Fanconi anemia complementation group A (FANCA) (FANCA)

Fanconi anemia complementation group A (FANCA) is a protein that serves as a vital component of the Fanconi anemia (FA) core complex, which is essential for the repair of DNA interstrand cross-links (ICLs) (Source: UniProt O15360). The FA core complex acts as an E3 ubiquitin ligase that monoubiquitinates the FANCD2 and FANCI proteins, a pivotal step in the FA pathway that recruits downstream nucleases and recombinases to sites of DNA damage (Source: PubMed PMID: 28234359). Mutations in the FANCA gene account for approximately 60-70% of Fanconi anemia cases, leading to a syndrome characterized by progressive bone marrow failure, congenital abnormalities, and a significantly increased predisposition to cancers, particularly acute myeloid leukemia (Source: NIH GeneReviews). In hematopoietic stem cells, FANCA deficiency results in the accumulation of DNA damage and hypersensitivity to cross-linking agents, eventually causing stem cell exhaustion (Source: PubMed PMID: 31534203). Current therapeutic interventions focus on ex vivo lentiviral gene therapy, such as RP-L102, to restore functional FANCA expression in the patient's own hematopoietic stem cells, aiming to provide a long-term cure for the hematologic manifestations of the disease (Source: Rocket Pharmaceuticals).

Other names

FA1FAAFACAFANCHFanconi anemia, complementation group A

Gene replacement therapy aims to deliver a functional copy of the FANCA gene into hematopoietic stem cells, restoring the ability of the Fanconi anemia core complex to monoubiquitinate FANCD2 and FANCI, thereby enabling DNA interstrand cross-link repair (Source: PubMed PMID: 31534203).