ArticleAmerican journal of human genetics2023
Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration.
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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.
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.
Who cites it
31 citing papers in PubMed, 39 citations in OpenAlex.
- Lipid flip-flop in biological membranes: through the lens of TMEM16F.Physiological reviews · 2026Review
- A TMEM63B variant with enhanced mechanosensitive channel activity and acquired lipid scramblase function.The Journal of general physiology · 2026Article
- Ion transport as a determinant of membrane fusion and fission.Nature structural & molecular biology · 2026Review
- Bi-allelic loss-of-function variants in TMEM63B cause syndromic surfactant dysfunction disorder.American journal of human genetics · 2026Article
- TMEM63B regulates nucleocytoplasmic transport and placental development.Nature communications · 2026Article
- Movement Disorders in Developmental and Epileptic Encephalopathies.Movement disorders clinical practice · 2026Review
- Lipid Regulation of Mechanosensitive Ion Channels.International journal of molecular sciences · 2026Review
- International Mouse Phenotyping Consortium Portal: facilitating investigation of gene function and providing insights into human disease.Nucleic acids research · 2026Article
- Telethon Undiagnosed Disease Program: Structured approach to solving rare childhood-onset genetic diseases.Genetics in medicine open · 2026Article
- From plasma membrane to lysosomes: expanding roles of TMEM63/OSCA channels in mechanosensation and intracellular signaling.Frontiers in pharmacology · 2026Review
- Targeting Tmem63b and Piezo2 in C-fiber low-threshold mechanoreceptors: Limitation of Vglut3-IRES-Cre.Biophysical journal · 2025Article
- International Mouse Phenotyping Consortium: Investigating gene function and providing insights into human disease.bioRxiv : the preprint server for biology · 2025Article
- Pathophysiological Mechanisms Fostering Developmental and Epileptic Encephalopathies (DEE): a Complex Interplay between Genetics, Inflammation and Neurodegeneration.Current neurology and neuroscience reports · 2025Review
- Article
- Genetic Insights into Brain Morphology: a Genome-Wide Association Study of Cortical Thickness and TNeuroinformatics · 2025Article
- Mechanical signaling through membrane tension induces somal translocation during neuronal migration.The EMBO journal · 2025Article
- Wide-ranging cellular functions of ion channels and lipid scramblases in the structurally related TMC, TMEM16 and TMEM63 families.Nature structural & molecular biology · 2025Review
- TMEM63B scrambles phospholipids in response to changes in membrane structure.Nature structural & molecular biology · 2025Article
- Membrane structure-responsive lipid scrambling by TMEM63B to control plasma membrane lipid distribution.Nature structural & molecular biology · 2025Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
47 authors at 20 institutions in 10 countries.
Funding
Abstract
By converting physical forces into electrical signals or triggering intracellular cascades, stretch-activated ion channels allow the cell to respond to osmotic and mechanical stress. Knowledge of the pathophysiological mechanisms underlying associations of stretch-activated ion channels with human disease is limited. Here, we describe 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment associated with progressive neurodegenerative brain changes carrying ten distinct heterozygous variants of TMEM63B, encoding for a highly conserved stretch-activated ion channel. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense, including the recurrent p.Val44Met in 7/17 individuals, or in-frame, all affecting conserved residues located in transmembrane regions of the protein. In 12 individuals, hematological abnormalities co-occurred, such as macrocytosis and hemolysis, requiring blood transfusions in some. We modeled six variants (p.Val44Met, p.Arg433His, p.Thr481Asn, p.Gly580Ser, p.Arg660Thr, and p.Phe697Leu), each affecting a distinct transmembrane domain of the channel, in transfected Neuro2a cells and demonstrated inward leak cation currents across the mutated channel even in isotonic conditions, while the response to hypo-osmotic challenge was impaired, as were the Ca
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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 OpenQuestion graph.