ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis.
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Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14citing papers in PubMed
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Exploring the role of VAV2 rare variants in primary open-angle glaucoma: genetic insights and pathophysiological mechanisms.Science China. Life sciences · 2026Article
- Adrenomedullin-RAMP2 System Modulates Inflammation and Tissue Repair in Experimental Autoimmune Uveitis Via T-Cell and M2 Macrophage Regulation.Investigative ophthalmology & visual science · 2025Article
- Cross-Tissue Transcriptome-Wide Association Study Identifies Novel Genes Associated With POAG.Investigative ophthalmology & visual science · 2025Article
- Clinical Potential of Adrenomedullin Signaling in the Cardiovascular System.Circulation research · 2023Review
- Cholesterol homeostasis regulated by ABCA1 is critical for retinal ganglion cell survival.Science China. Life sciences · 2023Article
- Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins.Pharmacological reviews · 2023Review
- Asian Race and Primary Open-Angle Glaucoma: Where Do We Stand?Journal of clinical medicine · 2022Review
- Identification of the potential biological target molecules related to primary open-angle glaucoma.BMC ophthalmology · 2022Article
- Catenin α 1 mutations cause familial exudative vitreoretinopathy by overactivating Norrin/β-catenin signaling.The Journal of clinical investigation · 2021Article
- Identification of novel USH2A mutations in patients with autosomal recessive retinitis pigmentosa via targeted next‑generation sequencing.Molecular medicine reports · 2020Article
- Dawn of a New RAMPage.Trends in pharmacological sciences · 2020Review
- Identification of lncRNA-miRNA-mRNA regulatory network associated with primary open angle glaucoma.BMC ophthalmology · 2020Article
- Exome sequencing revealed Notch ligand JAG1 as a novel candidate gene for familial exudative vitreoretinopathy.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Article
- Update on the genetics of primary open-angle glaucoma.Experimental eye research · 2019Review
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Authors and funding
41 authors at 9 institutions in 5 countries.
Bo GongThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Houbin ZhangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Lulin HuangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Yuhong ChenDepartment of Ophthalmology and Visual Science, Eye and Ear Nose Throat (ENT) Hospital, Fudan University, Shanghai, China.
Yi ShiThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Pancy Oi-Sin TamDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Xianjun ZhuThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Yi HuangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Bo LeiPeople's Hospital of Zhengzhou University and Henan Provincial People's Hospital, Henan Eye Institute, Henan Eye Hospital, Zhengzhou, China.
Periasamy SundaresanDepartment of Genetics, Dr. G. Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, India Aravind Hospital, Tamilnadu, India.
Xi LiThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Linxin JiangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Jialiang YangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Ying LinThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Fang LuThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Lijia ChenDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Yuanfeng LiThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Christopher Kai-Shun LeungDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Xiaoxin GuoThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Shanshan ZhangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Guo HuangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Yaqi WuThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Tongdan ZhouThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Ping ShuaiThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Clement Chee-Yung ThamDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Nicole WeisschuhMolecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany.
Subbaiah Ramasamy KrishnadasDepartment of Genetics, Dr. G. Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, India Aravind Hospital, Tamilnadu, India.
Christian MardinDepartment of Ophthalmology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
André ReisInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Jiyun YangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Lin ZhangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Yu ZhouThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Ziyan WangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Chao QuDepartment of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Peter X ShawDepartment of Ophthalmology, University of California San Diego, La Jolla, CA, USA.
Chi-Pui PangDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Xinghuai SunDepartment of Ophthalmology and Visual Science, Eye and Ear Nose Throat (ENT) Hospital, Fudan University, Shanghai, China.
Weiquan ZhuDepartment of Medicine, Program in Molecular Medicine, University of Utah, Salt Lake City, UT, USA.
Dean Yaw LiDepartment of Medicine, Program in Molecular Medicine, University of Utah, Salt Lake City, UT, USA.
Francesca PasuttoInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Zhenglin YangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. zhenglin.yang@hsc.utah.edu.
University of Electronic Science and Technology of China · CNChinese University of Hong Kong · HKFriedrich-Alexander-Universität Erlangen-Nürnberg · DEAravind Eye Hospital · INEye & ENT Hospital of Fudan University · CNUniversity of Utah · USHenan Provincial People's Hospital · CNSTZ eyetrial · DEUniversity of California San Diego · US
Funding
HTRA1 as a Therapeutic Target in the Treatment of Wet AMDR01EY025693 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHAW, PETER X · 2015 to 2019
$1.8MNEI NIH HHS R01 EY025693
Abstract
purposePrimary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and mutations in known genes can only explain 5-6% of POAG. This study was conducted to identify novel POAG-causing genes and explore the pathogenesis of this disease.
methodsExome sequencing was performed in a Han Chinese cohort comprising 398 sporadic cases with POAG and 2010 controls, followed by replication studies by Sanger sequencing. A heterozygous Ramp2 knockout mouse model was generated for in vivo functional study.
resultsUsing exome sequencing analysis and replication studies, we identified pathogenic variants in receptor activity-modifying protein 2 (RAMP2) within three genetically diverse populations (Han Chinese, German, and Indian). Six heterozygous RAMP2 pathogenic variants (Glu39Asp, Glu54Lys, Phe103Ser, Asn113Lysfs*10, Glu143Lys, and Ser171Arg) were identified among 16 of 4763 POAG patients, whereas no variants were detected in any exon of RAMP2 in 10,953 control individuals. Mutant RAMP2s aggregated in transfected cells and resulted in damage to the AM-RAMP2/CRLR-cAMP signaling pathway. Ablation of one Ramp2 allele led to cAMP reduction and retinal ganglion cell death in mice.
conclusionThis study demonstrated that disruption of RAMP2/CRLR-cAMP axis could cause POAG and identified a potential therapeutic intervention for POAG.
Indexed as
AnimalsAsian PeopleCalcitonin Receptor-Like ProteinChinaChlorocebus aethiopsCohort StudiesCOS CellsCyclic AMPExome SequencingGenetic Predisposition to DiseaseGlaucoma, Open-AngleHEK293 CellsHumansMaleMiceMice, KnockoutCalcitonin Receptor-Like ProteinCALCRL protein, humanCyclic AMPRAMP2 protein, humanRamp2 protein, mouseReceptor Activity-Modifying Protein 2exome sequencingheterozygous pathogenic variantprimary open-angle glaucoma (POAG)receptor activity-modifying protein 2 (RAMP2)retinal ganglion cell (RGC)
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