FANCD2 (Fanconi anemia, complementation group D2)
2002-06-01 Jean-Loup Huret AffiliationGenetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Identity
HGNC
LOCATION
3p25.3
IMAGE
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
FA-D2,FA4,FACD,FAD,FAD2,FANCD
FUSION GENES
DNA/RNA
Description
44 exons; 4356 bp open reading frame; the first exon is non-coding.
Proteins
Expression
weak
Localisation
nucleus
Function
the FA complex is comprised of : FANCA, FANCC, FANCE, FANCF, 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 (i.e. FANCD2-L), 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 (FANCD2-S).
FANCD2co-localizes with BRCA1 in DNA damaged-induced loci and in the synaptonemal complex of meotic chromosomes as well.
Homology
significant homologies can be found with proteins from various species
Implicated in
Entity name
Fanconi anaemia (FA); FANCD2 is implicated in the FA complementation group D, a heterogeneous group, with at least 2 genes: FANCD2, and a yet undiscovered FANCD1. FA complementation group D represents about 1% of FA cases. In FA complementation group D patients, the FA complex is normal, in contrast with results found in group A, B (with a yet unknown gene), C, E, F, and G patients.
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).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11854176 | 2002 | Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia. | Callén E et al |
| 9292505 | 1997 | Molecular biology of Fanconi anemia: implications for diagnosis and therapy. | D'Andrea AD 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 |
| 10762542 | 2000 | Localization of the Fanconi anemia complementation group D gene to a 200-kb region on chromosome 3p25.3. | Hejna JA 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 |
| 11239453 | 2001 | Positional cloning of a novel Fanconi anemia gene, FANCD2. | Timmers C et al |
| 7581463 | 1995 | Microcell mediated chromosome transfer maps the Fanconi anaemia group D gene to chromosome 3p. | Whitney M 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 |
Other Information
Locus ID:
NCBI: 2177
MIM: 613984
HGNC: 3585
Ensembl: ENSG00000144554
Variants:
dbSNP: 2177
ClinVar: 2177
TCGA: ENSG00000144554
COSMIC: FANCD2
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38229567 | 2024 | FANCD2 deficiency sensitizes SHH medulloblastoma to radiotherapy via ferroptosis. | 1 |
| 38443946 | 2024 | Pancancer analysis of the prognostic and immunological role of FANCD2: a potential target for carcinogenesis and survival. | 3 |
| 38229567 | 2024 | FANCD2 deficiency sensitizes SHH medulloblastoma to radiotherapy via ferroptosis. | 1 |
| 38443946 | 2024 | Pancancer analysis of the prognostic and immunological role of FANCD2: a potential target for carcinogenesis and survival. | 3 |
| 36814203 | 2023 | FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma. | 8 |
| 37526271 | 2023 | FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability. | 5 |
| 37591242 | 2023 | FBXL12 degrades FANCD2 to regulate replication recovery and promote cancer cell survival under conditions of replication stress. | 0 |
| 37599085 | 2023 | LncRNA SNHG1 upregulates FANCD2 and G6PD to suppress ferroptosis by sponging miR-199a-5p/3p in hepatocellular carcinoma. | 4 |
| 37777152 | 2023 | Mitotic DNA Synthesis in Untransformed Human Cells Preserves Common Fragile Site Stability via a FANCD2-Driven Mechanism That Requires HELQ. | 1 |
| 37821996 | 2023 | FANCD2 as a novel prognostic biomarker correlated with immune and drug therapy in Hepatitis B-related hepatocellular carcinoma. | 2 |
| 38060446 | 2023 | FANCD2-dependent mitotic DNA synthesis relies on PCNA K164 ubiquitination. | 3 |
| 36814203 | 2023 | FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma. | 8 |
| 37526271 | 2023 | FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability. | 5 |
| 37591242 | 2023 | FBXL12 degrades FANCD2 to regulate replication recovery and promote cancer cell survival under conditions of replication stress. | 0 |
| 37599085 | 2023 | LncRNA SNHG1 upregulates FANCD2 and G6PD to suppress ferroptosis by sponging miR-199a-5p/3p in hepatocellular carcinoma. | 4 |
Citation
Jean-Loup Huret
FANCD2 (Fanconi anemia, complementation group D2)
Atlas Genet Cytogenet Oncol Haematol. 2002-06-01
Online version: http://atlasgeneticsoncology.org/gene/103/fancd2
Historical Card
1998-04-01 FANCD2 (Fanconi anemia, complementation group D2) by Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
