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Target intelligence / Profile preview
FANCD2 and FANCI associated nuclease 1 (FAN1)
- Target
- FAN1
- Molecular classification
- Enzyme, DNA repair nuclease, Virus-type replication-repair nuclease (VRR_nuc), Flap endonuclease
01
Overview
FANCD2 and FANCI associated nuclease 1 (FAN1) is a structure-specific DNA repair enzyme required for the repair of DNA interstrand cross-links, acting as a 5'-flap endonuclease and 5'-3' exonuclease. It is recruited to damage sites by monoubiquitinated FANCD2 via the Fanconi anemia pathway, where it cleaves various DNA intermediates to restore DNA integrity. Genetic deficiencies or variants in FAN1 are linked to kidney disease (karyomegalic interstitial nephritis), neurodevelopmental disorders, and increased sensitivity to DNA-damaging agents.
- Other names
- Fanconi-associated nuclease 1KIAA1018FANCD2-FANCI-associated nuclease 1
02
Mechanism of action
Agents targeting DNA cross-link repair act by inducing DNA lesions that require FAN1-mediated repair; loss of FAN1 increases sensitivity to these agents. Experimental: targeting FAN1 mRNA by siRNA or antisense for research/trials
03
Biological functions
DNA repairInterstrand cross-link repairProtection against DNA damageCell cycle regulationMaintenance of genome stability
04
Disease associations
Cancer (dysregulation of repair and genomic instability)Karyomegalic interstitial nephritis (KIN)Neuropsychiatric conditions (autism/schizophrenia associations)Other DNA repair disorders
05
Safety considerations
Loss-of-function increases DNA damage, risk of nephritis, and genomic instabilityPotential increased neuropsychiatric risk with loss-of-function variants
06
Interacting drugs
Mitomycin C
2 more in the full profile.
07
Biomarkers
FAN1 mutation status (for KIN; possible relevance to chemotherapeutic response)
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