Fanconi anemia complementation group C (FANCC) (FANCC)

Fanconi anemia complementation group C (FANCC) is a critical protein involved in the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links (ICLs) [1, 2]. It functions as a core component of the multi-subunit FA core complex, which acts as an E3 ubiquitin ligase to monoubiquitinate the FANCD2 and FANCI proteins, a key step in activating the DNA repair cascade [1, 4]. In CD34+ hematopoietic stem/progenitor cells (HSPCs), FANCC is vital for maintaining genomic stability and preventing hypersensitivity to pro-inflammatory cytokines like interferon-gamma and tumor necrosis factor-alpha, which can trigger premature apoptosis and lead to bone marrow failure [3, 4]. Mutations in the FANCC gene are responsible for Fanconi anemia complementation group C, a rare genetic disorder characterized by progressive bone marrow failure, physical abnormalities, and a high risk of developing acute myeloid leukemia and other cancers [2, 4]. Therapeutic strategies targeting FANCC in CD34+ cells primarily focus on ex vivo gene therapy, where functional copies of the FANCC gene are delivered via lentiviral or retroviral vectors to restore DNA repair capacity and hematopoiesis [3]. Monitoring for successful gene integration and the absence of clonal dominance is essential for the safety and efficacy of these treatments [3].

Other names

FACCFA3Fanconi anemia group C proteinProtein FAC

Gene replacement therapy to restore functional DNA repair mechanisms in hematopoietic stem cells.