ArticleAmerican journal of human genetics2020
Variants in SCAF4 Cause a Neurodevelopmental Disorder and Are Associated with Impaired mRNA Processing.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Expanding the phenotypic spectrum associated with ZIC1 variants: A neurodevelopmental disorder with and without craniosynostosis.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Heterozygous loss of SRRM1 may be associated with neurodevelopmental phenotypes and anomalies in cell growth and neurite morphology.European journal of human genetics : EJHG · 2026Article
- Conserved protein Seb1 that interacts with RNA polymerase II and RNA is an antipausing transcription elongation factor.RNA (New York, N.Y.) · 2025Article
- Targeting angiopoietin like-2 positive senescent cells improves cognitive impairment in adult male but not female atherosclerotic LDLrGeroScience · 2025Article
- PTAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Functional assays inGenome research · 2025Review
- Further delineation of the SCAF4-associated neurodevelopmental disorder.European journal of human genetics : EJHG · 2025Article
- Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency.HGG advances · 2025Article
- Data-Driven Molecular Typing: A New Frontier in Esophageal Cancer Management.Cancer medicine · 2025Review
- A novel nonsense mutation inFrontiers in genetics · 2025Article
- mvPPT: A Highly Efficient and Sensitive Pathogenicity Prediction Tool for Missense Variants.Genomics, proteomics & bioinformatics · 2023Article
- Comprehensive analysis of omics data identifies relevant gene networks for Attention-Deficit/Hyperactivity Disorder (ADHD).Translational psychiatry · 2022Article
- Short structural variants as informative genetic markers for ALS disease risk and progression.BMC medicine · 2022Article
- Genetic parameters estimation and genome molecular marker identification for gestation length in pigs.Frontiers in genetics · 2022Article
- Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting.Nature communications · 2021Article
- mRNA isoform balance in neuronal development and disease.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
36 authors at 16 institutions in 4 countries.
Funding
Abstract
RNA polymerase II interacts with various other complexes and factors to ensure correct initiation, elongation, and termination of mRNA transcription. One of these proteins is SR-related CTD-associated factor 4 (SCAF4), which is important for correct usage of polyA sites for mRNA termination. Using exome sequencing and international matchmaking, we identified nine likely pathogenic germline variants in SCAF4 including two splice-site and seven truncating variants, all residing in the N-terminal two thirds of the protein. Eight of these variants occurred de novo, and one was inherited. Affected individuals demonstrated a variable neurodevelopmental disorder characterized by mild intellectual disability, seizures, behavioral abnormalities, and various skeletal and structural anomalies. Paired-end RNA sequencing on blood lymphocytes of SCAF4-deficient individuals revealed a broad deregulation of more than 9,000 genes and significant differential splicing of more than 2,900 genes, indicating an important role of SCAF4 in mRNA processing. Knockdown of the SCAF4 ortholog CG4266 in the model organism Drosophila melanogaster resulted in impaired locomotor function, learning, and short-term memory. Furthermore, we observed an increased number of active zones in larval neuromuscular junctions, representing large glutamatergic synapses. These observations indicate a role of CG4266 in nervous system development and function and support the implication of SCAF4 in neurodevelopmental phenotypes. In summary, our data show that heterozygous, likely gene-disrupting variants in SCAF4 are causative for a variable neurodevelopmental disorder associated with impaired mRNA processing.
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