Loss of the human BRIP1 C terminus does not cause Fanconi anemia.

Loss of the human BRIP1 C terminus does not cause Fanconi anemia, even with homozygous truncating variants.

• Why it matters: Fanconi anemia is linked to DNA repair defects, but the role of BRIP1's C-terminal region in FA development was unclear, raising questions about its necessity for disease manifestation.
• What they did: Researchers identified 11 individuals with homozygous truncating variants in BRIP1's C terminus, analyzed patient-derived cells, and used isogenic cell models to assess ICL sensitivity and protein stability.
• The result: Loss of BRIP1's C-terminal region does not produce FA symptoms or ICL sensitivity, indicating that FA results from loss of the N-terminal helicase domain, not the C terminus.