Of particular interest, the naturally occurring OTUD4 missense variant H148Y (c.442C>T, p.H148Y), identified in pheochromocytomas (34, 35, 36, 37, 38, 39, 40, 41, 42), resides within the catalytically essential His loop of the OTU domain (43, 44, 45), suggesting functional impairment. This evidence concerns the gene OTUD4 and pheochromocytoma.