ArticleHuman mutation2018
Severe neurocognitive and growth disorders due to variation in THOC2, an essential component of nuclear mRNA export machinery.
Article in Human mutation, 2018. 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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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.
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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.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Carrier screening in the reproductive setting-Are there medical implications for the heterozygote?-A guide for clinicians.Pregnancy (Hoboken, N.J.) · 2026Review
- Unlocking the Future of Hepatocellular Carcinoma Early Diagnosis: The Promise of Extracellular Vesicle Biomarkers.Journal of clinical and translational hepatology · 2026Review
- A Bioinformatics Analysis on the Subtypes of Hepatocellular Carcinoma Related to RNA Processing Genes to Reveal Prognosis and Immune Microenvironment Features.Digestive diseases and sciences · 2025Article
- Developmental and Epileptic Encephalopathies: Need for Bridging the Gaps Between Clinical Syndromes and Underlying Genetic Etiologies.Indian journal of pediatrics · 2025Review
- Compromised transcription-mRNA export factor THOC2 causes R-loop accumulation, DNA damage and adverse neurodevelopment.Nature communications · 2024Article
- Cross-linking mass spectrometric analysis of the endogenous TREX complex fromRNA (New York, N.Y.) · 2023Article
- MiR-30e-3p inhibits gastric cancer development by negatively regulating THO complex 2 and PI3K/AKT/mTOR signaling.World journal of gastrointestinal oncology · 2022Article
- Lessons learnt from multifaceted diagnostic approaches to the first 150 families in Victoria's Undiagnosed Diseases Program.Journal of medical genetics · 2022Article
- Comprehensive analysis of spliceosome genes and their mutants across 27 cancer types in 9070 patients: clinically relevant outcomes in the context of 3P medicine.The EPMA journal · 2022Article
- Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders.Orphanet journal of rare diseases · 2022Article
- Article
- Predictive Models for HCC Prognosis, Recurrence Risk, and Immune Infiltration Based on Two Exosomal Genes:Journal of inflammation research · 2021Article
- Structure of the human core transcription-export complex reveals a hub for multivalent interactions.eLife · 2020Article
- A 2020 View on the Genetics of Developmental and Epileptic Encephalopathies.Epilepsy currents · 2020Article
- Expanding Clinical Presentations Due to Variations in THOC2 mRNA Nuclear Export Factor.Frontiers in molecular neuroscience · 2020Article
- Skewed X-Chromosome Inactivation and Compensatory Upregulation of Escape Genes Precludes Major Clinical Symptoms in a Female With a Large Xq Deletion.Frontiers in genetics · 2020Article
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Authors and funding
32 authors at 17 institutions in 6 countries.
Funding
Abstract
Highly conserved TREX-mediated mRNA export is emerging as a key pathway in neuronal development and differentiation. TREX subunit variants cause neurodevelopmental disorders (NDDs) by interfering with mRNA export from the cell nucleus to the cytoplasm. Previously we implicated four missense variants in the X-linked THOC2 gene in intellectual disability (ID). We now report an additional six affected individuals from five unrelated families with two de novo and three maternally inherited pathogenic or likely pathogenic variants in THOC2 extending the genotypic and phenotypic spectrum. These comprise three rare missense THOC2 variants that affect evolutionarily conserved amino acid residues and reduce protein stability and two with canonical splice-site THOC2 variants that result in C-terminally truncated THOC2 proteins. We present detailed clinical assessment and functional studies on a de novo variant in a female with an epileptic encephalopathy and discuss an additional four families with rare variants in THOC2 with supportive evidence for pathogenicity. Severe neurocognitive features, including movement and seizure disorders, were observed in this cohort. Taken together our data show that even subtle alterations to the canonical molecular pathways such as mRNA export, otherwise essential for cellular life, can be compatible with life, but lead to NDDs in humans.
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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.