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. The gene discussed is OTUD4; the disease is hereditary pheochromocytoma-paraganglioma.