Evidence map›Paper›PMID 27974209›Full record

ArticleCell reports2016

TMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammation.

Daniel B Graham, Ariel Lefkovith, Patrick Deelen, Niek de Klein, Mukund Varma, Angela Boroughs, A Nicole Desch, Aylwin C Y Ng, Gaelen Guzman, Monica Schenone and 7 more

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

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

38 citing papers in PubMed, 58 citations in OpenAlex.

  1. Unraveling the Glycosylation Machinery ofInternational journal of molecular sciences · 2026
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  10. Dysregulation of N-glycosylation byInternational journal of biological sciences · 2025
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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

17 authors at 4 institutions in 2 countries.

Daniel B GrahamBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: dgraham@broadinstitute.org.
Ariel LefkovithBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Patrick DeelenDepartment of Genetics, Genomics Coordination Center, University Medical Center Groningen, University Medical Center Groningen, 9713 EX Groningen, the Netherlands.
Niek de KleinDepartment of Genetics, Genomics Coordination Center, University Medical Center Groningen, University Medical Center Groningen, 9713 EX Groningen, the Netherlands.
Mukund VarmaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Angela BoroughsCenter for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
A Nicole DeschBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Aylwin C Y NgGastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Gaelen GuzmanBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Monica SchenoneBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Christine P PetersenBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Atul K BhanPathology Department and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Manuel A RivasBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mark J DalyBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Steven A CarrBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cisca WijmengaDepartment of Genetics, Genomics Coordination Center, University Medical Center Groningen, University Medical Center Groningen, 9713 EX Groningen, the Netherlands.
Ramnik J XavierBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: xavier@molbio.mgh.harvard.edu.
Broad Institute · USHarvard University · USUniversity Medical Center Groningen · NLMassachusetts General Hospital · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Genetic and Pathway Analysis CoreU19AI109725 · NIAID · WASHINGTON UNIVERSITY · PI VIRGIN, HERBERT W · 2014 to 2018
$32.7M
ATG16L1 T300A: genetics to biologyR01DK097485 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI XAVIER, RAMNIK J · 2013 to 2021
$4.1M
NIAID NIH HHS U19 AI109725NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK097485
6 · The paper itself

Abstract

Significant insights into disease pathogenesis have been gleaned from population-level genetic studies; however, many loci associated with complex genetic disease contain numerous genes, and phenotypic associations cannot be assigned unequivocally. In particular, a gene-dense locus on chromosome 11 (61.5-61.65 Mb) has been associated with inflammatory bowel disease, rheumatoid arthritis, and coronary artery disease. Here, we identify TMEM258 within this locus as a central regulator of intestinal inflammation. Strikingly, Tmem258 haploinsufficient mice exhibit severe intestinal inflammation in a model of colitis. At the mechanistic level, we demonstrate that TMEM258 is a required component of the oligosaccharyltransferase complex and is essential for N-linked protein glycosylation. Consequently, homozygous deficiency of Tmem258 in colonic organoids results in unresolved endoplasmic reticulum (ER) stress culminating in apoptosis. Collectively, our results demonstrate that TMEM258 is a central mediator of ER quality control and intestinal homeostasis.

Indexed as

AnimalsApoptosisDisease Models, AnimalEndoplasmic ReticulumEndoplasmic Reticulum StressGlycosylationHexosyltransferasesHumansInflammatory Bowel DiseasesIntestinal MucosaIntestinesMembrane ProteinsMicedolichyl-diphosphooligosaccharide - protein glycotransferaseHexosyltransferasesMembrane ProteinsTMEM258 protein, mouse

Identifiers

PMID27974209
PMCPMC5661940
OpenAlexW2561784502

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.