Evidence map›Paper›PMID 27889058›Full record

ArticleAmerican journal of human genetics2016

Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa.

Gavin Arno, Smriti A Agrawal, Aiden Eblimit, James Bellingham, Mingchu Xu, Feng Wang, Christina Chakarova, David A Parfitt, Amelia Lane, Thomas Burgoyne and 20 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
8.9field-weighted citation impact, top 2% 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

87 citing papers in PubMed, 130 citations in OpenAlex.

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  12. Dystonia (Lausanne, Switzerland) · 2024
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  13. Review
  14. Alternative RNA Splicing in the Retina: Insights and Perspectives.Cold Spring Harbor perspectives in medicine · 2023
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  15. Novel pathogenic3 Biotech · 2023
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  17. Modeling Retinitis Pigmentosa with Patient-Derived iPSCs.Advances in experimental medicine and biology · 2023
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27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

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

30 authors at 7 institutions in 3 countries.

Gavin ArnoUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK; Moorfields Eye Hospital, London EC1V 2PD, UK.
Smriti A AgrawalDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3411, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030-3411, USA.
Aiden EblimitDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3411, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030-3411, USA.
James BellinghamUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
Mingchu XuDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3411, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030-3411, USA.
Feng WangDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3411, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030-3411, USA.
Christina ChakarovaUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
David A ParfittUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
Amelia LaneUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
Thomas BurgoyneUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
Sarah HullUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK; Moorfields Eye Hospital, London EC1V 2PD, UK.
Keren J CarssNIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK; Department of Haematology, University of Cambridge, NHS Blood and Transplant Centre, Cambridge CB2 0PT, UK.
Alessia FiorentinoUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
Matthew J HayesUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
Peter M MunroUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
Ralph NicolsDepartment of Ophthalmology, Baylor College of Medicine, Houston, TX 77030-3411, USA.
Nikolas PontikosUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
Graham E HolderUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK; Moorfields Eye Hospital, London EC1V 2PD, UK.
UKIRDC
Chinwe AsomughaDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030-3411, USA.
F Lucy RaymondNIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK; Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
Anthony T MooreUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK; Moorfields Eye Hospital, London EC1V 2PD, UK; Ophthalmology Department, UCSF School of Medicine, Koret Vision Center, San Francisco, CA 94133-0644, USA.
Vincent PlagnolUCL Genetics Institute, University College London, London WC1E 6BT, UK.
Michel MichaelidesUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK; Moorfields Eye Hospital, London EC1V 2PD, UK.
Alison J HardcastleUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
Yumei LiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3411, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030-3411, USA.
Catherine CukrasNational Eye Institute, NIH, Bethesda, MD 20892, USA.
Andrew R WebsterUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK; Moorfields Eye Hospital, London EC1V 2PD, UK.
Michael E CheethamUCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK. Electronic address: michael.cheetham@ucl.ac.uk.
Rui ChenDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3411, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030-3411, USA. Electronic address: ruichen@bcm.edu.
University College London · GBMoorfields Eye Hospital NHS Foundation Trust · GBBaylor College of Medicine · USInstitute of Ophthalmology · MXNational Eye Institute · USNHS Blood and Transplant · GBUniversity of Cambridge · GB

Funding

VISION RESEARCH CENTERP30EY002520 · NEI · BAYLOR COLLEGE OF MEDICINE · PI Samuel M Wu · 1985 to 2026
$14.8M
GENETICS OF EARLY ONSET RETINAL DISEASESR01EY018571 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI RUI CHEN · 2008 to 2026
$7.2M
Molecular Basis of Human Visual System DisordersR01EY022356 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI RUI CHEN · 2012 to 2026
$6.1M
Molecular Mechanisms of Human Retinal DiseaseR01EY020540 · NEI · BAYLOR COLLEGE OF MEDICINE · PI CHEN, RUI, MARDON, GRAEME · 2011 to 2017
$2.3M
Medical Research Council MC_PC_15018NEI NIH HHS P30 EY002520NEI NIH HHS R01 EY018571NEI NIH HHS R01 EY020540NEI NIH HHS R01 EY022356Wellcome Trust
6 · The paper itself

Abstract

Retinitis pigmentosa (RP) is the most frequent form of inherited retinal dystrophy. RP is genetically heterogeneous and the genes identified to date encode proteins involved in a wide range of functional pathways, including photoreceptor development, phototransduction, the retinoid cycle, cilia, and outer segment development. Here we report the identification of biallelic mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals with autosomal-recessive RP from five unrelated families. REEP6 is a member of the REEP/Yop1 family of proteins that influence the structure of the endoplasmic reticulum but is relatively unstudied. The six variants identified include three frameshift variants, two missense variants, and a genomic rearrangement that disrupts exon 1. Human 3D organoid optic cups were used to investigate REEP6 expression and confirmed the expression of a retina-specific isoform REEP6.1, which is specifically affected by one of the frameshift mutations. Expression of the two missense variants (c.383C>T [p.Pro128Leu] and c.404T>C [p.Leu135Pro]) and the REEP6.1 frameshift mutant in cultured cells suggest that these changes destabilize the protein. Furthermore, CRISPR-Cas9-mediated gene editing was used to produce Reep6 knock-in mice with the p.Leu135Pro RP-associated variant identified in one RP-affected individual. The homozygous knock-in mice mimic the clinical phenotypes of RP, including progressive photoreceptor degeneration and dysfunction of the rod photoreceptors. Therefore, our study implicates REEP6 in retinal homeostasis and highlights a pathway previously uncharacterized in retinal dystrophy.

Indexed as

AdolescentAllelesAnimalsChildChild, PreschoolEye ProteinsFemaleGenes, RecessiveHumansInduced Pluripotent Stem CellsMaleMembrane ProteinsMembrane Transport ProteinsMiceMutationMutation, MissenseEye ProteinsMembrane ProteinsMembrane Transport ProteinsREEP6 protein, humanREEP6 protein, mouse

Identifiers

PMID27889058
PMCPMC5142109
OpenAlexW2551680432

What OpenQuestion holds

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Registered trials

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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.