ArticleProceedings of the National Academy of Sciences of the United States of America2022
Genome-wide detection of human variants that disrupt intronic branchpoints.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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Who cites it
36 citing papers in PubMed, 46 citations in OpenAlex.
- Genome-wide detection of human 5' UTR variants that impact protein translation.American journal of human genetics · 2026Article
- Genome-wide functional annotation and interpretation of splicing variants: toward RNA-targeted therapies.Journal of human genetics · 2025Review
- A human YEATS4 variant confers resistance to TST and IGRA conversion despite Mycobacterium tuberculosis exposure.Genome medicine · 2025Article
- A basic framework to explain splice-site choice in eukaryotes.Nature communications · 2025Article
- Intronic branchpoint-to-acceptor variants underlying inborn errors of immunity.Journal of human immunity · 2025Article
- Sm-site containing mRNAs can accept Sm-rings and are downregulated in Spinal Muscular Atrophy.Nucleic acids research · 2025Article
- DBR1 orchestrates the fate of lariat RNA: debranching-dependent turnover and function.Nucleic acids research · 2025Review
- Cancer-associated SF3B1 mutation K700E causes widespread changes in U2/branchpoint recognition without altering splicing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Global dysregulation of circular RNAs in frontal cortex and whole blood from DM1 and DM2.Human genetics · 2025Article
- A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity.The Journal of experimental medicine · 2025Article
- Identification of a Rare Branch Point Variant in the SMS Gene in a Large Family With a Severe Form of Snyder-Robinson Syndrome.Clinical genetics · 2025Article
- A novel homozygous intronic variant in CDT1 that alters splicing causes Meier-Gorlin syndrome, and a review of published mutations and growth hormone treatments.Orphanet journal of rare diseases · 2024Review
- African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1.Nature structural & molecular biology · 2024Article
- Cancer-associated SF3B1 mutation K700E causes widespread changes in U2/branchpoint recognition without altering splicing.bioRxiv : the preprint server for biology · 2024Article
- Association Between the rs13306703 and rs8192288 Variants of theDiseases (Basel, Switzerland) · 2024Article
- Mechanistic Insights into Alternative Gene Splicing in Oxidative Stress and Tissue Injury.Antioxidants & redox signaling · 2024Review
- The role of structure in regulatory RNA elements.Bioscience reports · 2024Review
- Sarbecovirus disease susceptibility is conserved across viral and host models.Virus research · 2024Article
- Article
- Human inherited PD-L1 deficiency is clinically and immunologically less severe than PD-1 deficiency.The Journal of experimental medicine · 2024Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 5 countries.
Funding
Abstract
Pre-messenger RNA splicing is initiated with the recognition of a single-nucleotide intronic branchpoint (BP) within a BP motif by spliceosome elements. Forty-eight rare variants in 43 human genes have been reported to alter splicing and cause disease by disrupting BP. However, until now, no computational approach was available to efficiently detect such variants in massively parallel sequencing data. We established a comprehensive human genome-wide BP database by integrating existing BP data and generating new BP data from RNA sequencing of lariat debranching enzyme DBR1-mutated patients and from machine-learning predictions. We characterized multiple features of BP in major and minor introns and found that BP and BP-2 (two nucleotides upstream of BP) positions exhibit a lower rate of variation in human populations and higher evolutionary conservation than the intronic background, while being comparable to the exonic background. We developed BPHunter as a genome-wide computational approach to systematically and efficiently detect intronic variants that may disrupt BP recognition. BPHunter retrospectively identified 40 of the 48 known pathogenic BP variants, in which we summarized a strategy for prioritizing BP variant candidates. The remaining eight variants all create AG-dinucleotides between the BP and acceptor site, which is the likely reason for missplicing. We demonstrated the practical utility of BPHunter prospectively by using it to identify a novel germline heterozygous BP variant of
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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.