12Fanconi anemia (FA) is a unique DNA damage repair pathway. Almost twenty-two genes have 13 been identified which are associated with the FA pathway. Defect in any of those genes causes 14 genomic instability, and the patients bear the mutation become susceptible to cancer. In our 15 earlier work, we have identified that Fanconi anemia protein G (FANCG) protects the 16 mitochondria from oxidative stress. In this report, we have identified eight patients having 17 mutation (C.65G>C; p.Arg22Pro) in the N-terminal of FANCG. The mutant protein 18 hFANCGR22P is able to repair the DNA and able to retain the monoubiquitination of FANCD2 19 in FANCGR22P/FGR22P cell. However, it lost mitochondrial localization and failed to protect 20 mitochondria from oxidative stress. Mitochondrial instability in the FANCGR22P cell causes the 21 transcriptional down-regulation of mitochondrial iron-sulphur cluster biogenesis protein Frataxin 22 (FXN) and resulting iron deficiency of FA protein FANCJ, an iron-sulphur containing helicase 23 involved in DNA repair. 24 25 26 27 28 29 30 31 32 33 34 65 head and neck cancer (Rosenberg et al., 2005). To date, twenty two genes have been identified 66 that associate with FA that are primarily involved in a specific type of DNA damage repair; inter-67 strand crosslink (ICL) repair. ICL is caused by the exogenous alkylating agents or endogenous 68 130 tracker (pDsmito-Red) was used in these co-localization studies. Each deletion construct 131 including a wild type control was transiently expressed along with mito-tracker in HeLa cells. The 132 expression of both the constructs was analyzed by deconvolution microscope (Axio Observer.Z1, 133