This report describes Fanconi anemia, complementation group D2 (FANCD2), which is a subtype of Fanconi anemia; FANCD2 exhibits autosomal recessive inheritance. The human gene implicated in this disease is FANCD2, which encodes Fanconi anemia complementation group D2, a protein required for the maintenance of chromosomal stability. There is one high-scoring fly ortholog, Fancd2, for which RNAi targeting constructs have been generated.
A UAS construct of the human Hsap\FANCD2 gene has been introduced into flies, but has not been characterized; a stock is available.
RNAi-effected reduction in expression of Dmel\Fancd2 results hypersensitivity to cross-linking agents; chromosome nondisjunction is observed in larval neuroblasts.
[updated Aug. 2022 by FlyBase; FBrf0222196]
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk of malignancy. Physical abnormalities, present in 60%-75% of affected individuals, include one or more of the following: short stature; abnormal skin pigmentation; malformations of the thumbs, forearms, skeletal system, eyes, kidneys and urinary tract, ears (and decreased hearing), heart, gastrointestinal system, central nervous system; hypogonadism; and developmental delay. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. By age 40 to 50 years, the estimated cumulative incidence of bone marrow failure is 90%; the incidence of hematologic malignancies (primarily acute myeloid leukemia) 10%-30%; and of nonhematologic malignancies (solid tumors, particularly of the head and neck, skin, GI tract, and genital tract) 25%-30%. [from GeneReviews, Fanconi Anemia, pubmed:20301575 2016.06.01]
Fanconi anemia is a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of FA is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair (summary by Deakyne and Mazin, 2011, pubmed:21568838). [From MIM:227650, 2016.05.26]
[FANCONI ANEMIA, COMPLEMENTATION GROUP D2; FANCD2](https://omim.org/entry/227646)
[FANCD2 GENE; FANCD2](https://omim.org/entry/613984)
Fanconi anemia, complementation group D2 (FANCD2) is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. [from UniProt, uniprot:Q9BXW9 2016.06.01]
Fanconi anemia of complementation group D2 (FANCD2) is caused by compound heterozygous or homozygous mutation in the FANCD2 gene [From MIM:227646, 2016.05.27]
The FANCD2 protein is required for maintenance of chromosomal stability. It promotes accurate and efficient pairing of homologous chromosomes during meiosis, and is involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. FANCD2 may participate in S phase and G2 phase checkpoint activation upon DNA damage. FANCD2 plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress. It is required for the targeting, or stabilization, of Bloom syndrome protein REQL3 (MIM:604610) to non-centromeric abnormal structures induced by replicative stress. FANCD2 promotes BRCA2/FANCD1 (MIM:600185) loading onto damaged chromatin. It may also be involved in B-cell immunoglobulin isotype switching. [from UniProt, uniprot:Q9BXW9 2016.06.01]
One to one: 1 human to 1 Drosophila.
Ortholog of human FANCD2 (1 Drosophila to 1 human).
Dmel\Fancd2 shares 24% identity and 44% similarity with human FANCD2.
