ArticleBrain : a journal of neurology2022
TMEM63C mutations cause mitochondrial morphology defects and underlie hereditary spastic paraplegia.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 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
23 citing papers in PubMed, 35 citations in OpenAlex.
- A TMEM63B variant with enhanced mechanosensitive channel activity and acquired lipid scramblase function.The Journal of general physiology · 2026Article
- Generation and Exosomal Noncoding RNA Profiling of Down Syndrome-Specific Induced Pluripotent Stem Cells.Stem cell reviews and reports · 2026Article
- Lipid Regulation of Mechanosensitive Ion Channels.International journal of molecular sciences · 2026Review
- Mechanosensitive TMEM63 Ion Channels: Structure, Gating Mechanism, and Emerging Physiological and Pathological Roles.Results and problems in cell differentiation · 2026Review
- From plasma membrane to lysosomes: expanding roles of TMEM63/OSCA channels in mechanosensation and intracellular signaling.Frontiers in pharmacology · 2026Review
- Mitochondria-ER contact sites in neurological disorders.Animal cells and systems · 2026Review
- Article
- Cation Channel TMEM63A Autonomously Facilitates Oligodendrocyte Differentiation at an Early Stage.Neuroscience bulletin · 2025Article
- Neurodevelopmental Implications Underpinning Hereditary Spastic Paraplegia.CNS neuroscience & therapeutics · 2025Review
- Wide-ranging cellular functions of ion channels and lipid scramblases in the structurally related TMC, TMEM16 and TMEM63 families.Nature structural & molecular biology · 2025Review
- Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression.Biomarker research · 2025Review
- Article
- Mechanosensitive channels TMEM63A and TMEM63B mediate lung inflation-induced surfactant secretion.The Journal of clinical investigation · 2024Article
- Ethnicity-related differences in mitochondrial regulation by insulin stimulation in diabetes.Journal of cellular physiology · 2024Review
- A comprehensive analysis of spermatozoal RNA elements in idiopathic infertile males undergoing fertility treatment.Scientific reports · 2024Article
- Expression and localization of the mechanosensitive/osmosensitive ion channel TMEM63B in the mouse urinary tract.Physiological reports · 2024Article
- Article
- Drosophila TMEM63 and mouse TMEM63A are lysosomal mechanosensory ion channels.Nature cell biology · 2024Article
- Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in TMEM141, DDHD2, and LHFPL5.Frontiers of medicine · 2024Article
- Multi-omics approach reveals dysregulated genes during hESCs neuronal differentiation exposure to paracetamol.iScience · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
31 authors at 9 institutions in 5 countries.
Funding
Abstract
The hereditary spastic paraplegias (HSP) are among the most genetically diverse of all Mendelian disorders. They comprise a large group of neurodegenerative diseases that may be divided into 'pure HSP' in forms of the disease primarily entailing progressive lower-limb weakness and spasticity, and 'complex HSP' when these features are accompanied by other neurological (or non-neurological) clinical signs. Here, we identified biallelic variants in the transmembrane protein 63C (TMEM63C) gene, encoding a predicted osmosensitive calcium-permeable cation channel, in individuals with hereditary spastic paraplegias associated with mild intellectual disability in some, but not all cases. Biochemical and microscopy analyses revealed that TMEM63C is an endoplasmic reticulum-localized protein, which is particularly enriched at mitochondria-endoplasmic reticulum contact sites. Functional in cellula studies indicate a role for TMEM63C in regulating both endoplasmic reticulum and mitochondrial morphologies. Together, these findings identify autosomal recessive TMEM63C variants as a cause of pure and complex HSP and add to the growing evidence of a fundamental pathomolecular role of perturbed mitochondrial-endoplasmic reticulum dynamics in motor neurone degenerative diseases.
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.