ArticlePLoS genetics2017
Human mutations in integrator complex subunits link transcriptome integrity to brain development.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers.
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.
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.
Who cites it
73 citing papers in PubMed, 112 citations in OpenAlex.
- Multiple genomic copy number variants associated with periventricular nodular heterotopia indicate extreme genetic heterogeneity.European journal of human genetics : EJHG · 2019Trial
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- Unprocessed U1 snRNAs as a biomarker of INTS11- and BRAT1-related neurodevelopmental disorders.Genome medicine · 2026Article
- Gene variants in periventricular nodular heterotopia.Acta epileptologica · 2026Review
- Integrator subunit IntS11 orchestrates the temporal dynamics of neural lineage progression in Drosophila.Cell & bioscience · 2026Article
- Integrator 20th anniversary: a molecular machine indispensable in development and disease.Trends in molecular medicine · 2026Review
- Characterizing a Unique Retinal Phenotype in INTS11-Associated Neurodevelopmental Disorder.Investigative ophthalmology & visual science · 2026Article
- Coxsackievirus B3 Cleaves INTS10 Through 3C Protease to Facilitate Its Replication.International journal of molecular sciences · 2026Article
- INTS1 is required for maintaining accurate transcriptional integrity and behavior in zebrafish.NAR genomics and bioinformatics · 2025Article
- Essential function of the integrator complex in Kaposi's sarcoma-associated herpesvirus lytic replication.Journal of virology · 2025Article
- Novel BiallelicGenes · 2025Review
- Mutant alleles of the Caenorhabditis elegans rde-1 gene identified through chemical mutagenesis of an snRNA misprocessing reporter.G3 (Bethesda, Md.) · 2025Article
- Increased burden of rare variants in GWAS associated genes in familial multiple sclerosis.Scientific reports · 2025Article
- Article
- Differential effect of ubiquitous and germline depletion of Integrator complex function on C. elegans physiology.Biology open · 2025Article
- Classification of Brain Magnetic Resonance Imaging Abnormalities and Spectrum of Neurological Findings in a Cohort with Copy Number Variation-Related Disorders.Molecular syndromology · 2025Article
- The enhancer module of Integrator controls cell identity and early neural fate commitment.Nature cell biology · 2025Article
- Fateful Decisions of Where to Cut the Line: Pathology Associated with Aberrant 3' End Processing and Transcription Termination.Journal of molecular biology · 2025Review
- INTS11-related neurodevelopmental disorder: a case report and literature review.Journal of human genetics · 2024Review
- Whole-genome sequencing identifies novel genes for autism in Chinese trios.Science China. Life sciences · 2024Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
Abstract
Integrator is an RNA polymerase II (RNAPII)-associated complex that was recently identified to have a broad role in both RNA processing and transcription regulation. Importantly, its role in human development and disease is so far largely unexplored. Here, we provide evidence that biallelic Integrator Complex Subunit 1 (INTS1) and Subunit 8 (INTS8) gene mutations are associated with rare recessive human neurodevelopmental syndromes. Three unrelated individuals of Dutch ancestry showed the same homozygous truncating INTS1 mutation. Three siblings harboured compound heterozygous INTS8 mutations. Shared features by these six individuals are severe neurodevelopmental delay and a distinctive appearance. The INTS8 family in addition presented with neuronal migration defects (periventricular nodular heterotopia). We show that the first INTS8 mutation, a nine base-pair deletion, leads to a protein that disrupts INT complex stability, while the second missense mutation introduces an alternative splice site leading to an unstable messenger. Cells from patients with INTS8 mutations show increased levels of unprocessed UsnRNA, compatible with the INT function in the 3'-end maturation of UsnRNA, and display significant disruptions in gene expression and RNA processing. Finally, the introduction of the INTS8 deletion mutation in P19 cells using genome editing alters gene expression throughout the course of retinoic acid-induced neural differentiation. Altogether, our results confirm the essential role of Integrator to transcriptome integrity and point to the requirement of the Integrator complex in human brain development.
Indexed as
Identifiers
What OpenQuestion holds
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.