ReviewAnnals of the New York Academy of Sciences2015
Diseases caused by mutations in ORAI1 and STIM1.
Review in Annals of the New York Academy of Sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 275 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
275 citing papers in PubMed, 438 citations in OpenAlex.
- Mechanistic insights into Orai dynamics during pore opening.Channels (Austin, Tex.) · 2026Review
- The Diagnostic Journey from Rhabdomyolysis to Myopathy with Tubular Aggregates: A Family-Based Case Report and Review of the Literature.Pediatric reports · 2026Article
- Ryanodine Receptor 1 Is Dispensable for CD4European journal of immunology · 2026Article
- Evolutionarily conserved hydrophobicity and sterics in TM3/TM4 balance Orai1 pore opening.Protein science : a publication of the Protein Society · 2026Article
- Dysregulated calcium signaling underlies hyposalivation and microbial dysbiosis in Down syndrome.Cell reports · 2026Article
- A Quartet of Native Orai Channel Isoforms Orchestrates Graded NFAT Activation and Transcription.bioRxiv : the preprint server for biology · 2026Article
- STIM-Orai signaling in neurons: integrating calcium dynamics and synaptic plasticity.Cell communication and signaling : CCS · 2026Review
- CRAC channels as targets for immunotherapy.Current opinion in immunology · 2026Review
- Unraveling new functions of the Ca2+ sensor STIM1 in cell signaling.Biochemical Society transactions · 2026Review
- STIM/Orai-Mediated Store-Operated CaCells · 2026Review
- Mathematical Modeling of Calcium Dynamics in Ameloblasts.Calcified tissue international · 2026Article
- STIM1 GoF Mutants: Genotype-Phenotype Relationships Across the Stormorken/TAM/YPS Spectrum.Cells · 2026Review
- Bleeding Disorders in Children With Genetic Diseases: A Narrative Review.Acta paediatrica (Oslo, Norway : 1992) · 2026Review
- Mechanosensitive Piezo1 Channels in Enamel Cells.Calcified tissue international · 2026Article
- Exacerbated Skeletal Muscle Phenotype in Mice with 'Homotypic' Expression of the Tubular Aggregate Myopathy ORAI1 G100S Mutation.Biomedicines · 2026Article
- The scramblase anoctamin 9 controls the immune response in lymphocytes.Cellular and molecular life sciences : CMLS · 2026Article
- Structural rearrangements underlying the activation of STIM1 by ER calcium depletion.bioRxiv : the preprint server for biology · 2026Article
- Endocrine Disorders of Calcium Signaling in Children: Neuroendocrine Crosstalk and Clinical Implications.Cells · 2026Review
- Transcellular mitochondrial transfer from hypermetabolic astrocytes to neurons during cocaine and HIV-1 exposure.Cell communication and signaling : CCS · 2025Article
- STIM1 Reduction Prevents Tubular Aggregate Formation and Compromises Muscle Performance in Ageing Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
215 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Ca(2+) release-activated Ca(2+) (CRAC) channels mediate a specific form of Ca(2+) influx called store-operated Ca(2+) entry (SOCE) that contributes to the function of many cell types. CRAC channels are composed of ORAI1 proteins located in the plasma membrane, which form its ion-conducting pore. ORAI1 channels are activated by stromal interaction molecule (STIM) 1 and STIM2 located in the endoplasmic reticulum. Loss- and gain-of-function gene mutations in ORAI1 and STIM1 in human patients cause distinct disease syndromes. CRAC channelopathy is caused by loss-of-function mutations in ORAI1 and STIM1 that abolish CRAC channel function and SOCE; it is characterized by severe combined immunodeficiency (SCID)-like disease, autoimmunity, muscular hypotonia, and ectodermal dysplasia, with defects in sweat gland function and dental enamel formation. The latter defect emphasizes an important role of CRAC channels in tooth development. By contrast, autosomal dominant gain-of-function mutations in ORAI1 and STIM1 result in constitutive CRAC channel activation, SOCE, and increased intracellular Ca(2+) levels that are associated with an overlapping spectrum of diseases, including nonsyndromic tubular aggregate myopathy (TAM) and York platelet and Stormorken syndromes. The latter two syndromes are defined, besides myopathy, by thrombocytopenia, thrombopathy, and bleeding diathesis. The fact that myopathy results from both loss- and gain-of-function mutations in ORAI1 and STIM1 highlights the importance of CRAC channels for Ca(2+) homeostasis in skeletal muscle function. The cellular dysfunction and clinical disease spectrum observed in mutant patients provide important information about the molecular regulation of ORAI1 and STIM1 proteins and the role of CRAC channels in human physiology.
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.