A Novel Missense Variant of ZC3H12A in Pulmonary Arterial Hypertension.

BACKGROUND: Because Regnase-1, encoded by ZC3H12A, suppresses the development of pulmonary arterial hypertension (PAH) by controlling pro-inflammatory cytokines, we aimed to identify ZC3H12A variants in patients with PAH. METHODS AND RESULTS: We analyzed whole-genome sequence data of patients with PAH to search for disease-associated ZC3H12A variants. The Regnase-1 p.D426G variant was identified in 2 patients, 1 of whom presented with prominent infiltration of inflammatory cells in the lung. The protein level of the variant was decreased in vitro. CONCLUSIONS: We identified a novel missense variant of ZC3H12A that is directly involved in regulating inflammation in patients with PAH.