FANCF (Fanconi anemia, complementation group F)

2002-06-01 Jean-Loup Huret Affiliation

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

Identity

HGNC

FANCF

LOCATION

11p14.3

IMAGE

LEGEND

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

LOCUSID

2188

ALIAS

FAF

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

1 exon; 1124 bp open reading frame

Proteins

Expression

weak;

Localisation

predominantly nuclear

Function

part of the FA complex with FANCA, FANCC, FANCE, 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, 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

ROM (prokaryote)

Implicated in

Entity name

Fanconi anaemia (FA); FANCF is implicated in the FA complementation group F; it represents about 2-3% 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. 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 ID	Last Year	Title	Authors
11854176	2002	Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia.	Callén E 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
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
11739191	2001	Correction of cross-linker sensitivity of Fanconi anemia group F cells by CD33-mediated protein transfer.	Holmes RK et al
11157805	2001	Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway.	Medhurst AL 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
11750104	2001	Function of the Fanconi anemia pathway in Fanconi anemia complementation group F and D1 cells.	Siddique MA et al
11530803	2001	Current knowledge on the pathophysiology of Fanconi anemia: from genes to phenotypes.	Yamashita T et al
11063725	2000	The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG.	de Winter JP et al

Other Information

Locus ID:

NCBI: 2188
MIM: 613897
HGNC: 3587
Ensembl: ENSG00000183161

Variants:

dbSNP: 2188
ClinVar: 2188
TCGA: ENSG00000183161
COSMIC: FANCF

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000183161	ENST00000327470	Q9NPI8
ENSG00000183161	ENST00000327470	A3KME0

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

References

Pubmed ID	Year	Title	Citations
14647419	2004	Inactivation of the Fanconi anemia/BRCA pathway in lung and oral cancers: implications for treatment and survival.	70
15126331	2004	Promoter hypermethylation of FANCF: disruption of Fanconi Anemia-BRCA pathway in cervical cancer.	58
17932744	2008	Estrogen receptor alpha, BRCA1, and FANCF promoter methylation occur in distinct subsets of sporadic breast cancers.	35
16418574	2006	Promoter hypermethylation of FANCF plays an important role in the occurrence of ovarian cancer through disrupting Fanconi anemia-BRCA pathway.	22
15262960	2004	The Fanconi anemia gene product FANCF is a flexible adaptor protein.	19
17082180	2007	Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complex.	19
18414472	2008	Promoter hypermethylation of FANCF and outcome in advanced ovarian cancer.	14
19536649	2009	The Fanconi anemia family of genes and its correlation with breast cancer susceptibility and breast cancer features.	13
20496165	2011	Comprehensive screen of genetic variation in DNA repair pathway genes and postmenopausal breast cancer risk.	12
19801548	2009	The interferon consensus sequence binding protein (ICSBP/IRF8) activates transcription of the FANCF gene during myeloid differentiation.	10

Citation

Jean-Loup Huret

FANCF (Fanconi anemia, complementation group F)

Atlas Genet Cytogenet Oncol Haematol. 2002-06-01

Online version: http://atlasgeneticsoncology.org/gene/294/fancf-(fanconi-anemia-complementation-group-f)