Evidence map›Paper›PMID 30087448›Full record

ArticleEuropean journal of human genetics : EJHG2018

An MTF1 binding site disrupted by a homozygous variant in the promoter of ATP7B likely causes Wilson Disease.

Heidi I Chen, Karthik A Jagadeesh, Johannes Birgmeier, Aaron M Wenger, Harendra Guturu, Susan Schelley, Jonathan A Bernstein, Gill Bejerano

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

Article in European journal of human genetics : EJHG, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-weighted citation impact, top 21% 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

13 citing papers in PubMed, 21 citations in OpenAlex.

  1. Balancing cellular copper levels via the post-translational regulation of copper transport.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
    Review
  2. Analyses ofHuman mutation · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Missing heritability of Wilson disease: a search for the uncharacterized mutations.Mammalian genome : official journal of the International Mammalian Genome Society · 2023
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Limitations of exome sequencing in detecting rare and undiagnosed diseases.American journal of medical genetics. Part A · 2020
    Article
  12. Article
  13. Article
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

8 authors at 2 institutions in 1 country.

Heidi I ChenDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA.
Karthik A JagadeeshDepartment of Computer Science, Stanford University School of Engineering, Stanford, CA, USA.
Johannes BirgmeierDepartment of Computer Science, Stanford University School of Engineering, Stanford, CA, USA.
Aaron M WengerDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1183-0432
Harendra GuturuDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Susan SchelleyDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-6331-247X
Jonathan A BernsteinDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. jon.bernstein@stanford.edu.
Gill BejeranoDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA. bejerano@stanford.edu.ORCID http://orcid.org/0000-0001-5179-3635
Stanford University · USStanford Medicine · US

Funding

GENETICS TRAINING PROGRAM FOR PHD CANDIDATEST32GM007790 · NIGMS · STANFORD UNIVERSITY · PI BRUNET, ANNE, KINGSLEY, DAVID M · 1985 to 2020
$12.8M
NIGMS NIH HHS T32 GM007790
6 · The paper itself

Abstract

Approximately 2% of the human genome accounts for protein-coding genes, yet most known Mendelian disease-causing variants lie in exons or splice sites. Individuals who symptomatically present with monogenic disorders but do not possess function-altering variants in the protein-coding regions of causative genes may harbor variants in the surrounding gene regulatory domains. We present such a case: a male of Afghani descent was clinically diagnosed with Wilson Disease-a disorder of systemic copper buildup-but was found to have no function-altering coding variants in ATP7B (ENST00000242839.4), the typically causative gene. Our analysis revealed the homozygous variant chr13:g.52,586,149T>C (NC_000013.10, hg19) 676 bp into the ATP7B promoter, which disrupts a metal regulatory transcription factor 1 (MTF1) binding site and diminishes expression of ATP7B in response to copper intake, likely resulting in Wilson Disease. Our approach to identify the causative variant can be generalized to systematically discover function-altering non-coding variants underlying disease and motivates evaluation of gene regulatory variants.

Indexed as

Binding SitesChild, PreschoolCopper-Transporting ATPasesDNA-Binding ProteinsHepatolenticular DegenerationHep G2 CellsHomozygoteHumansMaleMutationPromoter Regions, GeneticProtein BindingTranscription Factor MTF-1Transcription FactorsATP7B protein, humanCopper-Transporting ATPasesDNA-Binding ProteinsTranscription Factor MTF-1Transcription Factors

Identifiers

PMID30087448
PMCPMC6244090
OpenAlexW2887427615

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.