Evidence map›Paper›PMID 30057031›Full record

ArticleAmerican journal of human genetics2018

IRF2BPL Is Associated with Neurological Phenotypes.

Paul C Marcogliese, Vandana Shashi, Rebecca C Spillmann, Nicholas Stong, Jill A Rosenfeld, Mary Kay Koenig, Julián A Martínez-Agosto, Matthew Herzog, Agnes H Chen, Patricia I Dickson and 35 more

Erratum issued Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
5.3field-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.

NCT02450851 recruitingnot on this map

Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network

TypeobservationalSponsorNational Human Genome Research Institute (NHGRI)Ran2015 to 2028Enrolled20,000ConditionsGenetic Disease
3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Age and the Diurnal Oscillatory Features of the Human Chronobiome.medRxiv : the preprint server for health sciences · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Excess Wnt in neurological disease.The Biochemical journal · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Exome/Genome Sequencing in Undiagnosed Syndromes.Annual review of medicine · 2023
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

45 authors at 15 institutions in 2 countries.

Paul C MarcoglieseDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Vandana ShashiDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
Rebecca C SpillmannDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
Nicholas StongInstitute for Genomic Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Mary Kay KoenigDivision of Child & Adolescent Neurology, Department of Pediatrics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Julián A Martínez-AgostoDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Child and Adolescent Psychiatry, Resnick Neuropsychiatric Hospital, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Matthew HerzogDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Agnes H ChenDepartment of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Patricia I DicksonDepartment of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Henry J LinDepartment of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Moin U VeraDepartment of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Noriko SalamonDepartment of Radiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
John M GrahamDepartment of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Damara OrtizChildren's Hospital of Pittsburgh, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA 15224, USA.
Elena InfanteChildren's Hospital of Pittsburgh, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA 15224, USA.
Wouter SteyaertDepartment of Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium.
Bart DermautDepartment of Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium.
Bruce PoppeDepartment of Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium.
Hyung-Lok ChungDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Zhongyuan ZuoDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Pei-Tseng LeeDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Oguz KancaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Fan XiaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Yaping YangDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Edward C SmithDivision of Neurology, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
Joan JasienDivision of Neurology, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
Sujay KansagraDivision of Neurology, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
Gail SpiridigliozziDepartment of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC 27710, USA.
Mays El-DairiDepartment of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA.
Robert LarkDepartment of Orthopedic Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
Kacie RileyDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
Dwight D KoeberlDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
Katie Golden-GrantDivision of Genetic Medicine, Seattle Children's Hospital, Seattle, WA 98105, USA.
Program for Undiagnosed Diseases (UD-PrOZA)
Undiagnosed Diseases Network
Shinya YamamotoDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Michael F WanglerDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
Ghayda MirzaaCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98105, USA; Department of Pediatrics, University of Washington, Seattle, WA 98105, USA.
Dimitri HemelsoetDepartment of Neurology, Ghent University Hospital, 9000 Ghent, Belgium.
Brendan LeeDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Stanley F NelsonDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
David B GoldsteinInstitute for Genomic Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Hugo J BellenDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: hbellen@bcm.edu.
Loren D M PenaDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: loren.pena@cchmc.org.
Duke University · USBaylor College of Medicine · USUniversity of California, Los Angeles · USGhent University Hospital · BEColumbia University Irving Medical Center · USUCLA Medical Center · USSeattle Children's Hospital · USChildren's Hospital of Pittsburgh · USHarbor–UCLA Medical Center · USHoward Hughes Medical Institute · USTexas Children's Hospital · USThe Lundquist Institute · USThe University of Texas Health Science Center at Houston · USUniversity of Pittsburgh Medical Center · USUniversity of Washington · US

Funding

Transposon induced disruption of most Drosophila genesR01GM067858 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J · 2003 to 2020
$15.7M
An integrated and diverse genomic medicine program for undiagnosed diseasesU01HG007672 · NHGRI · DUKE UNIVERSITY · PI SHASHI, VANDANA · 2014 to 2022
$13.4M
UCLA clinical site for the investigation of undiagnosed disordersU01HG007703 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARTINEZ-AGOSTO, JULIAN, NELSON, STANLEY F. · 2014 to 2022
$10.1M
Steps towards a paternal gene activation therapy for Angelman syndromeU54HD083092 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI NELSON, DAVID LOREN, SAMACO, RODNEY C · 2014 to 2019
$7.8M
Zebrafish CoreU54NS093793 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J · 2015 to 2022
$7.5M
Expansion and characterization of the Drosophila Toolkit to study SARS-CoV-2R24OD022005 · OD · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J · 2016 to 2023
$7.4M
Genomic medicine and gene function implementation for an underserved populationR01HG011795 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J, WANGLER, MICHAEL FRANCIS · 2021 to 2025
$4.8M
Genes and pathways underlying brain overgrowth and focal cortical malformationsK08NS092898 · NINDS · SEATTLE CHILDREN'S HOSPITAL · PI MIRZAA, GHAYDA · 2015 to 2019
$930k
NHGRI NIH HHS R01 HG011795NHGRI NIH HHS U01 HG007672NHGRI NIH HHS U01 HG007703NICHD NIH HHS U54 HD083092NIGMS NIH HHS R01 GM067858NIH HHS R24 OD022005NINDS NIH HHS K08 NS092898NINDS NIH HHS U54 NS093793
6 · The paper itself

Abstract

Interferon regulatory factor 2 binding protein-like (IRF2BPL) encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals who carry damaging heterozygous variants in IRF2BPL and are affected with neurological symptoms. Five individuals who carry IRF2BPL nonsense variants resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The IRF2BPL bioinformatics signature based on population genomics is consistent with a gene that is intolerant to variation. We show that the fruit-fly IRF2BPL ortholog, called pits (protein interacting with Ttk69 and Sin3A), is broadly detected, including in the nervous system. Complete loss of pits is lethal early in development, whereas partial knockdown with RNA interference in neurons leads to neurodegeneration, revealing a requirement for this gene in proper neuronal function and maintenance. The identified IRF2BPL nonsense variants behave as severe loss-of-function alleles in this model organism, and ectopic expression of the missense variants leads to a range of phenotypes. Taken together, our results show that IRF2BPL and pits are required in the nervous system in humans and flies, and their loss leads to a range of neurological phenotypes in both species.

Indexed as

ataxiaC3HC4 RING fingerCG11138developmental regressionDrosophilaEAP1hypotonianeurodegenerationpitsseizures

Identifiers

PMID30057031
PMCPMC6081494
OpenAlexW2884331585

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.