↓ Skip to main content

COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis

Overview of attention for article published in Nature Genetics, April 2015
Altmetric Badge

About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (96th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (60th percentile)

Citations

dimensions_citation
151 Dimensions

Readers on

mendeley
112 Mendeley
citeulike
2 CiteULike
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis
Published in
Nature Genetics, April 2015
DOI 10.1038/ng.3279
Pubmed ID
Authors

Levi B Watkin, Birthe Jessen, Wojciech Wiszniewski, Timothy J Vece, Max Jan, Youbao Sha, Maike Thamsen, Regie L P Santos-Cortez, Kwanghyuk Lee, Tomasz Gambin, Lisa R Forbes, Christopher S Law, Asbjørg Stray-Pedersen, Mickie H Cheng, Emily M Mace, Mark S Anderson, Dongfang Liu, Ling Fung Tang, Sarah K Nicholas, Karen Nahmod, George Makedonas, Debra L Canter, Pui-Yan Kwok, John Hicks, Kirk D Jones, Samantha Penney, Shalini N Jhangiani, Michael D Rosenblum, Sharon D Dell, Michael R Waterfield, Feroz R Papa, Donna M Muzny, Noah Zaitlen, Suzanne M Leal, Claudia Gonzaga-Jauregui, Eric Boerwinkle, N Tony Eissa, Richard A Gibbs, James R Lupski, Jordan S Orange, Anthony K Shum

Abstract

Unbiased genetic studies have uncovered surprising molecular mechanisms in human cellular immunity and autoimmunity. We performed whole-exome sequencing and targeted sequencing in five families with an apparent mendelian syndrome of autoimmunity characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease. We identified four unique deleterious variants in the COPA gene (encoding coatomer subunit α) affecting the same functional domain. Hypothesizing that mutant COPA leads to defective intracellular transport via coat protein complex I (COPI), we show that COPA variants impair binding to proteins targeted for retrograde Golgi-to-ER transport. Additionally, expression of mutant COPA results in ER stress and the upregulation of cytokines priming for a T helper type 17 (TH17) response. Patient-derived CD4(+) T cells also demonstrate significant skewing toward a TH17 phenotype that is implicated in autoimmunity. Our findings uncover an unexpected molecular link between a vesicular transport protein and a syndrome of autoimmunity manifested by lung and joint disease.

Twitter Demographics

The data shown below were collected from the profiles of 26 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 112 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
Unknown 111 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 23 21%
Researcher 17 15%
Student > Master 12 11%
Professor > Associate Professor 10 9%
Other 8 7%
Other 24 21%
Unknown 18 16%
Readers by discipline Count As %
Medicine and Dentistry 27 24%
Agricultural and Biological Sciences 26 23%
Biochemistry, Genetics and Molecular Biology 18 16%
Immunology and Microbiology 7 6%
Computer Science 3 3%
Other 8 7%
Unknown 23 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 48. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 November 2018.
All research outputs
#501,157
of 16,533,785 outputs
Outputs from Nature Genetics
#1,088
of 6,525 outputs
Outputs of similar age
#8,732
of 231,864 outputs
Outputs of similar age from Nature Genetics
#34
of 85 outputs
Altmetric has tracked 16,533,785 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 6,525 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 34.5. This one has done well, scoring higher than 83% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 231,864 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 85 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.