Fanconi anemia complementation group C (FANCC)

Fanconi anemia complementation group C (FANCC) is a protein-coding gene essential for the maintenance of genomic stability through the Fanconi anemia (FA) pathway (UniProt P24298). The FANCC protein acts as a critical member of the FA core complex, which is responsible for the monoubiquitination of the FANCD2 and FANCI proteins, a vital step in repairing DNA interstrand cross-links (PubMed: 22058134). Mutations in the FANCC gene result in Fanconi anemia type C, a rare genetic disorder characterized by progressive bone marrow failure, physical abnormalities, and a significantly increased risk of developing leukemia and solid tumors (NIH GARD). In therapeutic contexts, autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) are harvested from the patient and modified ex vivo to express a functional FANCC gene, typically using lentiviral vectors (PubMed: 28935643). This gene therapy approach aims to provide a permanent source of functional blood cells, thereby bypassing the need for allogeneic stem cell transplantation and its associated risks like graft-versus-host disease (PubMed: 31534167). Successful engraftment of these modified cells restores the DNA repair capacity of the hematopoietic system, potentially halting the progression of bone marrow failure (PubMed: 10506430).

Other names

FACCFA3Fanconi anemia group C proteinProtein FAC

Gene replacement therapy involving the ex vivo transduction of autologous CD34+ hematopoietic stem cells with a functional FANCC transgene to restore DNA repair mechanisms and prevent bone marrow failure.