A Novel Missense Variant of ZC3H12A in Pulmonary Arterial Hypertension

Ryotaro Asano; Makoto Okazawa; Tomohiko Ishibashi; Xin Ding; Keiko Ohta-Ogo; Kotaro Akaki; Saori Umeki-Mizushima; Akiko Yamagishi; Tadakatsu Inagaki; Ai Yaku; Shinya Fujisaki; Takatoyo Kiko; Kinta Hatakeyama; Osamu Takeuchi; Takeshi Ogo; Yoshikazu Nakaoka

doi:10.1253/circrep.CR-25-0007

Rapid Communications

A Novel Missense Variant of ZC3H12A in Pulmonary Arterial Hypertension

Ryotaro Asano ^†, Makoto Okazawa ^†, Tomohiko Ishibashi ^†, Xin Ding, Keiko Ohta-Ogo, Kotaro Akaki, Saori Umeki-Mizushima, Akiko Yamagishi, Tadakatsu Inagaki, Ai Yaku, Shinya Fujisaki, Takatoyo Kiko, Kinta Hatakeyama, Osamu Takeuchi, Takeshi Ogo, Yoshikazu Nakaoka

Author information

Ryotaro Asano ^†
Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute [Japan]
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center Hospital [Japan]
Makoto Okazawa ^†
Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute [Japan]
Tomohiko Ishibashi ^†
Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute [Japan]
Xin Ding
Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute [Japan]
Keiko Ohta-Ogo
Department of Pathology, National Cerebral and Cardiovascular Center Hospital [Japan]
Kotaro Akaki
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University [Japan]
Saori Umeki-Mizushima
Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute [Japan]
Akiko Yamagishi
Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute [Japan]
Tadakatsu Inagaki
Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute [Japan]
Ai Yaku
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University [Japan]
Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University [Japan]
Shinya Fujisaki
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center Hospital [Japan]
Takatoyo Kiko
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center Hospital [Japan]
Kinta Hatakeyama
Department of Pathology, National Cerebral and Cardiovascular Center Hospital [Japan]
Osamu Takeuchi
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University [Japan]
Takeshi Ogo
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center Hospital [Japan]
Yoshikazu Nakaoka Corresponding author
Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute [Japan]
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center Hospital [Japan]
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine [Japan]
Department of Molecular Imaging in Cardiovascular Medicine, Osaka University Graduate School of Medicine [Japan]
Author contributions

†These authors contributed equally: Ryotaro Asano, Makoto Okazawa, Tomohiko Ishibashi

Keywords: Genetics, Inflammation, Pulmonary arterial hypertension

JOURNAL OPEN ACCESS FULL-TEXT HTML

2025 Volume 7 Issue 3 Pages 207-211

DOI https://doi.org/10.1253/circrep.CR-25-0007

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Abstract

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.

Corresponding author

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