Evidence map›Paper›PMID 26063662›Full record

ArticleHuman genetics2015

Mutation of ATF6 causes autosomal recessive achromatopsia.

Muhammad Ansar, Regie Lyn P Santos-Cortez, Muhammad Arif Nadeem Saqib, Fareeha Zulfiqar, Kwanghyuk Lee, Naeem Mahmood Ashraf, Ehsan Ullah, Xin Wang, Sundus Sajid, Falak Sher Khan and 11 more

Open access · hybridAbstract read
In one paragraph

Article in Human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

52 citing papers in PubMed, 82 citations in OpenAlex.

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  6. Gene Therapy for Achromatopsia.International journal of molecular sciences · 2024
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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

21 authors at 7 institutions in 2 countries.

Muhammad AnsarDepartment of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, 1 Baylor Plaza 700D, Houston, TX, 77030, USA.
Regie Lyn P Santos-Cortez
Muhammad Arif Nadeem Saqib
Fareeha Zulfiqar
Kwanghyuk Lee
Naeem Mahmood Ashraf
Ehsan Ullah
Xin Wang
Sundus Sajid
Falak Sher Khan
Muhammad Amin-ud-Din
University of Washington Center for Mendelian Genomics
Joshua D Smith
Jay Shendure
Michael J Bamshad
Deborah A Nickerson
Abdul Hameed
Saima Riazuddin
Zubair M Ahmed
Wasim Ahmad
Suzanne M Leal
Quaid-i-Azam University · PKUniversity of Washington · USBaylor Genetics · USUniversity of Maryland, Baltimore · USBaylor College of Medicine · USGhazi University · PKInstitute of Biomedical and Genetic Engineering · PK

Funding

UW Center for Mendelian GenomicsU54HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, NICKERSON, DEBORAH A · 2012 to 2015
$20.0M
UW Center for Mendelian GenomicsUM1HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, LEAL, SUZANNE M · 2016 to 2020
$15.3M
Usher Proteins in the Inner Ear Structure and FunctionR01DC012564 · NIDCD · UNIVERSITY OF MARYLAND BALTIMORE · PI Zubair M. Ahmed, Gregory I Frolenkov · 2013 to 2026
$7.0M
Identifying Genes for Non-syndromic Recessive Deafness-A Collaborative StudyR01DC011803 · NIDCD · UNIVERSITY OF MARYLAND BALTIMORE · PI RIAZUDDIN, SAIMA · 2012 to 2016
$1.6M
Molecular Genetics of nonsyndromic Oculocutaneous AlbinismR56AR065483 · NIAMS · UNIVERSITY OF MARYLAND BALTIMORE · PI AHMED, ZUBAIR M. · 2014 to 2015
$666k
NHGRI NIH HHS U54 HG006493NHGRI NIH HHS UM1 HG006493NIAMS NIH HHS R56 AR065483NIDCD NIH HHS R01 DC011803NIDCD NIH HHS R01 DC012564
6 · The paper itself

Abstract

Achromatopsia (ACHM) is an early-onset retinal dystrophy characterized by photophobia, nystagmus, color blindness and severely reduced visual acuity. Currently mutations in five genes CNGA3, CNGB3, GNAT2, PDE6C and PDE6H have been implicated in ACHM. We performed homozygosity mapping and linkage analysis in a consanguineous Pakistani ACHM family and mapped the locus to a 15.12-Mb region on chromosome 1q23.1-q24.3 with a maximum LOD score of 3.6. A DNA sample from an affected family member underwent exome sequencing. Within the ATF6 gene, a single-base insertion variant c.355_356dupG (p.Glu119Glyfs*8) was identified, which completely segregates with the ACHM phenotype within the family. The frameshift variant was absent in public variant databases, in 130 exomes from unrelated Pakistani individuals, and in 235 ethnically matched controls. The variant is predicted to result in a truncated protein that lacks the DNA binding and transmembrane domains and therefore affects the function of ATF6 as a transcription factor that initiates the unfolded protein response during endoplasmic reticulum (ER) stress. Immunolabeling with anti-ATF6 antibodies showed localization throughout the mouse neuronal retina, including retinal pigment epithelium, photoreceptor cells, inner nuclear layer, inner and outer plexiform layers, with a more prominent signal in retinal ganglion cells. In contrast to cytoplasmic expression of wild-type protein, in heterologous cells ATF6 protein with the p.Glu119Glyfs*8 variant is mainly confined to the nucleus. Our results imply that response to ER stress as mediated by the ATF6 pathway is essential for color vision in humans.

Indexed as

Frameshift MutationActivating Transcription Factor 6AdolescentAnimalsAsian PeopleColor Vision DefectsConsanguinityDNA Mutational AnalysisExomeFemaleGenotyping TechniquesHomozygoteHumansLimit of DetectionMaleMiceActivating Transcription Factor 6ATF6 protein, human

Identifiers

PMID26063662
PMCPMC4529463
OpenAlexW1556094842

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.