RNF216 and Cerebellar ataxia - hypogonadism: In contrast, two point mutations found in patients with Gordon Holmes syndrome that target the RING2 domain (R751C) or a region very close to the RING2 (R717C) completely abrogated TRIAD3’s catalytic activity (Fig. 1b), comparable to the direct mutation of the catalytic cysteine in RING2, C745A (not disease-related).