Fanconi anemia complementation group L (FANCL)

Fanconi anemia complementation group L (FANCL) is a critical E3 ubiquitin ligase that serves as the catalytic subunit of the Fanconi anemia (FA) core complex. Its primary biological function is the monoubiquitination of the FANCD2 and FANCI proteins, a pivotal signaling step in the FA pathway required for the repair of DNA interstrand cross-links (ICLs). Mutations in the FANCL gene are a known cause of Fanconi anemia, a rare genetic disorder characterized by progressive bone marrow failure, congenital malformations, and a significantly increased risk of developing malignancies such as acute myeloid leukemia and various solid tumors. In the context of oncology, FANCL is increasingly recognized as a therapeutic target; somatic alterations in FANCL can sensitize cancer cells to PARP inhibitors through a mechanism of synthetic lethality, similar to BRCA1/2 deficiencies. Furthermore, research is ongoing into small-molecule inhibitors of the FANCL-mediated ubiquitination process to potentially sensitize tumors to conventional DNA-damaging chemotherapies like cisplatin and mitomycin C.

Other names

E3 ubiquitin-protein ligase FANCLPHF9POGFAAP43Fanconi anemia group L proteinRING-type E3 ubiquitin transferase FANCLPHD finger protein 9

Synthetic lethality (PARP inhibition in FANCL-deficient cells); Sensitization to DNA-damaging agents via FA pathway inhibition