Biallelic loss-of-function mutations in BPNT1 cause vitamin B12–dependent megaloblastic anemia

ABSTRACT: We identified biallelic loss-of-function BPNT1 mutations in 3 patients with recurrent vitamin B12-dependent megaloblastic anemia. Mechanistically, BPNT1 deficiency caused the accumulation of PAP (3'-phosphoadenosine 5'-phosphate), impaired ribosome biogenesis, and reduced ileal expression of the cubilin/amnionless receptor complex in Bpnt1-null mice.