ArticleHuman mutation2020
Loss of RAD9B impairs early neural development and contributes to the risk for human spina bifida.
Article in Human mutation, 2020. 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 15 papers.
What it found
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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.
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
15 citing papers in PubMed, 19 citations in OpenAlex.
- hiPSC-derived Organoids and Organ-on-chip Systems: New Frontiers in Neural Tube Defect Research.Stem cell reviews and reports · 2026Review
- Spina bifida as a multifactorial birth defect: Risk factors and genetic underpinnings.Pediatric discovery · 2025Review
- Genome-wide analysis of spina bifida risk variants in a case-control study from Bangladesh.Birth defects research · 2024Article
- Bayesian polygenic risk estimation approach to nuclear families with discordant sib-pairs for myelomeningocele.PloS one · 2024Article
- Article
- A Shared Pathogenic Mechanism for Valproic Acid and SHROOM3 Knockout in a Brain Organoid Model of Neural Tube Defects.bioRxiv : the preprint server for biology · 2023Article
- Progress in Modeling Neural Tube Development and Defects by Organoid Reconstruction.Neuroscience bulletin · 2022Review
- Environmental risks of disposable face masks during the pandemic of COVID-19: Challenges and management.The Science of the total environment · 2022Review
- Overview of Neural Tube Defects: Gene-Environment Interactions, Preventative Approaches and Future Perspectives.Biomedicines · 2022Review
- Advantages of CRISPR-Cas9 combined organoid model in the study of congenital nervous system malformations.Frontiers in bioengineering and biotechnology · 2022Review
- Unraveling the complex genetics of neural tube defects: From biological models to human genomics and back.Genesis (New York, N.Y. : 2000) · 2021Review
- Micronutrient imbalance and common phenotypes in neural tube defects.Genesis (New York, N.Y. : 2000) · 2021Review
- Identification of the Key Regulators of Spina Bifida Through Graph-Theoretical Approach.Frontiers in genetics · 2021Article
- FKBP8 variants are risk factors for spina bifida.Human molecular genetics · 2020Article
- Closing in on Mechanisms of Open Neural Tube Defects.Trends in neurosciences · 2020Review
Corrections and comments
- Erratum issuedCorrigendum.2021
Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
DNA damage response (DDR) genes orchestrating the network of DNA repair, cell cycle control, are essential for the rapid proliferation of neural progenitor cells. To date, the potential association between specific DDR genes and the risk of human neural tube defects (NTDs) has not been investigated. Using whole-genome sequencing and targeted sequencing, we identified significant enrichment of rare deleterious RAD9B variants in spina bifida cases compared to controls (8/409 vs. 0/298; p = .0241). Among the eight identified variants, the two frameshift mutants and p.Gln146Glu affected RAD9B nuclear localization. The two frameshift mutants also decreased the protein level of RAD9B. p.Ser354Gly, as well as the two frameshifts, affected the cell proliferation rate. Finally, p.Ser354Gly, p.Ser10Gly, p.Ile112Met, p.Gln146Glu, and the two frameshift variants showed a decreased ability for activating JNK phosphorylation. RAD9B knockdowns in human embryonic stem cells profoundly affected early differentiation through impairing PAX6 and OCT4 expression. RAD9B deficiency impeded in vitro formation of neural organoids, a 3D cell culture model for human neural development. Furthermore, the RNA-seq data revealed that loss of RAD9B dysregulates cell adhesion genes during organoid formation. These results represent the first demonstration of a DDR gene as an NTD risk factor in humans.
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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.