia protein interacts with CYP2E1: possible role in protection against oxidative DNA damage.	Futaki M et al
11181053	2001	Fanconi anemia protein, FANCG, is a phosphoprotein and is upregulated with FANCA after TNF-alpha treatment.	Futaki M et al
11239454	2001	Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.	Garcia-Higuera I et al
11673408	2001	Fanconi anemia and DNA repair.	Grompe M et al
11823446	2002	Reduced fertility and hypersensitivity to mitomycin C characterize Fancg/Xrcc9 null mice.	Koomen M et al
10961856	2000	Carboxy terminal region of the Fanconi anemia protein, FANCG/XRCC9, is required for functional activity.	Kuang Y et al
9256465	1997	The human XRCC9 gene corrects chromosomal instability and mutagen sensitivities in CHO UV40 cells.	Liu N et al
11157805	2001	Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway.	Medhurst AL et al
11438206	2001	Functional analysis of patient-derived mutations in the Fanconi anemia gene, FANCG/XRCC9.	Nakanishi K et al
11297559	2001	Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner.	Qiao F et al
10468606	1999	A physical complex of the Fanconi anemia proteins FANCG/XRCC9 and FANCA.	Waisfisz Q et al
11751423	2001	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 et al
11530803	2001	Current knowledge on the pathophysiology of Fanconi anemia: from genes to phenotypes.	Yamashita T et al
11719385	2001	Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9.	Yang Y et al
9806548	1998	The 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 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
34864095	2022	In silico study of missense variants of FANCA, FANCC and FANCG genes reveals high risk deleterious alleles predisposing to Fanconi anemia pathogenesis.	1
34864095	2022	In silico study of missense variants of FANCA, FANCC and FANCG genes reveals high risk deleterious alleles predisposing to Fanconi anemia pathogenesis.	1
32947577	2021	Clinical and Genetic Features of Patients With Fanconi Anemia in Lebanon and Report on Novel Mutations in the FANCA and FANCG Genes.	1
33394227	2021	Severe telomere shortening in Fanconi anemia complementation group L.	3
34436527	2021	Frequent internuclear bridging in a Fanconi anemia patient with FANCG mutation.	0
32947577	2021	Clinical and Genetic Features of Patients With Fanconi Anemia in Lebanon and Report on Novel Mutations in the FANCA and FANCG Genes.	1
33394227	2021	Severe telomere shortening in Fanconi anemia complementation group L.	3
34436527	2021	Frequent internuclear bridging in a Fanconi anemia patient with FANCG mutation.	0
32529760	2020	Endocrine profiling in patients with Fanconi anemia, homozygous for a FANCG founder mutation.	4
32989015	2020	Loss of Mitochondrial Localization of Human FANCG Causes Defective FANCJ Helicase.	2
32529760	2020	Endocrine profiling in patients with Fanconi anemia, homozygous for a FANCG founder mutation.	4
32989015	2020	Loss of Mitochondrial Localization of Human FANCG Causes Defective FANCJ Helicase.	2
29843852	2018	Fanconi anaemia in South Africa: Past, present and future.	2
30057198	2018	FANCA Promotes DNA Double-Strand Break Repair by Catalyzing Single-Strand Annealing and Strand Exchange.	48
29843852	2018	Fanconi anaemia in South Africa: Past, present and future.	2

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/deep-insight-explorer/cancer-prone-explorer/teaching-explorer/