FANCC (Fanconi anaemia complementation group C)

2012-07-01   Hemantika Dasgupta , Chinmay Kumar Panda 

Chittaranjan National Cancer Institute, 37, S P Mukherjee Road, Kolkata 700026, India


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



14 exons; spans 80 kb.


mRNA of 2.3, 3.2, and 4.6 kb (alternative splicing in 5, variable 3 untranslated region, exon 13 skipping).



558 amino acids; 63 kDa.


Wide, in particular in the bones; high expression in proliferating cells, low in differentiated cells.


Cytoplasmic (mostly) and nuclear.


- 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.
- FANCC may have mutlifunctional roles, in addition to its involvement in the FA pathway. FANCC binds to cdc2 (mitotic cyclin-dependent kinase), STAT1, GRP94 (a chaperon protein), NADPH, and a number of other proteins; involved in DNA repair and in suppressing interferon gamma induced cellular apoptosis.
There are 15 FA genes that make up the FA pathway. Among these FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCM and FANCL form the core complex. During G1 phase of cell cycle these proteins are localized in the cytoplasm. During S phase or during DNA damage FANCA and FANCG at first form a complex in the cytoplasm followed by its interaction with FANCC. Then the complex translocates to the nucleus. In the nucleus other FA proteins like FANCE, F, B, M and L interact with the complex. They cooperatively bind to form the core complex. FANCL has E3 ubiquitin ligase activity. The core complex then activates FANCD2 and FANCI by monoubiquitination. The activated FANCD2-FANCI complex then interact with other FA genes like FANCP/SLX4, FANCD1/BRCA2, FANCJ/BRIP1 and FANCN/PALB2 for efficient DNA repair.
FANCC helps in accumulation of FANCE and it has role in foci formation of MRE11/RAD50/NBS1 complex in response to intrastrand crosslink inducers.
FANCC binds to cdc2 (mitotic cyclin-dependent kinase), it is necessary for DNA damage-induced G2/M checkpoint in vitro and in vivo.
In response to oxidative DNA damage, FANCC prevents premature senescence in hematopoietic stem cells. It interacts with cytochrome p-450 reductase and NADPH during increased production of reactive oxygen species (ROS).
In hematopoietic stem cells it regulates apoptosis, self renewal capacity and cell cycle control. It inhibits activity of dsRNA dependent protein kinase mediated death signaling pathway by interacting with Hsp70. FANCC and p53 cooperatively work in apoptosis. It has role in suppressing interferon gamma induced cellular apoptosis.
In normal oral epithelium, a gradual increase of FANCC protein expression from basal to parabasal layer to spinous layer suggesting its role in cellular proliferation and differentiation.
FANCC is important for proper functioning of monocytes/macrophages. It suppresses TNFα production in mononuclear phagocytes by suppressing TLR8 activity.
FANCC interacts with STAT1, GRP94 (a chaperon protein). It has role in telomere attrition and telomere recombination.


No known homology.



Most mutations are found in exon1, intron 4, and exon 14.

Implicated in

Entity name
Fanconi anaemia (FA)
FACC is implicated in the FA complementation group C; it represents about 15% of FA cases.
Fanconi anaemia is a chromosome instability syndrome/cancer prone disease (at risk of leukaemia).
- Fanconi anaemias prognosis is poor; mean survival is 16 years: patients die of bone marrow failure (infections, haemorrhages), leukaemia, or androgen therapy related liver tumours.
- It has recently been shown that significant phenotypic differences were found between the various complementation groups. FA group C patients had less somatic abnormalities. However, there is a certain clinical heterogeneity.
Spontaneous,chromatid/chromosome breaks; increased rate of breaks compared to control, when induced by breaking agent.
Hybrid gene
Mutations in exon 4, 13 leading to deletion of exon 9 were reported in Brazilian Fanconi Anemia patients.
Fanconi anemia patients are prone to develop head and neck, esophageal, gastrointestinal, vulvar and anal cancers.
Frequent deletion and promoter methylation are observed in FANCC gene in oral cancer, breast cancer, acute leukemia and pancreatic cancer.
Entity name
Diabetes and obesity
FANCC prevents diabetes and obesity.


Pubmed IDLast YearTitleAuthors
222346992012p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC- and FANCA-deficient mononuclear phagocytes.Anur P et al
195366492009The Fanconi anemia family of genes and its correlation with breast cancer susceptibility and breast cancer features.Barroso E et al
179090712007Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer.Berwick M et al
146252942004Regulation of the Fanconi anemia group C protein through proteolytic modification.Brodeur I et al
118541762002Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia.Callén E et al
156953772005Germ line Fanconi anemia complementation group C mutations and pancreatic cancer.Couch FJ 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
128555572003Fanconi anemia type C and p53 cooperate in apoptosis and tumorigenesis.Freie B et al
153776542004A role for the Fanconi anemia C protein in maintaining the DNA damage-induced G2 checkpoint.Freie BW et al
112394542001Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.Garcia-Higuera I et al
218612282012Association of FANCC and PTCH1 with the development of early dysplastic lesions of the head and neck.Ghosh A et al
84906201993Characterisation of the exon structure of the Fanconi anaemia group C gene by vectorette PCR.Gibson RA et al
161271712005FANCC, FANCE, and FANCD2 form a ternary complex essential to the integrity of the Fanconi anemia DNA damage response pathway.Gordon SM et al
116734082001Fanconi anemia and DNA repair.Grompe M et al
160206922005Lack of self-renewal capacity in Fancc-/- stem cells after ex vivo expansion.Habi O et al
205549742010Human FANCC is hypomorphic in murine Fancc-deficient cells.Hays LE et al
186070652008Hypermethylation of the FANCC and FANCL promoter regions in sporadic acute leukaemia.Hess CJ et al
156165722005Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM.Hirano S et al
226756172012Towards a molecular understanding of the fanconi anemia core complex.Hodson C et al
216978912011Upregulation of Fanconi anemia DNA repair genes in melanoma compared with non-melanoma skin cancer.Kao WH et al
174315032007Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated.Kennedy RD et al
216709572012Association of FANCC polymorphisms with FEV1 decline in aspirin exacerbated respiratory disease.Kim JH et al
215730162011FANCD1/BRCA2 plays predominant role in the repair of DNA damage induced by ACNU or TMZ.Kondo N et al
165134312006The nuclear accumulation of the Fanconi anemia protein FANCE depends on FANCC.Léveillé F et al
224828912012Fanconi anemia links reactive oxygen species to insulin resistance and obesity.Li J et al
221060092012Impaired function of Fanconi anemia type C-deficient macrophages.Liu Y et al
167208392006Evidence for subcomplexes in the Fanconi anemia pathway.Medhurst AL et al
153277762004The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair.Niedzwiedz W et al
127669482003Fanconi anaemia proteins: major roles in cell protection against oxidative damage.Pagano G et al
205098602010Genetic inactivation of the Fanconi anemia gene FANCC identified in the hepatocellular carcinoma cell line HuH-7 confers sensitivity towards DNA-interstrand crosslinking agents.Palagyi A et al
123970612002The anti-apoptotic function of Hsp70 in the interferon-inducible double-stranded RNA-dependent protein kinase-mediated death signaling pathway requires the Fanconi anemia protein, FANCC.Pang Q et al
123547792002DNA cross-link-dependent RAD50/MRE11/NBS1 subnuclear assembly requires the Fanconi anemia C protein.Pichierri P 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
200228862010FANCC suppresses short telomere-initiated telomere sister chromatid exchange.Rhee DB et al
180564342007Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde.Ridpath JR et al
189902332008Alterations in candidate genes PHF2, FANCC, PTCH1 and XPA at chromosomal 9q22.3 region: pathological significance in early- and late-onset breast carcinoma.Sinha S et al
15741151992Cloning of cDNAs for Fanconi's anaemia by functional complementation.Strathdee CA et al
128879092003BRCA1-independent ubiquitination of FANCD2.Vandenberg CJ et al
198507432009TLR8-dependent TNF-(alpha) overexpression in Fanconi anemia group C cells.Vanderwerf SM et al
115308032001Current knowledge on the pathophysiology of Fanconi anemia: from genes to phenotypes.Yamashita T et al
164294062006Novel inactivating mutations of FANCC in Brazilian patients with Fanconi anemia.Yates J et al
150771702004Fanconi anemia C gene product regulates expression of genes involved in differentiation and inflammation.Zanier R et al
174058152007Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescence.Zhang X et al

Other Information

Locus ID:

NCBI: 2176
MIM: 613899
HGNC: 3584
Ensembl: ENSG00000158169


dbSNP: 2176
ClinVar: 2176
TCGA: ENSG00000158169


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Fanconi anemia pathwayKEGGko03460
Fanconi anemia pathwayKEGGhsa03460
FA core complexKEGGhsa_M00413
FA core complexKEGGM00413
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
Fanconi Anemia PathwayREACTOMER-HSA-6783310
TP53 Regulates Transcription of DNA Repair GenesREACTOMER-HSA-6796648

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
153277762004The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair.131
205389112010Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway.124
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
230283382012Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles.68
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
156165722005Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM.51
156953772005Germ line Fanconi anemia complementation group C mutations and pancreatic cancer.42
255458962015Fanconi anemia gene editing by the CRISPR/Cas9 system.33
123970612002The anti-apoptotic function of Hsp70 in the interferon-inducible double-stranded RNA-dependent protein kinase-mediated death signaling pathway requires the Fanconi anemia protein, FANCC.32
152564252005The Fanconi anemia core complex associates with chromatin during S phase.22


Hemantika Dasgupta ; Chinmay Kumar Panda

FANCC (Fanconi anaemia complementation group C)

Atlas Genet Cytogenet Oncol Haematol. 2012-07-01

Online version:

Historical Card

2002-06-01 FANCC (Fanconi anaemia complementation group C) by  Jean-Loup Huret 

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

1998-02-01 FANCC (Fanconi anaemia complementation group C) by  Jean-Loup Huret 

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