ArticleProceedings of the National Academy of Sciences of the United States of America2017
Achromatopsia mutations target sequential steps of ATF6 activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 59 citations in OpenAlex.
- Multiexon deletion alleles of ATF6 linked to achromatopsia.JCI insight · 2020Trial
- Chemical induction and reversal of photoreceptor dystrophy in retinal organoids.Stem cell reports · 2026Article
- Regulation of the endoplasmic reticulum stress sensor ATF6α through multiple oxidoreductases in the ER.iScience · 2026Article
- Mutations in unfolded protein response regulator ATF6 cause hearing and vision loss syndrome.The Journal of clinical investigation · 2025Article
- A deafness-blindness syndrome results from ATF6-based disruption of the unfolded protein response.The Journal of clinical investigation · 2025Article
- Endoplasmic Reticulum-Mitochondria Crosstalk in Fuchs Endothelial Corneal Dystrophy: Current Status and Future Prospects.International journal of molecular sciences · 2025Review
- Genetic phenotypic characteristics and inheritance patterns of patients with achromatopsia at a large academic institution and a review of the literature and gene therapies.Molecular vision · 2025Review
- Vulnerability of the NrlAdvances in experimental medicine and biology · 2025Article
- Review
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Mitochondria and Endoplasmic Reticulum Stress in Retinal Organoids from Patients with Vision Loss.The American journal of pathology · 2023Article
- Molecular Mechanisms for the Regulation of Nuclear Membrane Integrity.International journal of molecular sciences · 2023Review
- Effects of toxicants on endoplasmic reticulum stress and hepatic cell fate determination.Toxicological research · 2023Review
- Endoplasmic reticulum stress: molecular mechanism and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- High-Efficiency CRISPR/Cas9-Mediated Correction of a Homozygous Mutation in Achromatopsia-Patient-Derived iPSCs.International journal of molecular sciences · 2023Article
- The role of epigenetic changes in the pathology and treatment of inherited retinal diseases.Frontiers in cell and developmental biology · 2023Review
- Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications.Molecular neurodegeneration · 2022Review
- A possible connection between reactive oxygen species and the unfolded protein response in lens development: From insight to foresight.Frontiers in cell and developmental biology · 2022Review
- ATF6 is essential for human cone photoreceptor development.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- ATF6 is required for efficient rhodopsin clearance and retinal homeostasis in the P23H rho retinitis pigmentosa mouse model.Scientific reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
Achromatopsia is an autosomal recessive disorder characterized by cone photoreceptor dysfunction. We recently identified activating transcription factor 6 (ATF6) as a genetic cause of achromatopsia. ATF6 is a key regulator of the unfolded protein response. In response to endoplasmic reticulum (ER) stress, ATF6 migrates from the ER to Golgi to undergo regulated intramembrane proteolysis to release a cytosolic domain containing a basic leucine zipper (bZIP) transcriptional activator. The cleaved ATF6 fragment migrates to the nucleus to transcriptionally up-regulate protein-folding enzymes and chaperones. ATF6 mutations in patients with achromatopsia include missense, nonsense, splice site, and single-nucleotide deletion or duplication changes found across the entire gene. Here, we comprehensively tested the function of achromatopsia-associated ATF6 mutations and found that they group into three distinct molecular pathomechanisms: class 1 ATF6 mutants show impaired ER-to-Golgi trafficking and diminished regulated intramembrane proteolysis and transcriptional activity; class 2 ATF6 mutants bear the entire ATF6 cytosolic domain with fully intact transcriptional activity and constitutive induction of downstream target genes, even in the absence of ER stress; and class 3 ATF6 mutants have complete loss of transcriptional activity because of absent or defective bZIP domains. Primary fibroblasts from patients with class 1 or class 3 ATF6 mutations show increased cell death in response to ER stress. Our findings reveal that human ATF6 mutations interrupt distinct sequential steps of the ATF6 activation mechanism. We suggest that increased susceptibility to ER stress-induced damage during retinal development underlies the pathology of achromatopsia in patients with ATF6 mutations.
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.