ATP6V1B2 encodes a subunit for a vacuolar proton pump ATPase. H+-ATPases consist of three A, three B and two G domains. In a bipolar disorder GWAS28, a P-value of 3.32 × 10−5 was observed in ATP6V1G1, encoding the G subunit of the same cytosolic V1 domain to which ATP6V1B2 contributes and which forms a complex with the transmembrane V0 domain for organelle acidification, critical to some forms of receptor-mediated endocytosis and generation of proton gradients across synaptic vesicle membranes. Modest association to bipolar disorder was also reported in an adjacent gene, SLC18A1 (previously VMAT1), which transports monoamines into synaptic vesicles45. Our signal lies in a distinct LD block within ATP6V1B2, but SLC18A1 could conceivably have regulatory sequences in this upstream region.
