Recurrent mutations in vacuolar ATPase genes and EGR1 in patients with FL. Hotspot mutations were identified in significantly mutated vacuolar ATPase-associated genes: (A) VMA21 (R148* in 4 of 5 mutated patients; ENST00000370361) and (B) ATP6V1B2 (R400Q in 6 of 9 mutated patients; ENST00000276390). (C) BLAST alignment results illustrating highly conserved yeast Vma2p (YBR127C) amino acid residues previously shown to abrogate ATPase catalytic activity when mutated (yellow) are orthologous to amino acid residues altered by mutations in human ATP6V1B2 (ENST00000276390.2) observed in our cohort (magenta). (D) EGR1 mutations observed in this cohort (N = 105), indicated above the protein diagram, were only observed near the N-terminus of the protein (ENST00000239938). EGR1 mutations previously reported for hematopoietic malignancies in COSMIC and selected papers are depicted below the protein diagram.^{8,23,24,68,69}  See supplemental Table 11 for a complete list of V-ATPase complex and EGR1 mutations.