Evidence map›Paper›PMID 23493553›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Gout-causing Q141K mutation in ABCG2 leads to instability of the nucleotide-binding domain and can be corrected with small molecules.

Owen M Woodward, Deepali N Tukaye, Jinming Cui, Patrick Greenwell, Leeza M Constantoulakis, Benjamin S Parker, Anjana Rao, Michael Köttgen, Peter C Maloney, William B Guggino

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 3 pooled it
6.9field-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

63 citing papers in PubMed, 3 syntheses or guidelines pooled it, 106 citations in OpenAlex.

  1. Pooled it
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  14. Review
  15. The Evolving Landscape of Gout in the Female: A Narrative Review.Gout, urate, and crystal deposition disease · 2023
    Article
  16. Cannabis Pharmacogenomics: A Path to Personalized Medicine.Current issues in molecular biology · 2023
    Review
  17. Review
  18. Article
  19. Review
  20. Multidrug efflux transporter ABCG2: expression and regulation.Cellular and molecular life sciences : CMLS · 2021
    Review

3 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

10 authors at 3 institutions in 2 countries.

Owen M WoodwardDepartment of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. owenw@jhmi.edu
Deepali N Tukaye
Jinming Cui
Patrick Greenwell
Leeza M Constantoulakis
Benjamin S Parker
Anjana Rao
Michael Köttgen
Peter C Maloney
William B Guggino
Johns Hopkins Medicine · USJohns Hopkins University · USUniversity Medical Center Freiburg · DE

Funding

MECHANISMS OF TRANSPORT IN PROXIMAL AND DISTAL TUBULESR01DK032753 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI GUGGINO, WILLIAM B. · 1986 to 2011
$3.7M
NIDDK NIH HHS R01 DK032753NIDDK NIH HHS R01DK32753
6 · The paper itself

Abstract

The multidrug ATP-binding cassette, subfamily G, 2 (ABCG2) transporter was recently identified as an important human urate transporter, and a common mutation, a Gln to Lys substitution at position 141 (Q141K), was shown to cause hyperuricemia and gout. The nature of the Q141K defect, however, remains undefined. Here we explore the Q141K ABCG2 mutation using a comparative approach, contrasting it with another disease-causing mutation in an ABC transporter, the deletion of Phe-508 (ΔF508) in the cystic fibrosis transmembrane conductance regulator (CFTR). We found, much like in ΔF508 CFTR, that the Q141K mutation leads to instability in the nucleotide-binding domain (NBD), a defect that translates to significantly decreased protein expression. However, unlike the CFTR mutant, the Q141K mutation does not interfere with the nucleotide-binding domain/intracellular loop interactions. This investigation has also led to the identification of critical residues involved in the protein-protein interactions necessary for the dimerization of ABCG2: Lys-473 (K473) and Phe-142 (F142). Finally, we have demonstrated the utility of using small molecules to correct the Q141K defect in expression and function as a possible therapeutic approach for hyperuricemia and gout.

Indexed as

Mutation, MissenseAmino Acid SubstitutionAnimalsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2CHO CellsCricetinaeCricetulusCystic Fibrosis Transmembrane Conductance RegulatorGoutHEK293 CellsHumansHyperuricemiaNeoplasm ProteinsProtein StabilityProtein Structure, SecondaryABCG2 protein, humanATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2CFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorNeoplasm Proteins

Identifiers

PMID23493553
PMCPMC3612674
OpenAlexW2077197798

What OpenQuestion holds

Textmetadata
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.