ArticleAmerican journal of human genetics2019
De Novo Variants Disturbing the Transactivation Capacity of POU3F3 Cause a Characteristic Neurodevelopmental Disorder.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 50 citations in OpenAlex.
- TAL1 is indispensable in ETV2-primed human endothelial cell fate determination.Science advances · 2026Article
- Identification of 5' untranslated region variants in genes involved in neurodevelopmental disorders.Journal of human genetics · 2026Article
- Case Report: First case of paternal mosaicism in Snijders Blok-Fisher syndrome.Frontiers in genetics · 2026Article
- DNA methylation signatures of frailty beyond age: a longitudinal study of female and male mice.bioRxiv : the preprint server for biology · 2025Article
- Rest Induces a Distinct Transcriptional Program in the Nervous System of the ExercisedInternational journal of molecular sciences · 2025Article
- In vivo CRISPR screening identifies POU3F3 as a novel regulator of ferroptosis resistance in hepatocellular carcinoma via retinoic acid signaling.Cell communication and signaling : CCS · 2025Article
- Phosphorylation of POU3F3 Mediated Nuclear Translocation Promotes Proliferation in Non-Small Cell Lung Cancer through Accelerating ATP5PF Transcription and ATP Production.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Metastatic organotropism in small cell lung cancer.bioRxiv : the preprint server for biology · 2025Article
- A subpopulation of cortical neurons altered by mutations in the autism risk gene DDX3X.Biology open · 2025Article
- Article
- Neuroplasticity-related genes correlate with individual differences in distinct phases of oxycodone self-administration in male rats.Neuropharmacology · 2024Article
- Defining cis-regulatory elements and transcription factors that control human cortical interneuron development.iScience · 2024Article
- Fgf, Hh, and pax2a differentially regulate expression of pax5 and pou3f3b in vestibular and auditory maculae in the zebrafish otic vesicle.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- POU3F3-related disorder: Defining the phenotype and expanding the molecular spectrum.Clinical genetics · 2023Article
- Monoallelic intragenic POU3F2 variants lead to neurodevelopmental delay and hyperphagic obesity, confirming the gene's candidacy in 6q16.1 deletions.American journal of human genetics · 2023Article
- Regulatory de novo mutations underlying intellectual disability.Life science alliance · 2023Article
- AFrontiers in pediatrics · 2023Article
- LncRNA PANTR1 is Associated with Poor Prognostic and Suppresses Apoptosis in Glioma.Journal of oncology · 2023Article
- Article
- A Maternally Inherited Rare Case with Chromoanagenesis-Related Complex Chromosomal Rearrangements and De Novo Microdeletions.Diagnostics (Basel, Switzerland) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
39 authors at 16 institutions in 7 countries.
Funding
Abstract
POU3F3, also referred to as Brain-1, is a well-known transcription factor involved in the development of the central nervous system, but it has not previously been associated with a neurodevelopmental disorder. Here, we report the identification of 19 individuals with heterozygous POU3F3 disruptions, most of which are de novo variants. All individuals had developmental delays and/or intellectual disability and impairments in speech and language skills. Thirteen individuals had characteristic low-set, prominent, and/or cupped ears. Brain abnormalities were observed in seven of eleven MRI reports. POU3F3 is an intronless gene, insensitive to nonsense-mediated decay, and 13 individuals carried protein-truncating variants. All truncating variants that we tested in cellular models led to aberrant subcellular localization of the encoded protein. Luciferase assays demonstrated negative effects of these alleles on transcriptional activation of a reporter with a FOXP2-derived binding motif. In addition to the loss-of-function variants, five individuals had missense variants that clustered at specific positions within the functional domains, and one small in-frame deletion was identified. Two missense variants showed reduced transactivation capacity in our assays, whereas one variant displayed gain-of-function effects, suggesting a distinct pathophysiological mechanism. In bioluminescence resonance energy transfer (BRET) interaction assays, all the truncated POU3F3 versions that we tested had significantly impaired dimerization capacities, whereas all missense variants showed unaffected dimerization with wild-type POU3F3. Taken together, our identification and functional cell-based analyses of pathogenic variants in POU3F3, coupled with a clinical characterization, implicate disruptions of this gene in a characteristic neurodevelopmental disorder.
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.