Refsum disease–associated variations in Fe(II) binding ligands of PHAX (i. e., H175R and D177A/G) (160, 167) were shown to be inactive in vitro (161), which, together with the observations that active site variants of the human 2OG–dependent protein hydroxylase FIH with two protein-bound Fe(II) ligands retain activity (168, 169), suggests that the implications of active site variations in 2OG oxygenases on catalysis have to be considered on a case-to-case basis. The gene discussed is PHAX; the disease is Refsum disease.