Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
3.1field-weighted citation impact, top 9% of its field
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
3 · Its place in the literature
Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what money
Authors and funding
22 authors at 10 institutions in 4 countries.
Bing ZhangShanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Department of Anesthesiology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, 201204 Shanghai, China.ORCID 0000-0002-3275-5489
Sensen ZhangMinistry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084 Beijing, China.ORCID 0000-0001-8827-3959
Maya M PolovitskayaLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany.ORCID 0000-0002-8144-9824
Jingbo YiMinistry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084 Beijing, China.ORCID 0000-0003-0597-3816
Binglu YeShanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Department of Anesthesiology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, 201204 Shanghai, China.ORCID 0000-0003-4879-5984
Ruochong LiMinistry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084 Beijing, China.ORCID 0000-0001-7372-3267
Xueying HuangShanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Department of Anesthesiology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, 201204 Shanghai, China.ORCID 0000-0002-6934-7788
Jian YinMinistry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084 Beijing, China.ORCID 0000-0002-2251-8674
Sebastian NeuensDepartment of Genetics, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles (ULB), Brussels, Belgium.ORCID 0000-0003-2979-3764
Tom BalfroidDepartment of Pediatric Neurology, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles (ULB), Brussels, Belgium.ORCID 0000-0002-0825-6196
Julie SobletDepartment of Genetics, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles (ULB), Brussels, Belgium.ORCID 0000-0002-3732-2498
Daphné VensPediatric Intensive Care Unit, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles (ULB), Brussels, Belgium.ORCID 0000-0002-7518-2422
Alec AebyDepartment of Pediatric Neurology, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles (ULB), Brussels, Belgium.ORCID 0000-0002-7516-665X
Xiaoling LiWuya College of Innovation, Shenyang Pharmaceutical University, 110016 Shenyang, China.ORCID 0009-0001-6492-2739
Jinjin CaiKey Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203 Shanghai, China.ORCID 0000-0001-7893-7109
Yingcai SongShanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Department of Anesthesiology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, 201204 Shanghai, China.ORCID 0009-0001-5744-9656
Yuanxi LiInstitute for Cognitive Neurodynamics, School of Mathematics, East China University of Science and Technology, 200237 Shanghai, China.ORCID 0000-0002-9170-7022
Marco TartagliaMolecular Genetics and Functional Genomics, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.ORCID 0000-0001-7736-9672
Yang LiKey Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203 Shanghai, China.ORCID 0000-0001-7182-6756
Thomas J JentschLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany.ORCID 0000-0002-3509-2553
Maojun YangMinistry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084 Beijing, China.ORCID 0000-0002-6798-3094
Zhiqiang LiuShanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Department of Anesthesiology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, 201204 Shanghai, China.ORCID 0000-0002-3489-9101
Shanghai First Maternity and Infant Hospital · CNCenter for Life Sciences · CNEast China University of Science and Technology · CNUniversité Libre de Bruxelles · BEMax Delbrück Center · DEQueen Fabiola Children's University Hospital · BEFudan University · CNShanghai Institute of Materia Medica · CNShenyang Pharmaceutical University · CNSouthern University of Science and Technology · CN
Funding
No grant is acknowledged in the PubMed record.
6 · The paper itself
Abstract
ClC-6 is a late endosomal voltage-gated chloride-proton exchanger that is predominantly expressed in the nervous system. Mutated forms of ClC-6 are associated with severe neurological disease. However, the mechanistic role of ClC-6 in normal and pathological states remains largely unknown. Here, we present cryo-EM structures of ClC-6 that guided subsequent functional studies. Previously unrecognized ATP binding to cytosolic ClC-6 domains enhanced ion transport activity. Guided by a disease-causing mutation (p.Y553C), we identified an interaction network formed by Y553/F317/T520 as potential hotspot for disease-causing mutations. This was validated by the identification of a patient with a de novo pathogenic variant p.T520A. Extending these findings, we found contacts between intramembrane helices and connecting loops that modulate the voltage dependence of ClC-6 gating and constitute additional candidate regions for disease-associated gain-of-function mutations. Besides providing insights into the structure, function, and regulation of ClC-6, our work correctly predicts hotspots for
Indexed as
Chloride ChannelsNeurodegenerative DiseasesHumansIon TransportMutationStructure-Activity RelationshipChloride ChannelsCLCN6 protein, human
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.
Molecular basis of ClC-6 function and its impairment in human disease. · full record | Socratic